Janssen Ends Canagliflozin CREDENCE Trial Early After Hitting T2D, CKD Endpoints
JULY 16, 2018
Vlado Perkovic, PhDJanssen Pharmaceutical Companies of Johnson & Johnson have announced an early end to a phase 3 of canagliflozin (Invokana) for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), due to its achieving pre-specified efficacy criteria.
The Canagliflozin and Renal Events in Diabetes with Established Neuropathy Clinical Evaluation (CREDENCE) trial, a comparative study of the efficacy and safety of canagliflozin versus placebo, has been concluded on the basis of a planned interim data analysis.
Based on a recommendation from an independent data monitoring committee (IDMC), Janssen opted to end the trial when it was found that it had already reached pre-specified criteria for its primary composite endpoint of end-stage kidney disease—as measured by time to dialysis or kidney transplantation—the doubling of serum creatinine, and renal or cardiovascular death.
Canagliflozin was provided to patients as an additional therapy to standard-of-care treatment.
CREDENCE—the first trial dedicated to a therapy background to standard-of-care measuring renal outcomes in patients with CKD and T2D—was a randomized, double-blind, placebo controlled study involving multiple clinical centers. It enrolled about 4400 patients with T2D, with estimated glomerular filtration rate (eFGR) ≥30 to <90 mL/min/1.73 m2, and albuminuria.
All participating patients were on maximum labeled or tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blockers (ARBs) for more than 4 weeks prior to randomization.
The significance of preventive therapies for patients with T2D at risk for CKD is emphasized by the patient population size. Vlado Perkovic, PhD, CREDENCE Steering Committee co-chair and professor of medicine at University of New South Wales Sydney, said in a statement that nearly half of all people with T2D will develop CKD and put them at risk for worsening disease, despite current best available care.
“This huge unmet need is why it was so important for us to initiate the landmark CREDENCE renal outcomes trial over four years ago,” Perkovic said. “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.”
The month leading up to the sudden end of CREDENCE was a notable time for canagliflozin. New data from the CANVAS and CANVAS-R trials, presented at the 2018 American Diabetes Association’s 78th Annual Scientific Sessions in Orlando, FL, reported the therapy was associated a reduced risk of sustained kidney function lost, decline in eFGR, and reduction in albuminuria versus placebo.
Canagliflozin was also shown to not increase the risk of below-knee amputation in patients with T2D when compared to other anti-hyperglycemic therapies, despite previously having a boxed warning added to its label to indicate a risk of leg and foot amputations.
James List, MD, PhD, global therapeutic area head of Cardiovascular & Metabolism, Janssen Research & Development, said the full data from the CREDENCE trial will be presented at an upcoming medical meeting “and with health authorities in the near future.”
“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,” List said.