The company aims to assess CardiAMP in patients with NT-proBNP over 500 pg/ml at baseline with a modified composite efficacy endpoint.
BioCardia has completed enrollment in its phase 3 trial (NCT02438306) of CardiAMP in patients with heart failure with reduced ejection fraction and is initiating discussions with the FDA to create a second study protocol with modified endpoints of the trial after it was previously announced that the primary endpoint was unlikely to be reached.1,2
“Together with our clinical partners, we have completed enrollment in the largest autologous cell therapy study for heart failure ever performed, with no treatment emergent safety concerns from the DSMB and interim results with both improved survival and reduced MACCE in the treatment group,” Peter Altman, PhD, chief executive officer, BioCardia , said in a statement.1 “Our world-class clinical leadership is supportive of pursuing the compelling and consistent interim results for patients with elevated NT-pro B-Type Natriuretic Peptide (BNP) at baseline. The data supports that if we had focused on this subset of patients with the updated composite endpoint, we should have met the primary endpoint in the study. With FDA alignment on the plan forward, we intend to secure the means required for the second study through the established Medicare reimbursement and partnering.”
BioCardia previously announced that the trial was unlikely to meet its primary, composite efficacy endpoint in July 2023, partly because both randomized study groups were experiencing good outcomes. At the time, the company also paused enrollment in the trial and continued to collect blinded data, which has since been unblinded.3
“Based on an analysis of the trial data, the primary Finkelstein and Schoenfeld composite endpoint assessment and a supplemental analysis presented on 7/19/23, unrelated to any emergent safety events, the DSMB recommends pausing new patient enrollment and any potential crossover patient procedures pending an outcomes analysis of patients currently completing the 1-year follow-up as well as the patients completing their imminently scheduled treatment,” a previous data safety monitoring board (DSMB) recommendation stated.3 “The DSMB recommends notifying currently enrolled patients completing their treatment sequence that the trial will be paused following their scheduled treatment to assess intermediate study results. The DSMB recommends the blind not be broken at this time to protect the integrity of the outcomes yet to be collected and to ensure that the study may be restarted without compromise after completion of the 1-year data analysis.”
There have been no treatment-emergent safety concerns by the DSMB. BioCardia pointed to slight signs of efficacy in the trial so far, including a 37% relative risk reduction of cardiac death equivalents and an 18% relative risk reduction in major adverse cardiac and cerebrovascular events (MACCE) in patients followed up for up to 24 months.1 The company plans to target a subset of patients with higher levels of NT-proBNP in which greater effect was observed. In patients with NT-pro BNP levels greater than 500 pg/ml at baseline, the company states that there was a 59% relative risk reduction in mortality over the control group and a 54% relative risk reduction of MACCE over the control group. Other clinical outcomes that favored CardiAMP included quality-of-life measurements and measures of cardiovascular health.
The proposed second study protocol includes the requirement that all patients have an NT-proBNP over 500 pg/ml at baseline and has a modified, composite primary endpoint consisting of all-cause death, the cardiac death equivalents of heart transplant and left ventricular assist device implantation, heart failure hospitalizations, worsening heart failure events treated as an outpatient, and change in quality-of-life with follow-up of 12 to 24 months.