Bone to Optimize Phase 2b Trial of High-Risk Tibial Fracture Cell Therapy
The adjustments come after the company announced a reprioritization to focus on ALLOB in September 2021.
Bone Therapeutics has made adjustments to optimize their phase 2b trial (NCT04432389) of their allogeneic osteoblast cell therapy, ALLOB, for high-risk tibial fractures.1
The changes include turning a secondary endpoint into a primary endpoint and adding an interim analysis. Bone will also implement optimized statistical analyses based on recently published medical data that should allow required patient enrollment to be reduced by 20%. Bone will submit the changes for regulatory approval shortly.
“Bone Therapeutics’ ALLOB represents a significant opportunity for clinical unmet medical needs in bone regeneration namely difficult tibial fractures. These affect more than 300.000 patients per year in US and EU alone and can have a significant impact to the lives of those affected,” Anne Leselbaum, MD, chief medical officer, Bone Therapeutics, said in a statement.1 “The improved statistical analysis derived from emerging clinical data, will more precisely document the potential benefit of ALLOB over standard practice alone in difficult tibial fractures and could become a reference for future clinical trial objectives and endpoints.”
The randomized, double-blind, placebo-controlled phase 2b study is assessing ALLOB, in combination with standard of care stabilization surgery, in accelerating fracture healing and preventing late-stage complications at 3 and 6 months in patients with high-risk tibial fractures. ALLOB is administered via a single percutaneous injection within 24-96 hours after definitive reduction surgery in patients with fresh tibial fractures at risk of delayed or non-union. The trial, which is approved in 7 European countries, is currently enrolling patients in over 40 sites.
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ALLOB has previously demonstrated good tolerability with some evidence of clinical benefit in around 60 patients in phase 1/2 trials (NCT02020590). Investigators have observed evidence of increased bone formation and other clinical benefits.
Bone Therapeutics has improved the statistical analysis in the study based off of “new information on timing and dynamics of radiological evidence of fracture resolution in recently published medical data”, although these data were not cited.1 The updated analysis should provide an optimal radiological assessment of bone formation acceleration and will be carried over to phase 3 trials. The analysis also converts a current secondary endpoint to a primary endpoint and allows the trial to maintain the same statistical power while enabling a reduction of approximately 20% of the required patient numbers from 178 patients to 132 evaluable patients.
An independent Data and Safety Monitoring Board (DSMB) will evaluate the new interim analysis at 3 months and could recommend completing the study early for efficacy if the targeted, more stringent interim efficacy level in bone healing has been achieved. Bone Therapeutics is planning to report topline results and DSMB recommendations after the interim analysis as scheduled by the first half of 2023.
“The current operational focus of Bone Therapeutics on the conduct of the study aims at ensuring the delivery of top line data as scheduled by the first half of 2023. With the inclusion of the interim analysis, we gain an opportunity to evaluate the efficacy of ALLOB at a slightly earlier time in 2023 and to potentially advance its development to the next stage,” Leselbaum added.1
Bone Therapeutics previously shifted their focus to ALLOB in September 2021 after disappointing results were observed in their phase 3 study (NCT04333160) of JTA-004 for the treatment of osteoarthritic knee pain.2 JTA-004 is a next-generation intra-articular injectable that consists of a unique mix of hyaluronic acid, plasma proteins, and a fast-acting analgesic. The study’s secondary end point, a statistically significant difference in pain reduction at month 3 between JTA-004 and Hylan G-F 20, also failed. However, a subanalysis of patients with higher pain scores at entry did show a statistically significant difference in favor of JTA-004 and Hylan G-F 30 compared to placebo.
