Phase 3 Trial of Bedtime Treatment, TNX-102 SL, Reaches Half Enrollment

Phase 3 Trial of Bedtime Treatment, TNX-102 SL, Reaches Half Enrollment

The RELIEF Phase 3 trial assessing the safety and efficacy of TNX-102 SL (sublingual cyclobenzaprine) as a nighttime treatment of pain and disturbed sleep due to fibromyalgia has reached half of its planned enrollment of patients, Tonix Pharmaceuticals announced.

Tonix anticipates sharing early treatment results in this first group of patients in September, but acknowledged that the COVID-19 pandemic may delay data monitoring and analysis.

The muscle relaxant cyclobenzaprine has the potential to block different receptors involved in pain, sleep, and stress regulation, being a promising approach to ease symptoms of fibromyalgia. Current oral formulations, however, are limited to short-term use due to liver toxicity, and exposure to active compounds that may result as cyclobenzaprine breaks down in the body.

TNX-102 SL is a reformulation of cyclobenzaprine, taken as sublingual (under the tongue) tablets. Tonix reports this formulation not only helps the active ingredient reach the bloodstream faster, but also results in limited toxicity to the liver, suggesting it can be used for longer periods.

The therapy was evaluated in a prior Phase 3 trial, named AFFIRM (NCT02436096), in 519 people with fibromyalgia. Enrolled across 35 sites in the U.S., participants were randomly assigned to either a 2.8 mg dose of TNX-102 SL tablets, or a placebo, given daily at bedtime for 12 weeks.

Results showed that TNX-102 SL’s use significantly improved sleep quality and reduced fatigue, but pain levels were not lower compared to the placebo.

Supported by these findings and data from previous studies of a higher dose (5.6 mg) in people with post-traumatic stress disorder, the company launched the RELIEF Phase 3 trial (NCT04172831) to investigate TNX-102 SL at that daily higher dose in fibromyalgia patients.

The trial is now recruiting up to 470 adults, ages 18 to 65, across 40 U.S. sites. All will be randomly assigned to TNX-102 SL or a placebo, both given daily for 14 weeks. Treatment will be taken at bedtime, at a 2.8 mg dose for the first two weeks, then increasing to 5.6 mg (two, 2.8 mg tablets) for the next 12 weeks.

RELIEF’s main goal is to investigate changes in pain from study’s start (baseline) to week 14, using weekly averages of patient-reported daily rating scores. Changes in functional capacity and global disease impact will be assessed as a secondary measure.

“TNX-102 SL is a potential new, non-opioid, non-addictive analgesic that has been shown to have activity at a syndromal level, improving a broad array of fibromyalgia symptoms in prior Phase 2 and Phase 3 studies at the 2.8 mg dose,” Seth Lederman, MD, president and CEO at Tonix, said in a press release.

“If the final results from this study are positive, we believe that TNX-102 SL could provide a distinct mechanism from available pharmacotherapies that makes a significant difference in the lives of patients with fibromyalgia,” Lederman added.

A preliminary analysis will be conducted by an Independent Data Monitoring Committee (IDMC) after the first half of randomized participants have completed treatment. The committee will review data to determine if the trial should continue enrolling as planned, whether more patients should be included, or if it should be stopped earlier — either because the treatment is a success or because it is not expected to bring benefits to patients.

Despite the ongoing pandemic, the trial remains on schedule to enroll another half of participants. Top-line data from the full study population is expected in early 2021, the company said.

Should results from RELIEF be positive, Tonix is planning to request regulatory approval for TNX-102 SL as a fibromyalgia treatment. Its application is expected to include data from the company’s PTSD program, demonstrating the long-term safety of TNX-102 SL at 5.6 mg in these patients.