Tenax Therapeutics is pausing new enrollment in its Phase 3 LEVEL-2 trial to narrow who gets in, a direct response to the failed LEVEL trial that missed its primary endpoint by 3.5 meters on the 6-minute walk distance test, a result so flat the p-value came in at 0.63. Rather than shelve the program, the company is betting that the LEVEL data contain a signal worth chasing: a subset of patients who, by that trial’s evidence, were most likely to show improved exercise tolerance.
The move is a protocol enrichment, not a redesign. Tenax plans to amend LEVEL-2’s enrollment criteria to concentrate on that patient subgroup, which the company believes gives the trial its best chance of hitting the same primary endpoint LEVEL missed. The 8-K filed with the SEC describes the pause as temporary, timed to let the amended criteria take effect before sites resume screening. The investor presentation attached to the filing carries the specifics of who qualifies under the new criteria, though the filing body does not spell out the exact demographic or hemodynamic cutoffs that define the enriched population.
TNX-103 is an oral levosimendan that works by activating ATP-sensitive potassium channels to drive splanchnic venodilation, reducing pulmonary capillary wedge pressure in patients with pulmonary hypertension due to heart failure with preserved ejection fraction, a condition where off-label steroids and diuretics remain the practical standard of care. The mechanism is pharmacologically plausible for a targeted population, which is exactly the argument enrichment strategies require: that the overall population diluted a real effect rather than proving the drug inert.
Tenax reported $118 million in cash as of June 30, 2026, with a projected runway through at least the second quarter of 2028, enough to fund LEVEL-2 through completion even with the enrollment delay this pause will introduce. The concrete marker to watch is the profile of patients Tenax actually enrolls once sites reopen: if the amended criteria draw the subgroup the company identified from LEVEL, the design logic holds; if enrollment drifts back toward a broad HFpEF population, the enrichment rationale weakens before a single efficacy read.
Source link: https://www.sec.gov/Archives/edgar/data/34956/000119312526417939/d139658d8k.htm
TNX-103: the facts in one place
- Also written: oral levosimendan
- Sponsor: Tenax Therapeutics, Inc.
- Mechanism: K-ATP channel activator and calcium sensitizer
- Indication studied: pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF)
- Phase: Phase 3
- Enrollment: 540
- Primary endpoint: change from baseline in 6-minute walk distance (6MWD) at Week 26 (LEVEL-2); 6MWD at Week 12 (LEVEL)
- Headline result: LEVEL trial did not meet primary endpoint; 3.5-meter difference vs placebo in overall population (p=0.63); prespecified subgroup with baseline 6MWD below 333 meters showed 26.3-meter improvement (nominal p=0.0112)
- Registry identifier: NCT05983250, NCT07288398
- Current status: LEVEL-2 Phase 3 trial enrollment paused as of October 8, 2026 to amend enrollment criteria; sponsor intends to request Type C Meeting with FDA to discuss registrational development revisions
- LEVEL topline results announced: August 10, 2026
- LEVEL-2 enrollment pause: October 8, 2026
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
