Abstract Introduction: Neuropathic pain (NP) management remains challenging owing to the suboptimal efficacy and short durability of current therapies. Poor clinical outcomes and persistent peripheral NP from lumbosacral radiculopathy (NP-LSR) highlight the need for novel pain management approaches. KLS-2031 is a novel gene therapy that uses recombinant adeno-associated virus serotype 5 vectors to deliver therapeutic genes directly to the dorsal root ganglion through a single transforaminal epidural injection. Objectives: To evaluate the safety, tolerability, and exploratory efficacy of KLS-2031 in patients with NP-LSR. Methods: In this first-in-human, randomized, placebo-controlled phase 1/2a study (double-blinded until week 52 and open-label extension through week 104; ClinicalTrials.gov: NCT04238793), 18 patients were randomized to receive KLS-2031 (n = 12, doses of 1 × 10 11 , 10 12 , and 10 13 VG/500 µL in cohorts 1, 2, and 3, respectively) or placebo (n = 6). Primary endpoints were safety and tolerability that were assessed through week 52. Results: KLS-2031 was well-tolerated across all dose levels, with no reports of mortality, serious treatment-emergent adverse events (TEAEs), or AE-related discontinuations. The proportion of patients experiencing drug-related TEAEs was comparable between the KLS-2031 and placebo groups. No clinically significant safety signals were observed in other safety assessments. Exploratory efficacy outcomes did not show a consistent trend favoring KLS-2031 over placebo. Conclusion: KLS-2031 demonstrated a favorable safety profile and tolerability in patients with NP-LSR, supporting the need for further studies to confirm its safety and efficacy.
Bertoch et al. (Wed,) studied this question.