A Study of Verinurad and Allopurinol in Patients with Chronic Kidney Disease and Hyperuricaemia - SAPPHIRE

Study identifier:D5495C00002

ClinicalTrials.gov identifier:NCT03990363

EudraCT identifier:2018-004079-11

CTIS identifier:N/A

Study Complete

Official Title

A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled Study of Verinurad and Allopurinol in Patients with Chronic KIdney Disease and Hyperuricaemia

Medical condition

Chronic Kidney Disease

Phase

Phase 2

Healthy volunteers

Study drug

Verinurad, Allopurinol, Placebo for Verinurad, Placebo for Allopurinol

Sex

All

Actual Enrollment

861

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 23 Jul 2019

Primary Completion Date: 22 Nov 2021

Study Completion Date: 22 Nov 2021

Study design

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

Verification:

Verified 01 Sept 2023 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

∙ The subject has given written informed consent prior to any mandatory study specific procedures, sampling, and analyses, and is able to understand and comply with all study procedures
∙ Adult Patient ≥18 years of age with CKD for >3 months.
∙ Patients with background standard of care treatment for albuminuria and/or T2DM and treated according to locally recognised guidelines. Therapy optimised and stable for ≥4 weeks before study entry and including an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, unless justified.
∙ If treated with a sodium-glucose transport protein (SGLT2) inhibitor, stable dose for ≥4 weeks before randomisation.
∙ Meeting screening criteria for sUA and eGFR (Visit 2): sUA ≥6.0 mg/dL. ∙ eGFR ≥25 mL/min/1.73 m2 Chronic Kidney Disease Epidemiology Collaboration
∙ UACR between 30 mg/g and 5000 mg/g.
∙ Female patients: Negative pregnancy test for childbearing potential. 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception during the study and 4 weeks after the last dose of study treatment.

Exclusion Criteria

• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody associated vasculitis (granulomatosis with
polyangiitis [Wegener's granulomatosis], microscopic polyangiitis, or eosinophilic
granulomatosis with polyangiitis [Churg-Strauss syndrome]).
• History of renal transplantation
• Known carrier of the Human Leukocyte Antigen-B *58:01 allele.
• Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan syndrome
• Patients who in the opinion of investigator are unable to perform the patients’ tasks associated with the protocol or Presence of any condition which, places the patient at undue risk or potentially jeopardises the quality of the data to be generated
• History of stroke, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft in the past 6 months
• Uncontrolled hypertension presenting with systolic blood pressure >180 mm Hg and/or diastolic blood pressure >100 mm Hg
• Diagnosed with heart failure and New York Heart Association Functional Classification Class IV at the time of randomisation
• QT interval corrected by the Fridericia formula >470 msec; patients diagnosed with long QT syndrome; patients with a family history of long QT syndrome.
• Subjects with severe hepatic impairment, as judged by the investigator, of Child-Pugh
Class C (decompensated cirrhosis), or with major cirrhosis complications (eg, hepatorenal
syndrome)
• Receiving cytotoxic or immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• Treated with any drug for hyperuricaemia in the 6 months preceding randomisation.
• Dose of ACEi, ARBs, fenofibrate, guaifenesin, or SGLT2 inhibitors changed within 4 weeks of randomisation or further dose titration expected after randomization

No locations available

Arms	Assigned Interventions
Experimental: High Dose High Dose (mg) (verinurad/allopurinol) Step 1 - titration_ 3/100 Step 2 - titration_ 7.5/200 Step 3 - target dose_ 12/300	Drug: Verinurad Study treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at visit 9 Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Experimental: Intermediate Dose Intermediate Dose (mg) verinurad/allopurinol Step 1 - titration_ 3/100 Step 2 - titration_ 7.5/200 Step 3 - target dose_ 7.5/300	Drug: Verinurad Study treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at visit 9 Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Experimental: Low Dose Low Dose (mg) verinurad/allopurinol Step 1 - titration_3/100 Step 2 - titration_3/200 Step 3 - target dose_3/300. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at Visit 9.	Drug: Verinurad Study treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad. As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at visit 9 Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Experimental: Allopurinol alone (0/300 mg) Step 1 - titration_0/100 Step 2 - titration_0/200 Step 3 - target dose_0/300	Drug: Allopurinol Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Placebo Comparator: Placebo (0/0 mg) Placebo (mg) in 3 steps_0/0	Drug: Placebo for Verinurad Matching Capsule Other Name: Placebo Drug: Placebo for Allopurinol Matching tablet Other Name: Placebo

Documents available

CSR
Download
protocol_redacted
Download
SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]