A Phase IIb trial to find out the effectiveness and safety of verinurad and allopurinol in patients with chronic kidney disease and elevated serum uric acid.
- Conditions
- Chronic kidney disease and hyperuricaemiaMedDRA version: 20.0Level: HLTClassification code 10018067Term: General nutritional disorders NECSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004079-11-IT
- Lead Sponsor
- ASTRAZENECA AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 861
- Provision of signed and dated, written ICF.
- Provision of signed and dated written genetic informed consent prior to collection of sample for genetic analysis
- Patient must be =18 years of age at the time of signing the ICF.
- CKD as defined in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines; ie, there must be a documented occurrence at least 3 months before randomisation of eGFR <60 mL/min/1.73 m2, UACR = 30 mg/g, and/or other markers of kidney damage (including urine protein dipstick =1+, positive urine albumin dipstick, or urinary protein to creatinine ratio =84 mg/g)
- Patients should receive background standard of care treatment for albuminuria and/or T2DM and be treated according to locally recognised guidelines, as appropriate. Guideline-recommended medications should
be used at recommended doses. Therapy should have been optimised and stable for =4 weeks before study entry and include an ACEi or anARB, unless contraindicated, not tolerated, or in the opinion of the investigator not practically available or suitable.
- If treated with a sodium-glucose transport protein (SGLT2) inhibitor, the SGLT2 inhibitor dose must have been stable for =4 weeks before randomisation.
- Meeting screening criteria for sUA and eGFR (Visit 2)
(a) sUA =6.0 mg/dL
(b) eGFR =25 mL/min/1.73 m2 (CKD-EPI formula)
- Mean UACR between 30 mg/g and 5000 mg/g inclusive. At least 2 first morning void samples collected before randomisation will be required.
- Male or female
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 425
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300
- Autosomal dominant or autosomal recessive polycystic kidney disease,
lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-
associated vasculitis
- History of renal transplantation
- Known carrier of the (HLA-B) *58:01 allele.
- Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan
syndrome
- 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 (NYHA) Class IV at the time of
randomisation
- QT interval corrected by the Fridericia formula (QTcF) >470 msec;
patients diagnosed with long QT syndrome; patients with a family
history of long QT syndrome
- Receiving cytotoxic therapy, 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 randomisation
- Treated with strong or moderate (OATP) inibitors
- Participation in another clinical study with an investigational product
administered during the last month prior to randomisation
- Patients who are pregnant, lactating, or planning to become pregnant.
- Left ventricular hypertrophy with the left ventricular septum exceeding 14 mm during diastole, assessed by echocardiogramm within 6 months of screening (Mozaffarian et al 2016, Shenasa and Shenasa 2017, Williams et al 2018)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effects of treatment with verinurad and allopurinol, allopurinol alone, and placebo on UACR at 6 months;Secondary Objective: To assess the effects of treatment with verinurad and allopurinol, allopurinol alone, and placebo on UACR at 12 months<br>To assess the effects of verinurad and allopurinol, allopurinol alone, and placebo on sUA<br>To estimate the dose-response relationship among 3 doses of verinurad and allopurinol and placebo on UACR and sUA<br>To assess the effects of verinurad and allopurinol versus placebo on kidney function.;Primary end point(s): Change from baseline in UACR at 6 months;Timepoint(s) of evaluation of this end point: From baseline at 6 months
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Change from baseline in UACR at 12 months, end of treatment and end of study<br>• Change from baseline in sUA at 6 and 12 months, end of treatment and end of study<br>• Change from baseline in estimated glomerular filtration rate at 6 and 12 months, end of treatment and end of study• Change from baseline in creatinine at 6 and 12 months, end of treatment and end of study<br>• Change from baseline in cystatin-C at 6 and 12 months end of treatment and end of study;Timepoint(s) of evaluation of this end point: • From baseline at 12 months, end of treatment and end of study<br>• From baseline at 6 and 12 months, end of treatment and end of study<br>• From baseline at 6 and 12 months, end of treatment and end of study<br>• From baseline at 6 and 12 months, end of treatment and end of study<br>• From baseline at 6 and 12 months, end of treatment and end of study