Tonix Pharmaceuticals is halting its Phase III clinical trial of Tonmya in military related posttraumatic stress disorder (PTSD).
Tonix Pharmaceuticals, Inc., based in New York City, announced it was halting its Phase III HONOR clinical trial of Tonmya (cyclobenzaprine HCL sublingual tablets) in military related posttraumatic stress disorder (PTSD).
An Independent Data Monitoring Committee (IDMC) reviewed the results of the first 50 patients in the trial and recommended the trial be halted based on a pre-set 12-week study continuation threshold. The committee found that at the 12-week point, PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) between those on the drug and those receiving placebo had “inadequate separation.”
However, “meaningful improvement in overall PTSD symptoms was observed at week 4,” the company stated.
The HONOR study looked at 550 people with PTSD at 40 different sites in the U.S. A formal unblinded interim analysis was finished when about half of the partcipants were randomized and completed the 12-week course of treatment with either Tonmya or placebo. The primary efficacy endpoint was the 12-week mean change from baseline in the severity of PTSD symptoms as measured by CAPS-5.
At week 4, the group receiving Tonmya “separated from placebo in CAPS-5 (p = 0.019) and in the Clinical Global Impression-Improvement (CGI-K) scale (p = 0.015), a key secondary endpoint. Also, at week 4, sleep quality improved as measured by both the PROMIS sleep disturbance scale and the CAPS-5 sleep disturbance item, supporting the proposed mechanism of action of Tonyma,” the company stated.
PTSD affects about 11 million adults in the U.S., and is characterized by chronic disability, inadequate treatments options, especially for military-related PTSD, and high use of healthcare services.
Cyclobenzaprine is a muscle relaxant sold under the brand names of Amrix, Comfort Pac with Cyclobenzaprine, Fexmid and Flexeril. It is typically used to treat pain or skeletal muscle injuries.
Tonix had reported positive top-line results from its Phase II AtEase Study in 2016. The primary endpoint was the same as for the Phase III trial, but was at two different doses, 2.8mg or 5.6mg compared to placebo in 231 patients with military-related PTSD.
At that time, patients receiving the 2.8mg dose “trended toward the direction of therapeutic effect, however,” MPR writes, “it failed to reach statistical significance on the primary endpoint (p = 0.090). In contrast, treatment with the 5.6mg achieved therapeutic effect as assessed by the CAPS-5 and demonstrated statistical significance (p = 0.038), although patients in this arm included half of the patients in the 2.8mg arm.”
In the HONOR trial, patients were receiving 5.6mg dosages or a placebo.
“We are encouraged by the meaningful clinical improvement at week 4, which replicates findings in the previously-reported Phase II AtEase Study,” said Seth Lederman, president and chief executive officer of Tonix, in a statement. “We believe the results from the HONOR study will help to design the next pivotal study. We plan to meet with the FDA as soon as possible to discuss the HONOR results and our proposal to conduct the primary analysis at the week-4 time point in the next pivotal study. These results underscore the challenges in designing and conducting well-controlled clinical studies in PTSD, especially military-related PTSD.”
