Paradigm's Zilosul Phase 3 knee osteoarthritis trial falls below continuation threshold
核心洞察
An independent Data Safety Monitoring Board found the Phase 3 PARA_OA_012 trial of injectable pentosan polysulfate sodium fell below its predefined efficacy continuation threshold.
The interim analysis, conducted after about half of 538 participants reached the Day 112 primary endpoint, met the study's futility criterion.
Paradigm said operational problems caused substantial missing data that, under the statistical analysis plan, was imputed and affected the interim efficacy result.
Paradigm Biopharmaceuticals (搜索) reported that an independent Data Safety Monitoring Board found its Phase 3 knee osteoarthritis (搜索) trial, PARA_OA_012, fell below the efficacy threshold set in the study design, meeting the predefined futility criterion. The interim analysis was conducted after about half of the 538 enrolled participants reached the Day 112 primary efficacy endpoint, and the observed treatment effect fell short of the minimum required for continuation, suggesting the study is unlikely to meet its primary endpoint at final analysis. The board reviewed unblinded efficacy and safety data.
The trial is testing injectable pentosan polysulfate sodium, known as iPPS or Zilosul. Paradigm said operational problems in running the trial led to a significant amount of missing data, which affected the interim results; under the statistical analysis plan, missing data is imputed, and that imputation impacted the efficacy outcome. Executive Chairman Paul Rennie said the board and team were deeply disappointed, adding that the company remains optimistic about the therapeutic potential of PPS in osteoarthritis.
Paradigm will work with the monitoring board, clinical partners and investigators to determine remaining study activities and database processes, then conduct a detailed review of the Phase 3 data covering pain, function, safety and other predefined endpoints. The Zilosul osteoarthritis program holds Fast Track designation from the US Food and Drug Administration (搜索), but the company said it will reassess the timing, scope and objectives of future regulatory engagement after that review. The board is also examining wind-down costs, contractual commitments, future funding needs and obligations under its secured convertible note facility with Obsidian Global GP, LLC (搜索), and the company said it cannot yet quantify the full financial and operational impact.
Source: Biotech Dispatch