The Premature Termination of the Phase III SALAMANDER Trial of REX-001, an Autologous Bone Marrow Cell Therapy, for Chronic Limb Ischemia in Diabetic Patients: Insights and Outcomes.

BACKGROUND

To evaluate the efficacy and safety of REX-001, an autologous bone marrow-derived mononuclear cell product, in patients with chronic limb-threatening ischemia (CLTI) who had no options for revascularization.

METHODS

In this multicenter, double-blind, randomized, placebo-controlled phase III clinical trial, diabetic patients with CLTI (Rutherford category 5), no revascularization options, and no urgent need for amputation were enrolled. Bone marrow (250 mL) was processed to create REX-001, and a single intra-arterial injection was administered. Primary endpoints included change in Rutherford classification (to category 4 or lower) or complete ulcer healing within 12 months. Secondary endpoints included limb TcpO2, ulcer size, quality of life, ankle-brachial index, 6-min walking test, and amputation-free survival.

RESULTS

The trial was stopped early after an interim analysis of 50% of the patients due to lack of efficacy. Thirty-two patients completed the study (21 REX-001, 11 placebo). Complete ulcer healing or improvement in Rutherford category occurred in 28.6% of REX-001-treated patients and 27.3% of placebo-treated patients. No treatment-related adverse events or safety concerns were identified. Data on secondary endpoints were not available.

CONCLUSION

This prematurely ended study failed to confirm REX-001's efficacy for ulcer healing. Nevertheless, the study provides valuable insights into trial design, endpoint selection, and data stewardship, guiding future regenerative therapy research in this challenging patient population.