A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia
SAPPHIRE
A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled Study of Verinurad and Allopurinol in Patients With Chronic KIdney Disease and Hyperuricaemia
1 other identifier
interventional
861
12 countries
165
Brief Summary
The purpose of this clinical research study is to establish the dose of verinurad combined with allopurinol 300 mg once daily that will elicit the desired response; ie, reduction in urinary albumin to creatinine ratio (UACR) at 6 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2019
165 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 30, 2019
CompletedFirst Posted
Study publicly available on registry
June 19, 2019
CompletedStudy Start
First participant enrolled
July 23, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 22, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 22, 2021
CompletedResults Posted
Study results publicly available
March 2, 2023
CompletedMarch 2, 2023
January 1, 2023
2.3 years
May 30, 2019
October 28, 2022
February 1, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Urinary Albumin to Creatinine Ratio (uACR) (mg/g) Change From Baseline at 6 Months (Visit 8), Repeated Measures Mixed Model (MMRM)
Analyses of change from baseline in uACR at 6 months (Visit 8) focused on: * High dose vs Placebo * High dose and Inter. dose combined vs Allopurinol alone * Inter. dose vs Placebo * Low dose vs Placebo * High dose vs Allopurinol * Inter. dose vs Allopurinol * Low dose vs Allopurinol * Allopurinol vs Placebo For High dose and Inter. dose combined the 2 categories merged forming 1 new temporary category.
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8)
Secondary Outcomes (9)
Urinary Albumin to Creatinine Ratio (uACR) (mg/g) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM)
Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10)
Serum Uric Acid (sUA) (mg/dL) Change From Baseline at 6 Months (Visit 8), Repeated Measures Mixed Model (MMRM)
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8)
Serum Uric Acid (sUA) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM)
Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10)
Estimated Glomerular Filtration Rate (eGFR) (mL/Min/1.73 m²) Change From Baseline at 6 Months (V8), Repeated Measures Mixed Model (MMRM)
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8)
Estimated Glomerular Filtration Rate (eGFR) (mL/Min/1.73 m²) Change From Baseline at 12 Months (Visit 10)
Change from baseline to 12 months (Visit 10)
- +4 more secondary outcomes
Study Arms (5)
High Dose
EXPERIMENTALHigh Dose (mg) (verinurad/allopurinol) Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 12/300
Intermediate Dose
EXPERIMENTALIntermediate Dose (mg) verinurad/allopurinol Step 1 - titration\_ 3/100 Step 2 - titration\_ 7.5/200 Step 3 - target dose\_ 7.5/300
Low Dose
EXPERIMENTALLow 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.
Allopurinol alone (0/300 mg)
EXPERIMENTALStep 1 - titration\_0/100 Step 2 - titration\_0/200 Step 3 - target dose\_0/300
Placebo (0/0 mg)
PLACEBO COMPARATORPlacebo (mg) in 3 steps\_0/0
Interventions
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
Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (165)
Research Site
Huntsville, Alabama, 35805, United States
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Bakersfield, California, 93309, United States
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Canyon Country, California, 91351, United States
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Laguna Hills, California, 92653, United States
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Long Beach, California, 90807, United States
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Northridge, California, 91324, United States
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Orange, California, 92868, United States
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Thousand Oaks, California, 91360, United States
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Vacaville, California, 95687, United States
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Victorville, California, 92395, United States
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Denver, Colorado, 80230, United States
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Bloomfield, Connecticut, 06002, United States
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Washington D.C., District of Columbia, 20037, United States
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Altamonte Springs, Florida, 32701, United States
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Hialeah, Florida, 33012, United States
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Jacksonville, Florida, 32204, United States
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Lauderdale Lakes, Florida, 33313, United States
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Miami, Florida, 33015, United States
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Miami, Florida, 33126-2956, United States
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Miami, Florida, 33165, United States
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Miami Lakes, Florida, 33014, United States
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Ocala, Florida, 34471, United States
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Ocoee, Florida, 34761, United States
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Pembroke Pines, Florida, 33026, United States
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Port Charlotte, Florida, 33952, United States
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Lawrenceville, Georgia, 30046, United States
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Wauconda, Illinois, 60084, United States
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Paducah, Kentucky, 42003, United States
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Takoma Park, Maryland, 20912, United States
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Flint, Michigan, 48504, United States
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Flint, Michigan, 48532, United States
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Saint Clair Shores, Michigan, 48081, United States
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Minneapolis, Minnesota, 55404, United States
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Jamaica, New York, 11432, United States
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The Bronx, New York, 10461, United States
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Asheville, North Carolina, 28801, United States
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Asheville, North Carolina, 28803, United States
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Rocky Mount, North Carolina, 27804, United States
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Wilmington, North Carolina, 28401, United States
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Winston-Salem, North Carolina, 27103, United States
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Philadelphia, Pennsylvania, 19107, United States
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Orangeburg, South Carolina, 29118, United States
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Knoxville, Tennessee, 37923, United States
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Arlington, Texas, 76015, United States
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El Paso, Texas, 79935, United States
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Houston, Texas, 77004, United States
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Lampasas, Texas, 76550, United States
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Lewisville, Texas, 75057, United States
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Pearland, Texas, 77584, United States
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San Antonio, Texas, 78212, United States
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San Antonio, Texas, 78231, United States
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San Antonio, Texas, 78258, United States
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Alexandria, Virginia, 22304, United States
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Milwaukee, Wisconsin, 53226, United States
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Frýdek-Místek, 738 01, Czechia
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Prague, 128 08, Czechia
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Prague, 160 00, Czechia
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Slaný, 274 01, Czechia
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Třebíč, 674 01, Czechia
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Annonay, 07103, France
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Grenoble, 38043, France
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Marseille, 13385, France
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Paris, 75018, France
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Paris, 75970, France
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Rouen, 76031, France
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Tours, 37000, France
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Baja, 6500, Hungary
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Balatonfüred, 8230, Hungary
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Budapest, 1033, Hungary
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Budapest, 1036, Hungary
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Debrecen, 4025, Hungary
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Debrecen, 4032, Hungary
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Hatvan, 3000, Hungary
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Kaposvár, 7400, Hungary
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Nyíregyháza, 4400, Hungary
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Nyíregyháza, 4405, Hungary
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Szeged, 6725, Hungary
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Zalaegerszeg, 8900, Hungary
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Afula, 1834111, Israel
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Ashdod, 77000, Israel
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Ashkelon, 78278, Israel
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Beersheba, 8410101, Israel
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Haifa, 3109601, Israel
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Haifa, 34362, Israel
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Haifa, 35152, Israel
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Holon, 58100, Israel
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Kfar Saba, 44281, Israel
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Nahariya, 22100, Israel
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Nazareth, 16100, Israel
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Petah Tikva, 49100, Israel
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Ramat Gan, 52621, Israel
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Rehovot, 7642001, Israel
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Safed, 13100, Israel
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Tel Aviv, 61480, Israel
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Tiberias, 15208, Israel
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Genova, 16132, Italy
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Milan, 20132, Italy
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Parma, 43126, Italy
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Pavia, 27100, Italy
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Verona, 37124, Italy
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Ciudad Madero, 89440, Mexico
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Estado de México, 54800, Mexico
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Guadalajara, 44650, Mexico
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México, 03100, Mexico
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México, 06700, Mexico
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Tijuana, 22500, Mexico
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Veracruz, 91910, Mexico
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Krakow, 31-559, Poland
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Lodz, 90-302, Poland
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Lublin, 20-538, Poland
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Poznan, 61-655, Poland
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Rzeszów, 35-055, Poland
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Warsaw, 00-465, Poland
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Wroclaw, 50-127, Poland
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Bucharest, 010192, Romania
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Bucharest, 010825, Romania
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Bucharest, 050538, Romania
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Bucharest, 40172, Romania
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Deva, 330084, Romania
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Ploieşti, 100342, Romania
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Satu Mare, 440055, Romania
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Timișoara, 300456, Romania
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Bardejov, 085 01, Slovakia
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Bratislava, 85101, Slovakia
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Hlohovec, 920 01, Slovakia
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Košice, Slovakia
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Kráľovský Chlmec, 077 01, Slovakia
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Lučenec, 984 01, Slovakia
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Púchov, 2001, Slovakia
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Rimavská Sobota, 979 01, Slovakia
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Svidník, 08901, Slovakia
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Benoni, 1501, South Africa
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Cape Town, 1730, South Africa
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Cape Town, 7505, South Africa
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Cape Town, 7570, South Africa
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Cape Town, 7925, South Africa
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Durban, 4001, South Africa
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Durban, 4092, South Africa
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George, 6530, South Africa
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Johannesburg, 2001, South Africa
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Johannesburg, 2132, South Africa
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Krugersdorp, 1739, South Africa
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KwaDukuza, 4450, South Africa
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Lenasia, 1827, South Africa
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Paarl, 7647, South Africa
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Pretoria, 0084, South Africa
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Worcester, 6850, South Africa
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Alicante, 03010, Spain
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Alicante, 03550, Spain
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Barcelona, 08003, Spain
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Barcelona, 08023, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Ciudad Real, 13005, Spain
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Córdoba, 14004, Spain
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Girona, 17007, Spain
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Granada, 18012, Spain
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L'Hospitalet de Llobregat, 08907, Spain
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Málaga, 29011, Spain
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Palma de Mallorca, 7120, Spain
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Port de Sagunt, 46520, Spain
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Santander, 39010, Spain
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Seville, 41071, Spain
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Valencia, 46014, Spain
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Valencia, 46017, Spain
Related Publications (2)
Heerspink HJL, Stack AG, Terkeltaub R, Jongs N, Inker LA, Bjursell M, Maklad N, Perl S, Eklund O, Rikte T, Sjostrom CD, Perkovic V; SAPPHIRE Investigators. Combination Treatment with Verinurad and Allopurinol in CKD: A Randomized Placebo and Active Controlled Trial. J Am Soc Nephrol. 2024 May 1;35(5):594-606. doi: 10.1681/ASN.0000000000000326. Epub 2024 Feb 20.
PMID: 38564654DERIVEDHeerspink HJL, Stack AG, Terkeltaub R, Greene TA, Inker LA, Bjursell M, Perl S, Rikte T, Erlandsson F, Perkovic V. Rationale, design, demographics and baseline characteristics of the randomized, controlled, Phase 2b SAPPHIRE study of verinurad plus allopurinol in patients with chronic kidney disease and hyperuricaemia. Nephrol Dial Transplant. 2022 Jul 26;37(8):1461-1471. doi: 10.1093/ndt/gfab237.
PMID: 34383954DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was initially planned to be 108 weeks. However, following the implementation of the amendment in Protocol Version 5.0, all patients discontinued therapy after 60 weeks (Visit 10). Subjects that were on Low dose at Visit 9 were switched to 24 mg dose. The study was terminated in Mexico in March 2021.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 30, 2019
First Posted
June 19, 2019
Study Start
July 23, 2019
Primary Completion
November 22, 2021
Study Completion
November 22, 2021
Last Updated
March 2, 2023
Results First Posted
March 2, 2023
Record last verified: 2023-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.