Chronic Kidney Disease Clinical Trial
— SAPPHIREOfficial title:
A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled Study of Verinurad and Allopurinol in Patients With Chronic KIdney Disease and Hyperuricaemia
Verified date | January 2023 |
Source | AstraZeneca |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 861 |
Est. completion date | November 22, 2021 |
Est. primary completion date | November 22, 2021 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 130 Years |
Eligibility | 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. ยท 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 |
Country | Name | City | State |
---|---|---|---|
Czechia | Research Site | Frydek | |
Czechia | Research Site | Praha 2 | |
Czechia | Research Site | Praha 6 | |
Czechia | Research Site | Slany | |
Czechia | Research Site | Trebíc | |
France | Research Site | Annonay | |
France | Research Site | Grenoble cedex 9 | |
France | Research Site | Marseille cedex 5 | |
France | Research Site | Paris | |
France | Research Site | Paris | |
France | Research Site | Rouen | |
France | Research Site | Tours | |
Hungary | Research Site | Baja | |
Hungary | Research Site | Balatonfured | |
Hungary | Research Site | Budapest | |
Hungary | Research Site | Budapest | |
Hungary | Research Site | Debrecen | |
Hungary | Research Site | Debrecen | |
Hungary | Research Site | Hatvan | |
Hungary | Research Site | Kaposvár | |
Hungary | Research Site | Nyíregyháza | |
Hungary | Research Site | Nyíregyháza | |
Hungary | Research Site | Szeged | |
Hungary | Research Site | Zalaegerszeg | |
Israel | Research Site | Afula | |
Israel | Research Site | Ashdod | |
Israel | Research Site | Ashkelon | |
Israel | Research Site | Beer Sheba | |
Israel | Research Site | Haifa | |
Israel | Research Site | Haifa | |
Israel | Research Site | Haifa | |
Israel | Research Site | Holon | |
Israel | Research Site | Kfar Sava | |
Israel | Research Site | Nahariya | |
Israel | Research Site | Nazareth | |
Israel | Research Site | Petach-Tikva | |
Israel | Research Site | Ramat Gan | |
Israel | Research Site | Rehovot | |
Israel | Research Site | Safed | |
Israel | Research Site | Tel-Aviv | |
Israel | Research Site | Tiberias | |
Italy | Research Site | Genova | |
Italy | Research Site | Milano | |
Italy | Research Site | Parma | |
Italy | Research Site | Pavia | |
Italy | Research Site | Verona | |
Mexico | Research Site | Ciudad Madero | |
Mexico | Research Site | Estado de Mexico | |
Mexico | Research Site | Guadalajara | |
Mexico | Research Site | Mexico | |
Mexico | Research Site | Mexico | |
Mexico | Research Site | Tijuana | |
Mexico | Research Site | Veracruz | |
Poland | Research Site | Krakow | |
Poland | Research Site | Lodz | |
Poland | Research Site | Lublin | |
Poland | Research Site | Poznan | |
Poland | Research Site | Rzeszów | |
Poland | Research Site | Warszawa | |
Poland | Research Site | Wroclaw | |
Romania | Research Site | Bucuresti | |
Romania | Research Site | Bucuresti | |
Romania | Research Site | Bucuresti | |
Romania | Research Site | Bucuresti | |
Romania | Research Site | Deva | |
Romania | Research Site | Ploiesti | |
Romania | Research Site | Satu Mare | |
Romania | Research Site | Timi?oara | |
Slovakia | Research Site | Bardejov | |
Slovakia | Research Site | Bratislava | |
Slovakia | Research Site | Hlohovec | |
Slovakia | Research Site | Kosice | |
Slovakia | Research Site | Kralovsky Chlmec | |
Slovakia | Research Site | Lucenec | |
Slovakia | Research Site | Puchov | |
Slovakia | Research Site | Rimavska Sobota | |
Slovakia | Research Site | Svidnik | |
South Africa | Research Site | Benoni | |
South Africa | Research Site | Cape Town | |
South Africa | Research Site | Cape Town | |
South Africa | Research Site | Cape Town | |
South Africa | Research Site | Cape Town | |
South Africa | Research Site | Durban | |
South Africa | Research Site | Durban | |
South Africa | Research Site | George | |
South Africa | Research Site | Johannesburg | |
South Africa | Research Site | Johannesburg | |
South Africa | Research Site | Krugersdorp | |
South Africa | Research Site | Lenasia | |
South Africa | Research Site | Paarl | |
South Africa | Research Site | Stanger | |
South Africa | Research Site | Tshwane | |
South Africa | Research Site | Worcester | |
Spain | Research Site | Alicante | |
Spain | Research Site | Alicante | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Ciudad Real | |
Spain | Research Site | Cordoba | |
Spain | Research Site | Girona | |
Spain | Research Site | Granada | |
Spain | Research Site | L'Hospitalet De Llobregat | |
Spain | Research Site | Málaga | |
Spain | Research Site | Palma de Mallorca | |
Spain | Research Site | Puerto De Sagunto | |
Spain | Research Site | Santander | |
Spain | Research Site | Sevilla | |
Spain | Research Site | Valencia | |
Spain | Research Site | Valencia | |
United States | Research Site | Alexandria | Virginia |
United States | Research Site | Altamonte Springs | Florida |
United States | Research Site | Arlington | Texas |
United States | Research Site | Asheville | North Carolina |
United States | Research Site | Asheville | North Carolina |
United States | Research Site | Bakersfield | California |
United States | Research Site | Bloomfield | Connecticut |
United States | Research Site | Bronx | New York |
United States | Research Site | Canyon Country | California |
United States | Research Site | Denver | Colorado |
United States | Research Site | El Paso | Texas |
United States | Research Site | Flint | Michigan |
United States | Research Site | Flint | Michigan |
United States | Research Site | Hialeah | Florida |
United States | Research Site | Houston | Texas |
United States | Research Site | Huntsville | Alabama |
United States | Research Site | Jacksonville | Florida |
United States | Research Site | Jamaica | New York |
United States | Research Site | Knoxville | Tennessee |
United States | Research Site | Laguna Hills | California |
United States | Research Site | Lampasas | Texas |
United States | Research Site | Lauderdale Lakes | Florida |
United States | Research Site | Lawrenceville | Georgia |
United States | Research Site | Lewisville | Texas |
United States | Research Site | Long Beach | California |
United States | Research Site | Miami | Florida |
United States | Research Site | Miami | Florida |
United States | Research Site | Miami | Florida |
United States | Research Site | Miami Lakes | Florida |
United States | Research Site | Milwaukee | Wisconsin |
United States | Research Site | Minneapolis | Minnesota |
United States | Research Site | Northridge | California |
United States | Research Site | Ocala | Florida |
United States | Research Site | Ocoee | Florida |
United States | Research Site | Orange | California |
United States | Research Site | Orangeburg | South Carolina |
United States | Research Site | Paducah | Kentucky |
United States | Research Site | Pearland | Texas |
United States | Research Site | Pembroke Pines | Florida |
United States | Research Site | Philadelphia | Pennsylvania |
United States | Research Site | Port Charlotte | Florida |
United States | Research Site | Rocky Mount | North Carolina |
United States | Research Site | Saint Clair Shores | Michigan |
United States | Research Site | San Antonio | Texas |
United States | Research Site | San Antonio | Texas |
United States | Research Site | San Antonio | Texas |
United States | Research Site | Takoma Park | Maryland |
United States | Research Site | Thousand Oaks | California |
United States | Research Site | Vacaville | California |
United States | Research Site | Victorville | California |
United States | Research Site | Washington | District of Columbia |
United States | Research Site | Wauconda | Illinois |
United States | Research Site | Wilmington | North Carolina |
United States | Research Site | Winston-Salem | North Carolina |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
United States, Czechia, France, Hungary, Israel, Italy, Mexico, Poland, Romania, Slovakia, South Africa, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Urinary Albumin to Creatinine Ratio (uACR) (mg/g) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM) | Change from baseline in uACR at 12 months (Visit 10) for comparison of Switch dose protocol version 5.0 (PA5) versus double-capsule Placebo.
The statistical model applied was an MMRM, which was basically the same as the one applied in the primary analysis but adjusted for a 12 month horizon and adapted to the double-capsule regimen from Visit 9 on. |
Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10) | |
Secondary | Serum Uric Acid (sUA) (mg/dL) Change From Baseline at 6 Months (Visit 8), Repeated Measures Mixed Model (MMRM) | Change from baseline in sUA at 6 months (Visit 8), there were 7 comparisons requested for each endpoint, namely:
High dose vs Placebo Inter. dose vs Placebo Low dose vs Placebo High dose vs Allopurinol Inter. dose vs Allopurinol Low dose vs Allopurinol Allopurinol vs Placebo. |
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8) | |
Secondary | Serum Uric Acid (sUA) Change From Baseline at 12 Months (Visit 10), Repeated Measures Mixed Model (MMRM) | Change from baseline in sUA at 12 months (Visit 10) for comparison of Switch dose protocol version 5.0 (PA5) versus double-capsule Placebo. | Baseline to 12 months (Visit 10); analysis at 12 months (Visit 10) | |
Secondary | Estimated Glomerular Filtration Rate (eGFR) (mL/Min/1.73 m²) Change From Baseline at 6 Months (V8), Repeated Measures Mixed Model (MMRM) | Change from baseline in eGFR at 6 months (Visit 8), there were 7 comparisons requested for this endpoint, namely:
High dose vs Placebo Inter. dose vs Placebo Low dose vs Placebo High dose vs Allopurinol Inter. dose vs Allopurinol Low dose vs Allopurinol Allopurinol vs Placebo. |
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8) | |
Secondary | Estimated Glomerular Filtration Rate (eGFR) (mL/Min/1.73 m²) Change From Baseline at 12 Months (Visit 10) | Change from baseline in eGFR at 12 months (Visit 10) for the following treatments:
High Dose Inter. Dose Low Dose (a) Switch Dose protocol version 5.0 (PA5) (b) Allopurinol Placebo Subjects that switched from Verinurad 3 mg to Verinurad 24 mg at Visit 9 are not included in this group for Visit 10. Contains all subjects randomized to the low dose group that later switched to Verinurad 24 mg plus Allopurinol 300 mg. |
Change from baseline to 12 months (Visit 10) | |
Secondary | S-creatinine (mg/dL) Change From Baseline at 6 Months (V8), Repeated Measures Mixed Model (MMRM) | Change from baseline in S-creatinine at 6 months (Visit 8), there were 7 comparisons requested for this endpoint, namely:
High dose vs Placebo Inter. dose vs Placebo Low dose vs Placebo High dose vs Allopurinol Inter. dose vs Allopurinol Low dose vs Allopurinol Allopurinol vs Placebo. |
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8) | |
Secondary | S-creatinine (mg/dL) Change From Baseline at 12 Months (Visit 10) | Change from baseline in S-creatinine at 12 months (Visit 10) for the following treatments:
High Dose Inter. Dose Low Dose (a) Switch Dose protocol version 5.0 (PA5) (b) Allopurinol Placebo Subjects that switched from Verinurad 3 mg to Verinurad 24 mg at Visit 9 are not included in this group for Visit 10. Contains all subjects randomized to the low dose group that later switched to Verinurad 24 mg plus Allopurinol 300 mg. |
Change from baseline to 12 months (Visit 10) | |
Secondary | P-cystatin C (mg/L) Change From Baseline at 6 Months (V8), Repeated Measures Mixed Model (MMRM) | Change from baseline in P-cystatin C at 6 months (Visit 8), there were 7 comparisons requested for this endpoint, namely:
High dose vs Placebo Inter. dose vs Placebo Low dose vs Placebo High dose vs Allopurinol Inter. dose vs Allopurinol Low dose vs Allopurinol Allopurinol vs Placebo. |
Baseline to 9 months (Visit 9); analysis at 6 months (Visit 8) | |
Secondary | P-cystatin C (mg/L) Change From Baseline at 12 Months (Visit 10) | Change from baseline in S-creatinine at 12 months (Visit 10) for the following treatments:
High Dose Inter. Dose Low Dose (a) Switch Dose protocol version 5.0 (PA5) (b) Allopurinol Placebo Subjects that switched from Verinurad 3 mg to Verinurad 24 mg at Visit 9 are not included in this group for Visit 10. Contains all subjects randomized to the low dose group that later switched to Verinurad 24 mg plus Allopurinol 300 mg. |
Change from baseline to 12 months (Visit 10) |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05491642 -
A Study in Male and Female Participants (After Menopause) With Mild to Moderate High Blood Pressure to Learn How Safe the Study Treatment BAY3283142 is, How it Affects the Body and How it Moves Into, Through and Out of the Body After Taking Single and Multiple Doses
|
Phase 1 | |
Recruiting |
NCT06363097 -
Urinary Uromodulin, Dietary Sodium Intake and Ambulatory Blood Pressure in Patients With Chronic Kidney Disease
|
||
Terminated |
NCT04043026 -
The Effects of Renal Function and Atrial Fibrillation on Lipoproteins and Clot Structure/Function
|
||
Completed |
NCT05318014 -
Low-protein Formula Supplements in Chronic Kidney Disease
|
N/A | |
Active, not recruiting |
NCT06071065 -
Clinical Pharmacist Intervention on Medication Adherence and Clinical Outcomes in Chronic Kidney Disease Patients
|
N/A | |
Completed |
NCT02878317 -
Skin Autofluorescence as a Risk Marker in People Receiving Dialysis.
|
||
Not yet recruiting |
NCT06039254 -
Safety and Pharmacokinetics of HRS-1780 in Healthy Subjects and Subjects With Impaired Renal Function
|
Phase 1 | |
Recruiting |
NCT03160326 -
The QUALITY Vets Project: Muscle Quality and Kidney Disease
|
||
Completed |
NCT02836574 -
A Study of Renal Autologous Cell Therapy (REACT) in Type 2 Diabetics With Chronic Kidney Disease
|
Phase 2 | |
Completed |
NCT02875886 -
DD-study: Diet or Diuretics for Salt-sensitivity in Chronic Kidney Disease
|
Phase 4 | |
Withdrawn |
NCT02885545 -
The Strategy to Prevent Hemorrhage Associated With Anticoagulation in Renal Disease Management (STOP HARM) Trial
|
Phase 4 | |
Completed |
NCT02896309 -
The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity
|
N/A | |
Completed |
NCT02888171 -
Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With CKD and Iron Deficiency
|
N/A | |
Completed |
NCT02756520 -
Observational Study on CKD Treatment With a Ketosteril Supplemented Protein-restricted Diet (Keto-024-CNI)
|
||
Active, not recruiting |
NCT02483039 -
Nephrologist Follow-up Versus Usual Care After an Acute Kidney Injury Hospitalization
|
N/A | |
Completed |
NCT02369549 -
Micro-Particle Curcumin for the Treatment of Chronic Kidney Disease
|
Phase 3 | |
Completed |
NCT02992548 -
Effect of Pravastatin on Erythrocyte Membrane Fatty Acid Contents in Patients With Chronic Kidney Disease
|
Phase 4 | |
Terminated |
NCT02543177 -
Optimised Procedure in Patients With NSTEMI and CKD
|
N/A | |
Recruiting |
NCT02205944 -
Impact of Presurgical Exercise on Hemodialysis Fistula Outcomes
|
N/A | |
Active, not recruiting |
NCT02231138 -
Efficacy and Safety of Abelmoschus Manihot for Chronic Kidney Disease
|
Phase 4 |