Efficacy and safety of Lenzumestrocel (Neuronata-R (R) inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial

Background: A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS. Methods: ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months. Discussion: Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.N