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

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 administration of Engensis in Participants with Amyotrophic Lateral Sclerosis 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, treatment emergent serious adverse events, adverse events of special interest, and the clinically significant laboratory values.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: Engensis; Other: Placebo

Detailed Description

VMALS-002-2b was a safety extension study following VMALS-002-2, which was a Phase 2a, double-blind, randomized, placebo-controlled, multicenter study designed to assess the safety of intramuscular administration of Engensis in subjects with Amyotrophic Lateral Sclerosis.Following completion of the Day 180 visit in VMALS-002-2 and signing of written informed consent, subjects were enrolled in this approximately 180-day extension study, with subjects completing combined participation with a Day 365 visit. Assessments to be conducted during this extension study were as follows: vital signs, weight and height, complete physical examination, 12-lead electrocardiogram, a record of all concomitant medications and procedures, clinical laboratory assessments, Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, handheld dynamometry, slow vital capacity, Amyotrophic Lateral Sclerosis Assessment Questionnaire, 40 questions, Patient Global Impression of Change, and Clinical Global Impression of Change. Assessments of treatment-emergent adverse events, treatment-emergent serious adverse events, adverse events of special interest, and clinically significant laboratory values continued from the Day 180 visit of Study VMALS-002-2 through the VMALS-002-2b extension study to Day 365.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea, 04763
    • Hanyang University Medical Center
• United States
  • Texas
    • Austin, Texas, United States, 78759
      • Austin Neuromuscular Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Engensis; 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	Biological: Engensis; Lyophilized biologic to be reconstituted containing Engensis
Placebo Comparator: Placebo; 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	Other: Placebo; Injectable Liquid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term	To evaluate the long-term safety of intramuscular injections of Engensis in Participants with Amyotrophic Lateral Sclerosis in more than 2 Participants by System Organ Class and Preferred Term (Safety Analysis Population)	Day 0 to Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants	Changes from Baseline (Study VMALS 002-2, Day 0) in Revised Amyotrophic Lateral Sclerosis Function Rating TOTAL scores at Day 365 for Engensis compared to Placebo There are 12 separate assessments in this neuromuscular assessment covering Bulbar, Fine Motor, Gross Motor and Breathing assessments. Each individual assessment is scored from 0 (worst case) to 4 (best case). Total score is calculated as the sum of all 12 assessment subscores. Note that only the Total Score will be reported in the clinical study report due to the small number of subjects. The Total Score range is from a minimum of 0 (worst case) to a maximum of 48 (best case).	Day 0 and Day 365
To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants	As assessed bilaterally by Hand-Held Dynamometry in muscles in the upper and lower extremities. Muscle Strength as Measured by Handheld Dynamometry (lbs.) and Change from Baseline to Day 365 by Muscle Group (ITT Population)	Day 0 and Day 365
To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants	Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation. It is measured in Liters of air and the percentage of change from baseline is the Percent Predicted Value and Change from Baseline. Change from Baseline (Study VMALS 002-2, Day 0) in Slow Vital Capacity on Day 240, Day 300 and Day 365 for Participants with intramuscular administration of Engensis compared to Placebo. Increasing negative Change from Baseline results indicates worsening of respiratory capacity.	Day 0, Day 240, Day 300 and Day 365
To Determine if Intramuscular Engensis Has Effects on Respiratory Function in Amyotrophic Lateral Sclerosis Participants - Tracheostomy	Total participants requiring Tracheostomy procedures that received intramuscular administration of Engensis, compared to total Placebo participants requiring Tracheostomy procedures.	Day 0 to Day 365
To Determine if Intramuscular Administration of Engensis Has Positive Effects on Survival in Amyotrophic Lateral Sclerosis Participants - All-Cause Mortality	Total all-cause Mortality for participants that received intramuscular injections of Engensis, compared to total all-cause Mortality for Placebo participants. Total participant deaths that received intramuscular administration of Engensis, compared to total Placebo participant deaths.	Day 0 to Day 365
To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo	The Participant completes the 40 questions in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with 5 categories: Physical Mobility, Activities of Daily Living and Independence, Eating and Drinking, Communication, and Emotional Reactions. Each question has 5 responses to select from: 0-Never (Best Case), 1-Rarely, 2-Sometime, 3-Often, and 4-Always (Worst Case). Note for each question there is a Minimum of 0 (Best), to the Maximum 4 (Worst). Decreasing scores indicates improvement of symptoms. The Total Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) scores are per Category as percentages of 100% maximum. Each Category percentage is summed for the Intent-to-treat Population. The Change from Baseline was calculated and displayed in the Table. ALSAQ-40 was completed at the pre-dose baseline visit (Day 0), and at the Day 240 and Day 365 visits.	Day 0, Day 240 and Day 365
To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo	The subject's impression of change after treatment was measured with the Patient Global Impression of Change questionnaire through use of the electronic Patient Reported Outcome . This questionnaire measures the subject's perception of how treatment has affected their level of activity, symptoms, emotions, and overall quality of life. Each descriptor is ranked on an increasing improvement scale; where 1 = No change (or condition has got worse), 2=Almost the same, hardly any change at all, 3=A little better, but no noticeable change, 4=Somewhat better, but the change has not made any real difference, 5=Moderately better, and a slight but noticeable change, 6=Better, and a definite improvement that has made a real and worthwhile difference, and 7 = A great deal better, and a considerable improvement that as made all the difference. The test was self-administered on Days 240 and 365.	Day 240 and Day 365
To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo	The Clinical Global Impression of Change is a validated instrument completed by observers as an assessment of Quality of Life. The Clinical Global Impression of Change is an 8-point scale with scores ranging rom Marked Improvement, Moderate Improvement, Minimal Improvement, Slight Improvement, and Unchanged (or Worse), along with an efficacy index with questions in a matrix for therapeutic effect and side effects.The test was completed on Days 240 and 365/ Early Termination.	Day 240 and Day 365

Collaborators and Investigators

• Sponsor: Helixmith Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2021
• Primary Completion (Actual): December 29, 2022
• Study Completion (Actual): August 23, 2024

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: VMALS-002-2b

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No