The second Phase 3 clinical trial examining a higher dose of TNX-102 SL (sublingual cyclobenzaprine), Tonix Pharmaceuticals‘ bedtime treatment for managing fibromyalgia, is enrolling participants.
The RALLY trial (NCT04508621) is recruiting 470 adults with fibromyalgia, ages 18–65. Nearly 40 U.S. sites are enrolling, or will be. More information about contacts and locations is available here.
Tonix expects to report top-line data from this trial in the second half of 2021.
Meanwhile, early results are expected this month for the RELIEF trial (NCT04172831), the first Phase 3 study evaluating the 5.6 mg dose in fibromyalgia patients. The trial completed patient enrollment in July and top-line results are expected by year’s end, according to the company.
Pending positive results from both trials, Tonix expects to file a new drug application with the U.S. Food and Drug Administration in late 2022, seeking regulatory approval of TNX-102 SL as a treatment for fibromyalgia.
“This is an important milestone for Tonix and potentially for the nation’s roughly 8 million adult fibromyalgia [patients],” Seth Lederman, MD, president and CEO, said in a press release. “Our team is dedicated to advancing TNX-102 SL, which is being developed as a novel, non-opioid, non-addictive, centrally-acting analgesic.”
TNX-102 SL is a reformulation of cyclobenzaprine, a muscle relaxant with the potential to ease pain and stress, while also improving sleep. Yet, existing oral formulations of cyclobenzaprine can be used for only short periods due to liver toxicity.
The experimental therapy is taken as sublingual (under the tongue) tablets, which helps the active ingredient reach the bloodstream faster and results in limited toxicity to the liver. As such, it may be used for longer periods, Tonix says.
A 2.8 mg dose of this non-opioid therapy has been tested in the AFFIRM Phase 3 trial (NCT02436096). A total of 519 patients were assigned to either TNX-102 SL or a placebo, taken at bedtime for 12 weeks.
While TNX-102 SL significantly improved sleep quality and reduced fatigue, the treatment failed to lower pain levels, compared with the placebo.
However, a trial in post-traumatic stress disorder showed that a higher TNX-102 SL dose (5.6 mg) also was well-tolerated, leading Tonix to launch two additional Phase 3 trials testing this dose in fibromyalgia patients.
The first trial is RELIEF, which enrolled 470 patients across several clinical sites in the U.S. Participants were assigned randomly to receive daily TNX-102 SL or a placebo.
In the first two weeks, treatment will be taken at bedtime at a 2.8 mg dose. The dose will be increased to 5.6 mg (two 2.8 mg tablets) for the next 12 weeks.
The main goal is to determine whether TNX-102 SL significantly reduces self-reported pain over the trial’s 14 weeks. Changes in functional capacity and global disease impact will be assessed as secondary measures.
The second trial, RALLY, will be essentially similar to RELIEF. It will recruit the same number of participants, dose patients with TNX-102 SL or a placebo for 14 weeks, and also include a run-in period with a starting dose of 2.8 mg for two weeks. The treatment will be evaluated with the same outcome measures.
“Many people with fibromyalgia are still dissatisfied with available treatments. Tolerability can be a problem for some with the approved medications. Addiction can be a problem with off-label use of opiates,” said Lederman.
“TNX-102 SL has the potential to provide relief from the pain, fatigue, sleep disturbance and dysfunction from fibromyalgia with good tolerability and without addictive potential,” he said.