A 6-Month Extension Study to Assess the Long-Term Safety of Engensis in Amyotrophic Lateral Sclerosis (REViVALS-1B)

A 6-Month Extension Study to Assess the Long-Term Safety of Engensis in Amyotrophic Lateral Sclerosis

A 6-Month Extension Study Following Protocol VMALS-002-2 (A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis)

The purpose of this study is to evaluate the long-term safety of intramuscular (IM) administration of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) who were previously randomized, received treatment, and completed the Day 180 Visit of Study VMALS-002-2. Safety will be assessed by incidences of treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), adverse events of special interest (AESIs), and the clinically significant laboratory values. See the table below for additional, exploratory endpoints.

Active Comparator: Engensis 64 mg Engensis per Treatment Cycle, with each of 3 cycles composed of 2 days of 128 injections each to the right and left target muscles, spaced 2 weeks apart

Placebo Comparator: Placebo 32 mL of Placebo per Treatment Cycle, with each of 3 cycles composed of 2 days of 128 injections each to the right and left target muscles, spaced 2 weeks apart

• To evaluate the long-term safety of intramuscular (IM) injections of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS)

• Changes from Baseline (Study VMALS 002-2 Day 0) in Revised Amyotrophic Lateral Sclerosis Function Rating (ALSFRS-R) scores at Day 365 for Engensis compared to Placebo

• Change from Baseline (Study VMALS 002-2 Day 0) in muscle strength assessed bilaterally by Handheld Dynamometry (HHD) in muscles in the upper and lower extremities at Day 365 for Engensis compared to Placebo

• To determine whether IM administration of Engensis has effects on respiratory capacity in ALS Participants

• Change from Baseline (Study VMALS 002-2 Day 0) in Slow Vital Capacity (SVC) at Day 365 for Engensis compared to Placebo

• To determine whether IM administration of Engensis has effects on respiratory function in ALS Participants

• To determine whether IM administration of Engensis has positive effects on survival in ALS Participants

• To evaluate Quality of Life improvement following Engensis injections in ALS Participants compared to Placebo

• Change from Baseline (Day 0) in Quality of Life (QoL) using the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ; with 40 items, ALSAQ 40) on Day 365 for Engensis compared to Placebo

• To evaluate Patient Reported Outcome improvement following Engensis injections in ALS Participants compared to Placebo

• To evaluate Clinician Reported Outcome improvement following Engensis injections in ALS Participants compared to Placebo

Inclusion Criteria: Participants who complete the Day 180 Visit in VMALS-002-2 are eligible to enroll in this extension study, VMALS-002-2b. Exclusion Criteria: - None