Tonix announces 12-week primary endpoint for Phase 3 RECOVERY study
Tonix Pharmaceuticals Holding announced that in the currently-enrolling Phase 3 study of Tonmya for the treatment of posttraumatic stress disorder, the timing of the primary endpoint analysis has been changed from Week 4 to Week 12 and the Company plans to add an interim analysis that allows for a potential sample size adjustment, based on guidance from its recent Breakthrough Therapy Type B Clinical Guidance meeting with the U.S. Food and Drug Administration. The Phase 3 study design changes are being implemented after the FDA indicated the importance of showing persistence of treatment effect at Week 12 in a pivotal study. In the revised protocol, the primary endpoint, mean change from baseline in the severity of PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5, will be assessed at Week 12 instead of Week 4. Week 12 measurement of CAPS-5 was the same timepoint measurement used for the primary endpoint in the previous Phase 3 HONOR and the Phase 2 AtEase studies of Tonmya for PTSD. In addition, the RECOVERY study will include an unblinded interim analysis that allows for a potential sample size re-estimation. It will be conducted when 50 percent of the current target number of participants are randomized and have either completed or discontinued the 12-week course of treatment with bedtime Tonmya or placebo sublingual tablets. The introduction of the potential sample size re-estimation was added to address the potential impact of more drop-outs between Week 4 and Week 12, since the study was originally powered for a Week 4 endpoint. The data will be reviewed by an Independent Data Monitoring Committee which will make a non-binding recommendation to the Company based on the unblinded interim analysis. Pending final approval by FDA, the planned interim analysis will have three possible recommendations: 1) keep the current sample size and continue as planned; 2) provide the opportunity to increase the sample size to include up to a maximum of 120 additional participants, based on certain criteria; and 3) stop the study early for futility. The proposed design will not include an option to stop for positive efficacy at the interim analysis. The proposed sample size re-estimation methodology maintains the statistical hurdle of p less than 0.05. If the current sample size is kept at 250 participants at the interim analysis, there will be no statistical penalty on average compared to the current design. With an increase in sample size, the results from the cohorts before and after the interim analysis will be averaged with equal weight and p less than 0.05 will still be required for success. This methodology has been successfully utilized in other pivotal studies and was a component of the Phase 3 HONOR study's interim analysis that was agreed to by the FDA. Since more than 125 participants have already been enrolled, the Company expects to report the results of the interim analysis and the recommendation of the IDMC in the first quarter of 2020. If the current projected population of 250 study participants remains unchanged, the Company expects to report topline data in the second quarter of 2020.