Anifrolumab PK study for Systemic Lupus Erythematosus (SLE)

Study identifier:D3468C00002

ClinicalTrials.gov identifier:NCT05001698

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, Open-label, Single-Arm, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Anifrolumab in Chinese Participants with Systemic Lupus Erythematosus (SLE)

Medical condition

Systemic Lupus Erythematosus

Phase

Phase 1

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 60 Years

Date

Study Start Date: 27 Jul 2021

Primary Completion Date: 02 Jun 2022

Study Completion Date: 02 Jun 2022

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 May 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1. Aged 18 to 60 years.
2. Body weight ≥ 40 kg.
3. Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.
4. Must be receiving at least one of the following SOC regimens at screening:
(a) oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;
(b) Immunosuppressant(s) with or without OCS: antimalarials, AZA, MMF, MTX, mizoribine permitted; stable for ≥ 8 weeks; maximum dose required;
(c) Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.
5. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
6. At screening, SLEDAI-2K score ≥ 6 points.
7. Chest imaging shows no clinically significant abnormalities (unless due to SLE).
8. No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.
9. All participants should use effective contraception methods as protocol requests.

Exclusion Criteria

1. History or current diagnose of clinically significant non-SLE related vasculitis, severe or unstable neuropsychiatric SLE, active severe SLE-driven renal disease, catastrophic anti-phospholipid syndrome, inflammatory joint or skin disease other than SLE, non-SLE disease that has required treatment of certain dosage of corticosteroid.
2. History or evidence of suicidal ideation or suicidal behavior.
3. History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE.
4. History of recurrent infection requiring hospitalization and IV antibiotics, or opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.
5. History of immunodeficient condition, HIV positive included.
6. Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable.
7. History of severe case of herpes zoster.
8. Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening.
9. Acute COVID-19 infection or history of severe COVID-19.
10. History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ.
11. Women participants with abnormal pap smear results.
12. Prior receipt of anifrolumab ,or any commercially available biologic agent, or protein kinase inhibitor or any investigational product within 5 half-lives, including B cell-depleting therapy, belimumab, JAK or BTK inhibitor.
13. Known history of allergy to any component of the IP formulation or protein related products.
14. Receipt of any of the following:
(a) Intramuscular or IV glucocorticosteroids within 6 weeks;
(b) Any live or attenuated vaccine within 8 weeks;
(c) Any restricted medication listed in protocol;
(d) Blood transfusion within 4 weeks.
15. Certain laboratory test results requirements.
16. Concurrent enrolment in another clinical study.
17. History or current alcohol, drug or chemical abuse within 1 year.
18. Major surgery within 8 weeks or planned elective major surgery.
19. Blood donation or blood loss more than 400 mL within 3 months.

Location

Research Site

Shanghai, China, 200040

Location

Research Site

Nantong, China, 226001

Location

Research Site

Shanghai, China, 200025

Arms	Assigned Interventions
Experimental: Anifrolumab All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Participant Flow: Overall Study

	Anifrolumab
STARTED	15
COMPLETED	12
NOT COMPLETED	3
Unable to Complete important visit due to COVID-19 situation.	2
Subject Decision	1

Baseline Characteristics

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

Safety Set

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Baseline Measures

	Anifrolumab
Number of Participants [units: Participants]	15
Age Continuous [units: Years] Mean ± Standard Deviation	38.5 ± 9.4
Sex: Female, Male [units: ]
Female	14
Male	1
Race/Ethnicity, Customized [units: Participants]
Hispanic or Latino	0
Not Hispanic or Latino	15

Outcome Measures

1. Primary Outcome Measure: Tmax Dose 1 [ Time Frame: Day 1 to Day 29 ]

Measure Type	Primary
Measure Name	Tmax Dose 1
Measure Description	Time to reach peak or maximum observed concentration (Tmax) following the first dose of anifrolumab
Time Frame	Day 1 to Day 29
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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	15
Tmax Dose 1 [units: day] Median (Full Range)	0.05 (0.03 to 0.06)

No statistical analysis provided for Tmax Dose 1

2. Primary Outcome Measure: Cmax Dose 1 [ Time Frame: Day 1 to Day 29 ]

Measure Type	Primary
Measure Name	Cmax Dose 1
Measure Description	Maximum observed serum (peak) concentration (Cmax) of the first dose of anifrolumab
Time Frame	Day 1 to Day 29
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	15
Cmax Dose 1 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	111.5 (16.51%)

No statistical analysis provided for Cmax Dose 1

3. Primary Outcome Measure: AUC[tau] Dose 1 [ Time Frame: Day 1 to Day 29 ]

Measure Type	Primary
Measure Name	AUC[tau] Dose 1
Measure Description	Area under the serum concentration-time curve within the dosing interval (AUC[tau]) of anifrolumab
Time Frame	Day 1 to Day 29
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	15
AUC[tau] Dose 1 [units: day*ug/ml] Geometric Mean (Geometric Coefficient of Variation)	1043 (35.37%)

No statistical analysis provided for AUC[tau] Dose 1

4. Primary Outcome Measure: Ctrough Dose 1 [ Time Frame: Day 29 ]

Measure Type	Primary
Measure Name	Ctrough Dose 1
Measure Description	Pre-dose trough observed serum concentration (Ctrough) of anifrolumab of the first dose (pre-dose concentration at Day 29)
Time Frame	Day 29
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	12
Ctrough Dose 1 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	8.671 (180.3%)

No statistical analysis provided for Ctrough Dose 1

5. Primary Outcome Measure: CL Dose 1 [ Time Frame: Day 1 to Day 29 ]

Measure Type	Primary
Measure Name	CL Dose 1
Measure Description	Total body clearance (CL) of drug from serum after the first intravascular administration of anifrolumab
Time Frame	Day 1 to Day 29
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	6
CL Dose 1 [units: mL/day] Geometric Mean (Geometric Coefficient of Variation)	362.6 (43.40%)

No statistical analysis provided for CL Dose 1

6. Primary Outcome Measure: Tmax Dose 3 [ Time Frame: Day 57 to Day 85 ]

Measure Type	Primary
Measure Name	Tmax Dose 3
Measure Description	Time to reach peak or maximum observed concentration (Tmax) following the third dose of anifrolumab
Time Frame	Day 57 to Day 85
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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	11
Tmax Dose 3 [units: day] Median (Full Range)	0.04 (0.04 to 0.05)

No statistical analysis provided for Tmax Dose 3

7. Primary Outcome Measure: Cmax Dose 3 [ Time Frame: Day 57 to Day 85 ]

Measure Type	Primary
Measure Name	Cmax Dose 3
Measure Description	Maximum observed serum (peak) concentration (Cmax) of the third dose of anifrolumab
Time Frame	Day 57 to Day 85
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	11
Cmax Dose 3 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	122.8 (36.16%)

No statistical analysis provided for Cmax Dose 3

8. Primary Outcome Measure: AUC[tau] Dose 3 [ Time Frame: Day 57 to Day 85 ]

Measure Type	Primary
Measure Name	AUC[tau] Dose 3
Measure Description	Area under the serum concentration-time curve within the dosing interval (AUC[tau]) of anifrolumab
Time Frame	Day 57 to Day 85
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	11
AUC[tau] Dose 3 [units: day*ug/ml] Geometric Mean (Geometric Coefficient of Variation)	1315 (54.55%)

No statistical analysis provided for AUC[tau] Dose 3

9. Primary Outcome Measure: Ctrough Dose 3 [ Time Frame: Day 85 ]

Measure Type	Primary
Measure Name	Ctrough Dose 3
Measure Description	Trough observed serum concentration (Ctrough) of anifrolumab of the third dose (concentration at Day 85)
Time Frame	Day 85
Safety Issue?

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 pharmacokinetic (PK) analysis population includes all participants who received anifrolumab with no important protocol deviations thought to impact the PK profile, and who have at least one measurable post-dose anifrolumab concentration. Participants who have intermittent missing PK sampling are evaluated case-by-case for inclusion in the PK analysis set.

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	10
Ctrough Dose 3 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	17.39 (127.6%)

No statistical analysis provided for Ctrough Dose 3

10. Secondary Outcome Measure: Anti-drug antibodies (ADA). Number of ADA positive over time. [ Time Frame: Day 1, 85, 113, 141 ]

Measure Type	Secondary
Measure Name	Anti-drug antibodies (ADA). Number of ADA positive over time.
Measure Description	To characterise the immunogenicity of anifrolumab via IV infusion.
Time Frame	Day 1, 85, 113, 141
Safety Issue?

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.
Safety Set

Reporting Groups

	Description
Anifrolumab	All eligible participants will receive anifrolumab via intravenous (IV) infusion pump.

Measured Values

	Anifrolumab
Number of Participants Analyzed [units:participants]	15
Anti-drug antibodies (ADA). Number of ADA positive over time. [units: Participants]
Baseline	0
Day 85	0
8 weeks post last dose	0
12 weeks post last dose	0

No statistical analysis provided for Anti-drug antibodies (ADA). Number of ADA positive over time.

Serious Adverse Events

Time Frame	From first administration of study treatment until 84 days after the last dose of study medication.
Additional Description	No text entered.

Reporting Groups

	Description
Anifrolumab 300mg	Description (Arm-group)

Serious Adverse Events

	Anifrolumab 300mg
Total, serious adverse events
# participants affected / at risk	0/15 (0.00%)

Other Adverse Events

Time Frame	From first administration of study treatment until 84 days after the last dose of study medication.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Anifrolumab 300mg	Description (Arm-group)