Evaluate Safety, Tolerability, Pharmacokinetics and Immunogenicity of MEDI7352 in Healthy Volunteers

Study identifier:D5680C00004

ClinicalTrials.gov identifier:N/A

EudraCT identifier:2020-005982-14

CTIS identifier:N/A

Study Complete

Official Title

A Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Multiple Doses of MEDI7352 Administered by the Subcutaneous Route in Healthy Japanese and Caucasian Subjects

Medical condition

Painful osteoarthritis of the knee

Phase

Phase 1

Healthy volunteers

Yes

Study drug

MEDI7352, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 20 Apr 2021

Primary Completion Date: 02 Dec 2021

Study Completion Date: 02 Dec 2021

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

• Healthy male or female of non childbearing potential participants aged 18 to 65 (inclusive) years for Caucasian participants and 20 to 65 (inclusive) years for Japanese participants with suitable veins for cannulation or repeated venepuncture
• Japanese or Caucasian ethnicity
• Post-menopausal women must have had ≥ 12 months of spontaneous amenorrhea with an follicle stimulating hormone (FSH) concentration consistently ≥ 40 mIU/mL and a negative serum or urine pregnancy test result at Screening or Day -1. Surgically sterile women must have had a hysterectomy, and bilateral ovariectomy (oophorectomy), must provide documentation of the procedure and have had a negative serum or urine pregnancy test at Screening or Day -1. An intermediate or positive pregnancy test, can be confirmed by repeating the pregnancy test and
demonstrating non-doubling of β-human chorionic gonadotropin levels every 48 to 72 hours
• Men who are biologically capable of fathering children must agree and
commit to use of an adequate form of a highly effective method of
contraception and refrain from sperm donation for the duration of the
Treatment Period and for 3 months after the last administration of study
treatment
• Body mass index 18 and 30 kg/m^2, weight at least 50 kg
• No clinically significant abnormality identified on medical or laboratory
evaluation at Screening unless the Investigator considers that the
finding will not introduce additional risk factors and will not interfere
with the study procedures
• 12-lead electrocardiogram recorded at Screening and Day -1 that is normal for the age group and shows no significant abnormalities that will compromise safety
• Physical examinations with no significant findings at Screening and on
Day -1.

Exclusion Criteria

• Participation in another clinical study or use of any experimental
medication, device, or biologic with an investigational product (IP) within 5 half-lives of that IP or 3 months (whichever is longer) prior to first dosing
• Participation in another study investigating any form of anti-NGF or anti-TNF therapy in the 6 months prior to Screening and until after the final Follow-up Visit
• Any positive laboratory result at screening for COVID-19
• Blood donation or draw in excess of 400 mL within 2 months prior to Screening or plasma donation in excess of 50 mL within 30 prior to Screening
• Inability to comply with study-related restrictions and requirements related to consumption of alcohol, provision of meals and snacks, nicotine use, activity, blood donation, and contraception
• History of severe allergy/hypersensitivity reactions or ongoing severe
allergy/hypersensitivity reactions, or history of hypersensitivity to immunizations or immunoglobulins or other biological modalities
• History of any significant psychiatric disorder
• Any clinically significant illness, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, GI, urologic, immunologic, rheumatologic or endocrine disease or disorder
• Recent (within the last 3 months) or active infection considered to be clinically significant, or any infection for which there are unresolved medical sequelae
• Clinically significant osteoarthritis (OA) currently affecting a major
joint in the upper or lower extremity or axial spine; or other degenerative disease affecting any joint in participants for whom, there is an identified risk of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy; or history of trauma or surgery involving any major joint or axial spine
• Radiological significant abnormalities reported on baseline MRI of hips and knees that are considered to present a risk of osteonecrosis, rapidly progressive OA, subchondral insufficiency fractures; or other coincidental finding(s) that present a risk to the safety or welfare of the participant
• History of excessive alcohol intake
• History of cancer within 5 years, with the exception of non-metastatic basal cell carcinoma of the skin, carcinoma in situ of the cervix or non-progressive prostate cancer
• History of drug abuse or positive test for drugs of abuse or alcohol
• Use of prescription or non-prescription drugs, including vitamins and
herbal and dietary supplements, within 7 days or 5 half-lives of the drug (whichever is longer) prior to the administration of study treatment
• Any clinically important or significant abnormality on a physical examination, vital signs, ECG or clinical laboratory test results that could be detrimental to participant safety or compromise the study
• Positive serologic findings at Screening for Human immunodeficiency
virus antibodies, hepatitis B surface antigen or hepatitis C virus antibodies
• Positive QuantiFERON test for tuberculosis
• Any minor medical or surgical procedure or trauma within 28 days of Day 1 or planned surgical procedure during the study.

Location

Research Site

Harrow, United Kingdom, HA1 3UJ

Arms	Assigned Interventions
Experimental: Cohort 1: Japanese MEDI7352 Randomized Japanese participants will receive single doses of MEDI7352 subcutaneously.	Drug: MEDI7352 A dose of MEDI7352 will be administered as two 1.5 mL injections in the abdomen. Following an overnight fast of at least 8 hours, each participant will receive a single dose of MEDI7352 on 4 occasions.
Placebo Comparator: Cohort 1: Japanese Placebo Randomized Japanese participants will receive matching placebo subcutaneously.	Drug: Placebo Matching placebo will be administered as two 1.5 mL injections in the abdomen. To maintain the double-blind requirements, the placebo volume administered will be equivalent to the MEDI7352 volume administered for each dosing. Following an overnight fast of at least 8 hours, each participant will receive matching placebo on 4 occasions.
Experimental: Cohort 2: Caucasian MEDI7352 Randomized Caucasian participants will receive single doses of MEDI7352 subcutaneously.	Drug: MEDI7352 A dose of MEDI7352 will be administered as two 1.5 mL injections in the abdomen. Following an overnight fast of at least 8 hours, each participant will receive a single dose of MEDI7352 on 4 occasions.
Placebo Comparator: Cohort 2: Caucasian Placebo Randomized Caucasian participants will receive matching placebo subcutaneously.	Drug: Placebo Matching placebo will be administered as two 1.5 mL injections in the abdomen. To maintain the double-blind requirements, the placebo volume administered will be equivalent to the MEDI7352 volume administered for each dosing. Following an overnight fast of at least 8 hours, each participant will receive matching placebo on 4 occasions.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted in 24 Healthy Japanese and Caucasian participants at Parexel Early Phase Clinical Unit London from 20 April 2021 (first subject first visit) to 02 December 2021 (last subject last visit).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The screening period was of 36 days. All the study assessments were performed as per the schedule of assessment. Two cohorts of Japanese (10 participants) and Caucasian (14 participants) participants were enrolled. Participants in each cohort were randomized to receive MEDI7352 or placebo in a ratio of 7:3, respectively.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Participant Flow: Overall Study

	Japanese- MEDI7352	Japanese- Placebo	Caucasian- MEDI7352	Caucasian- Placebo
STARTED	7	3	10	4
COMPLETED	6	3	7	3
NOT COMPLETED	1	0	3	1
Withdrawal by Subject	1	0	1	0
Protocol Violation	0	0	1	1
Adverse Event	0	0	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The Randomised Set will consist of all participants randomised into the study.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Baseline Measures

	Japanese- MEDI7352	Japanese- Placebo	Caucasian- MEDI7352	Caucasian- Placebo	Total
Number of Participants [units: Participants]	7	3	10	4	24
Age, Customized [units: Participants]
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	7	3	10	4	24
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Sex: Female, Male [units: Participants]
Female	0	0	1	0	1
Male	7	3	9	4	23
Age Continuous [units: Years] Mean ± Standard Deviation	34.6 ± 8.3	NA ± NA ^[1]	36.6 ± 10.4	42.5 ± 12.4	NA ± NA ^[1]
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0
Asian	7	3	0	0	10
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	0	0	0	0
White	0	0	10	4	14
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0	0	0	0	0
Not Hispanic or Latino	7	3	10	4	24
Unknown or Not Reported	0	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Number of participants with adverse events (AEs) [ Time Frame: Upto Final Follow-up or Early Termination (Day 84) ]

Measure Type	Primary
Measure Name	Number of participants with adverse events (AEs)
Measure Description	The safety and tolerability of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Upto Final Follow-up or Early Termination (Day 84)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all participants who received at least 1 dose of MEDI7352 or placebo.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Japanese- Placebo	Caucasian- MEDI7352	Caucasian- Placebo
Number of Participants Analyzed [units:participants]	7	3	10	4
Number of participants with adverse events (AEs) [units: Participants]
Any AE	5	2	10	2
Any SAE	0	0	0	0
Any SAE with outcome of death	0	0	0	0
Any AE leading to discontinuation of IMP	0	0	1	0
Any possibly related AE	5	2	7	1
Any possibly related SAE	0	0	0	0

No statistical analysis provided for Number of participants with adverse events (AEs)

2. Secondary Outcome Measure: Area under the serum concentration-time curve from time 0 to infinity (AUCinf) [ Time Frame: Day 1 ]

Measure Type	Secondary
Measure Name	Area under the serum concentration-time curve from time 0 to infinity (AUCinf)
Measure Description	The AUCinf of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data. Here, the number of participants analyzed signifies the participant with available data that were analyzed for the outcome measure.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	5
Area under the serum concentration-time curve from time 0 to infinity (AUCinf) [units: Daynanogram/milliliter (dayng/mL)] Geometric Mean (Geometric Coefficient of Variation)	143200 (25.53%)	150100 (31.50%)

No statistical analysis provided for Area under the serum concentration-time curve from time 0 to infinity (AUCinf)

3. Secondary Outcome Measure: Maximum concentration (Cmax) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Maximum concentration (Cmax)
Measure Description	The Cmax of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set will consist of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Maximum concentration (Cmax) [units: nanogram/milliliter (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)
Day 1	12350 (38.01%)	10980 (61.91%)
Day 43	11610 (55.26%)	9445 (127.0%)

No statistical analysis provided for Maximum concentration (Cmax)

4. Secondary Outcome Measure: Time of Cmax (tmax) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Time of Cmax (tmax)
Measure Description	The tmax of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Time of Cmax (tmax) [units: Day] Median (Full Range)
Day 1	3.00 (3.00 to 7.00)	3.00 (3.00 to 7.00)
Day 43	3.00 (3.00 to 5.00)	3.00 (3.00 to 5.00)

No statistical analysis provided for Time of Cmax (tmax)

5. Secondary Outcome Measure: Area under the serum concentration-time curve from time 0 to the time of the last quantifiable serum concentration (AUClast) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Area under the serum concentration-time curve from time 0 to the time of the last quantifiable serum concentration (AUClast)
Measure Description	The AUClast of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Area under the serum concentration-time curve from time 0 to the time of the last quantifiable serum concentration (AUClast) [units: Daynanogram/milliliter (dayng/mL)] Geometric Mean (Geometric Coefficient of Variation)
Day 1	114000 (24.63%)	87380 (53.06%)
Day 43	78530 (103.8%)	70810 (245.6%)

No statistical analysis provided for Area under the serum concentration-time curve from time 0 to the time of the last quantifiable serum concentration (AUClast)

6. Secondary Outcome Measure: Area under the serum concentration-time curve for the dosing interval (AUCτ) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Area under the serum concentration-time curve for the dosing interval (AUCτ)
Measure Description	The AUCτ of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Area under the serum concentration-time curve for the dosing interval (AUCτ) [units: day*ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Day 1	114000 (24.63%)	86830 (49.72%)
Day 43	76750 (84.80%)	103900 (31.27%)

No statistical analysis provided for Area under the serum concentration-time curve for the dosing interval (AUCτ)

7. Secondary Outcome Measure: Average drug concentration over a dosing interval (Cavg) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Average drug concentration over a dosing interval (Cavg)
Measure Description	The Cavg of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Average drug concentration over a dosing interval (Cavg) [units: nanogram/milliliter (ng/mL)] Geometric Mean (Geometric Coefficient of Variation)
Day 1	8144 (24.63%)	6202 (49.72%)
Day 43	5482 (84.80%)	7422 (31.27%)

No statistical analysis provided for Average drug concentration over a dosing interval (Cavg)

8. Secondary Outcome Measure: Half-life (t½λz) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Half-life (t½λz)
Measure Description	The t½λz of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Half-life (t½λz) [units: Day] Geometric Mean (Geometric Coefficient of Variation)
Day 1	4.996 (25.81%)	4.963 (22.84%)
Day 43	3.139 (40.96%)	3.595 (25.16%)

No statistical analysis provided for Half-life (t½λz)

9. Secondary Outcome Measure: Apparent total body clearance (CL/F) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Apparent total body clearance (CL/F)
Measure Description	The CL/F of MEDI7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Apparent total body clearance (CL/F) [units: Liter/day (L/day)] Geometric Mean (Geometric Coefficient of Variation)
Day 1	1.047 (25.53%)	0.9994 (31.50%)
Day 43	1.954 (84.80%)	1.444 (31.27%)

No statistical analysis provided for Apparent total body clearance (CL/F)

10. Secondary Outcome Measure: Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F) [ Time Frame: Day 1 and Day 43 ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F)
Measure Description	The Vz/F of MEDl7352 in healthy Japanese and Caucasian participants following multiple dosing by the SC route was assessed.
Time Frame	Day 1 and Day 43
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all participants who received at least 1 dose of MEDI7352 for whom any quantifiable post-baseline PK data are available and who have no important protocol deviations thought to impact on the analysis of the PK data.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	7	10
Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F) [units: Liter (L)] Geometric Mean (Geometric Coefficient of Variation)
Day 1	7.549 (25.77%)	6.861 (39.84%)
Day 43	7.576 (33.75%)	7.486 (19.97%)

No statistical analysis provided for Apparent volume of distribution during the terminal phase (extravascular administration) (Vz/F)

11. Secondary Outcome Measure: Number of participants with positive/negative antidrug antibodies (ADA) results for MEDI7352 [ Time Frame: Days 1, 15, 29 and 43 and at Follow-up Visits (Days 50, 64, and 84) ]

Measure Type	Secondary
Measure Name	Number of participants with positive/negative antidrug antibodies (ADA) results for MEDI7352
Measure Description	Number of participants with positive/negative antidrug antibodies (ADA) results for MEDI7352 in healthy Japanese and Caucasian participants with respect to immunogenicity were assessed.
Time Frame	Days 1, 15, 29 and 43 and at Follow-up Visits (Days 50, 64, and 84)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all participants who received at least 1 dose of MEDI7352 or placebo.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Japanese- Placebo	Caucasian- MEDI7352	Caucasian- Placebo
Number of Participants Analyzed [units:participants]	7	3	10	4
Number of participants with positive/negative antidrug antibodies (ADA) results for MEDI7352 [units: Participants]
Day 1: Positive	0	0	0	0
Day 15: Positive	1	0	6	0
Day 29: Positive	1	0	3	0
Day 43: Positive	1	0	3	0
Day 50: Positive	1	0	3	0
Day 64: Positive	2	0	3	0
Day 84: Positive	3	0	2	0
Day 1: Negative	7	3	10	4
Day 15: Negative	6	3	3	4
Day 29: Negative	6	3	4	3
Day 43: Negative	6	3	4	3
Day 50: Negative	6	3	4	3
Day 64: Negative	4	3	4	3
Day 84: Negative	3	3	5	3

No statistical analysis provided for Number of participants with positive/negative antidrug antibodies (ADA) results for MEDI7352

12. Secondary Outcome Measure: ADA titers testing for all ADA-positive samples [ Time Frame: Days 64, and Follow-up visit (Day 84) ]

Measure Type	Secondary
Measure Name	ADA titers testing for all ADA-positive samples
Measure Description	ADA titers testing for all ADA-positive samples for MEDI7352 in healthy Japanese and Caucasian participants with respect to immunogenicity following multiple dosing by the SC route was assessed.
Time Frame	Days 64, and Follow-up visit (Day 84)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set included all participants who received at least 1 dose of MEDI7352 or placebo. Here, the number of participants analyzed signifies the participant with available data that were analyzed for the outcome measure.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Measured Values

	Japanese- MEDI7352	Caucasian- MEDI7352
Number of Participants Analyzed [units:participants]	3	3
ADA titers testing for all ADA-positive samples [units: Unitless] Median (Full Range)
Day 64	NA (60 to 240) ^[1]	480 (240 to 480)
Day 84	240 (60 to 240)	NA (30 to 480) ^[1]

No statistical analysis provided for ADA titers testing for all ADA-positive samples

Serious Adverse Events

Time Frame	Up to Final Follow-up or Early Termination (Day 84)
Additional Description	No text entered.

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Serious Adverse Events

	Japanese- MEDI7352	Japanese- Placebo	Caucasian- MEDI7352	Caucasian- Placebo
Total, serious adverse events
# participants affected / at risk	0/7 (0.00%)	0/3 (0.00%)	0/10 (0.00%)	0/4 (0.00%)

Other Adverse Events

Time Frame	Up to Final Follow-up or Early Termination (Day 84)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Japanese- MEDI7352	Healthy Japanese participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Japanese- Placebo	Healthy Japanese participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- MEDI7352	Healthy Caucasian participants received 1 dose of MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.
Caucasian- Placebo	Healthy Caucasian participants received 1 dose of placebo matched to MEDI7352 every 2 weeks (4 doses in total) on Days 1, 15, 29, and 43 under fasted conditions in the treatment period of 8 weeks.

Other Adverse Events

Japanese- MEDI7352

Japanese- Placebo

Caucasian- MEDI7352

Caucasian- Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

5/7 (71.43%)

2/3 (66.67%)

10/10 (100.00%)

2/4 (50.00%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

0/7 (0.00%)

1/3 (33.33%)

0/10 (0.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹

# participants affected / at risk

0/7 (0.00%)

1/3 (33.33%)

0/10 (0.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Injection site erythema¹

# participants affected / at risk

5/7 (71.43%)

1/3 (33.33%)

6/10 (60.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Injection site swelling¹

# participants affected / at risk

1/7 (14.29%)

1/3 (33.33%)

0/10 (0.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Pyrexia¹

# participants affected / at risk

0/7 (0.00%)

1/3 (33.33%)

0/10 (0.00%)

0/4 (0.00%)

# events

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Immune system disorders

Seasonal allergy¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Nervous system disorders

Anosmia¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

1/4 (25.00%)

# events

Nervous system disorders

Hypoaesthesia¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Nervous system disorders

Memory impairment¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Nervous system disorders

Paraesthesia¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

0/7 (0.00%)

1/3 (33.33%)

3/10 (30.00%)

0/4 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

2/10 (20.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

1/4 (25.00%)

# events

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

2/10 (20.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

2/10 (20.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Musculoskeletal chest pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Musculoskeletal and connective tissue disorders

Rhabdomyolysis¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Catheter site erythema¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Injection site bruising¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Injection site discomfort¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Injection site pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

1/4 (25.00%)

# events

General disorders and administration site conditions

Injection site pruritus¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

General disorders and administration site conditions

Non-cardiac chest pain¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

General disorders and administration site conditions

Vessel puncture site bruise¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Injury, poisoning and procedural complications

Arthropod bite¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

Injury, poisoning and procedural complications

Contusion¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

2/10 (20.00%)

0/4 (0.00%)

# events

Injury, poisoning and procedural complications

Road traffic accident¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

1/10 (10.00%)

0/4 (0.00%)

# events

Injury, poisoning and procedural complications

Sunburn¹

# participants affected / at risk

0/7 (0.00%)

0/3 (0.00%)

0/10 (0.00%)

1/4 (25.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 24.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	AstraZeneca Clinical study Information Center
Organization:	Global Clinical Lead
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

CSR Synopsis

Trial Results Summaries