The steering committee behind the phase 3 CREDENCE clinical trial, evaluating the efficacy and safety of the SGLT2 inhibitor canagliflozin vs. placebo for adults with type 2 diabetes and chronic kidney disease, announced an early stop of the trial based on the achievement of prespecified efficacy criteria, according to a press release from Janssen.
The decision is based on a recommendation from the study’s independent data monitoring committee that met to review the data during a planned interim analysis, according to Janssen. This recommendation was based on demonstration of efficacy with canagliflozin (Invokana), as the trial had achieved prespecified criteria for the primary composite endpoint of end-stage renal disease, doubling of serum creatinine, and renal or cardiovascular death, when used in addition to standard of care.
“Nearly half of all people with type 2 diabetes will develop chronic kidney disease, causing a high risk of kidney failure and cardiovascular disease, and impacting their quality and length of life, even with the current best available care,” Vlado Perkovic, MBBS, PhD, FASN, FRACP, CREDENCE steering committee co-chair, professor of medicine at University of New South Wales Sydney and executive director of The George Institute for Global Health in Australia, said in a statement. “This huge unmet need is why it was so important for us to initiate the landmark CREDENCE renal outcomes trial over 4 years ago. We have accepted the advice of the independent data monitoring committee to stop the CREDENCE trial early due to demonstration of efficacy and look forward to sharing the findings as soon as possible.”
As Endocrine Today previously reported, the CREDENCE trial, originally estimated to be completed by 2020, was designed to assess whether canagliflozin has a renal and vascular protective effect in reducing the progression of renal impairment relative to placebo in participants with type 2 diabetes, stage 2 or 3 CKD and macroalbuminuria. The trial enrolled approximately 4,400 patients with type 2 diabetes and an estimated glomerular filtration rate between 30 mL/min/1.73 m2 and 90 mL/min/1.73 m2, and albuminuria, defined as a urinary albumin to creatinine ratio between 300 mg/g and 5,000 mg/g. All patients were required to be on the maximum labeled or tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers for more than 4 weeks prior to randomization.
“Chronic kidney disease is a progressive condition that impacts a person’s overall health and well-being, and with millions of people worldwide suffering from the disease, we know that there is a clear need for new treatment options,” James List, MD, PhD, global therapeutic area head for cardiovascular and metabolism at Janssen Research and Development, said in a statement. “We are excited about the possibility of bringing forth Invokana as the first therapy to treat patients with chronic kidney disease and type 2 diabetes in more than 15 years. We look forward to presenting the full data from the CREDENCE trial at an upcoming medical meeting and with health authorities in the near future.”
Canagliflozin is currently contraindicated for patients with severe renal impairment, defined as eGFR of less than 30 mL/min/1.73 m2, ESRD or patients on dialysis. Additionally, canagliflozin is not recommended in patients with an eGFR that is persistently lower than 45 mL/min/1.73 m2.
In a presentation at the second annual Heart in Diabetes Clinical Education Conference in Philadelphia on July 14, Mark E. Cooper, MD, PhD, professor of diabetes and head of the department of diabetes, Central Clinical School at Monash University in Melbourne, Australia, noted that SGLT2 inhibitors have shown the most promise with respect to renal benefits — the most interesting finding being an observed stabilization of eGFR in patients with diabetic kidney disease.
In the CANVAS study, patients with type 2 diabetes at high risk for CVD assigned canagliflozin saw a 33% reduction in risk for hospitalization for heart failure and were 40% less likely to experience renal decline vs. those assigned placebo, Cooper said.
“The data are robust that SGLT2 inhibitors are clearly renoprotective, and I think this will turn out to be a class effect,” Cooper said during the presentation. – by Regina Schaffer