Keenova's XIAFLEX hits pain endpoint in first pivotal trial for Ledderhose disease
The Phase 3 STRIDE trial met its primary pain endpoint and key secondary measures, positioning Keenova to file the first drug application for plantar fibromatosis in the fourth quarter of 2026.
Executive Summary
- A pivotal trial of an already-approved collagenase drug met its primary pain endpoint and several ranked secondary endpoints in a connective-tissue foot condition that currently has no approved pharmacological treatment.
- The sponsor plans to file for FDA approval within months, which would be the first drug approval specifically for this indication rather than another off-label or surgical option.
- The announcement reports statistical significance across the primary pain measure and function scales along with a safety profile consistent with the drug's known record, but the topline release does not carry effect size or numerical detail.
- The trial's completion date shifted twice during conduct, a pattern common to studies with drawn-out visit schedules, while final enrollment landed within the range the drug's operator has typically achieved across its broader trial portfolio.
The result
Keenova Therapeutics plc announced on July 8, 2026 that its Phase 3 EN3835-309 trial, known as STRIDE, met its primary endpoint: a statistically significant improvement in average daily foot pain, measured on a numeric rating scale, at Week 12 versus placebo. The trial also met ranked secondary endpoints tied to difficulty and activity limitation on the Foot Function Index scale, and additional secondary measures, including the FFI pain subscale, global assessments of disease severity and improvement, treatment satisfaction, and nodule characteristics, also showed statistically significant improvement. The registered primary outcome measure is the change from baseline to Week 12 in the weekly mean of average daily pain intensity on the numeric rating scale. Keenova+1Keenova Announces Positive Phase 3 Results in Clinical Trial of XIAFLEX® (collagenase clostridium histolyticum) for Treating Plantar FibromatosisJul 8, 2026Study to Assess EN3835 in the Treatment of Plantar Fibromatosis (Also Known as Ledderhose Disease)NCT06151197
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The design
STRIDE was a double-blind, placebo-controlled trial that enrolled 436 adults with plantar fibromatosis, each with at least one measurable fibrous nodule on clinical exam. Participants were randomized to XIAFLEX or placebo, with each arm receiving up to two treatments spaced at least 28 days apart. Pain was captured daily via patient diary, alongside periodic assessments including the Foot Function Index, Patient Global Impression of Severity, and Patient Global Impression of Change. The trial registered one primary and eleven secondary endpoints and ran from November 2023 through completion in June 2026. Keenova+1Keenova Announces Positive Phase 3 Results in Clinical Trial of XIAFLEX® (collagenase clostridium histolyticum) for Treating Plantar FibromatosisJul 8, 2026Study to Assess EN3835 in the Treatment of Plantar Fibromatosis (Also Known as Ledderhose Disease)NCT06151197
Safety and what's disclosed
Keenova said the safety profile was consistent with XIAFLEX's known profile from its existing approved indications, with most adverse events rated mild to moderate by investigators and no treatment-related serious adverse events reported. The company's own statement, quoting Dr. Marek Honczarenko, its chief scientific officer, frames the data as clearing the bar for filing: "With these results, we intend to submit our application for this indication to the FDA in the fourth quarter of 2026". The release does not carry the numerical effect size, confidence interval, or p-value behind the "statistically significant" language, so the topline characterization stands until fuller data post. KeenovaKeenova Announces Positive Phase 3 Results in Clinical Trial of XIAFLEX® (collagenase clostridium histolyticum) for Treating Plantar FibromatosisJul 8, 2026
What it changes
XIAFLEX is currently approved by the FDA for urological and orthopedic conditions, and Keenova frames plantar fibromatosis as an indication where treatment today is limited to orthotics, topical agents, steroid injections, radiation, or surgery, with no approved drug therapy. A positive pivotal result in that setting would make this the first drug specifically positioned for regulatory approval in the indication, extending an approved molecule into a new disease area rather than introducing a new mechanism. The competitive field around this specific trial and drug shows no other program sharing its target or mechanism class in active development for this indication. KeenovaKeenova Announces Positive Phase 3 Results in Clinical Trial of XIAFLEX® (collagenase clostridium histolyticum) for Treating Plantar FibromatosisJul 8, 2026
Operational context
The trial's primary completion date moved twice before finishing, from November 2025 to March 2026, and then to June 2026, before the study reached Completed status on July 13, 2026. Enrollment was finalized at 436 participants, up from an interim count of 418, a change the operational model characterizes as within its routine band for a completed Phase 3 study. The trial operator has an 88% overall completion rate across 89 prior trials, providing sponsor-level execution context for the study's eventual completion. NCT06151197Study to Assess EN3835 in the Treatment of Plantar Fibromatosis (Also Known as Ledderhose Disease)NCT06151197
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.