Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

NCT04632225 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: VMALS-002-2
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study was to evaluate the safety of intramuscular administration of Engensis in Participants with Amyotrophic Lateral Sclerosis as compared to Placebo. Safety will be assessed by incidences of treatment-emergent adverse events, treatment-emergent serious adverse events, injection site reactions and other adverse events of special interest, and the clinically significant laboratory values after injections of Engensis compared to Placebo. Exploratory endpoints include assessment of muscle function using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale subscores for Fine and Gross Motor Function; muscle strength by quantitative testing using handheld dynamometry and the Accurate Test of Limb Isometric Strength where available; quality of life using the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40; patient global impression of change, clinical global impression of change, and clinical global impression of severity; and evaluation of lung function using Slow Vital Capacity. Muscle biopsies will be performed during the study for future biomarker analyses.

Conditions

Amyotrophic Lateral Sclerosis

Outcome Measures

Primary Outcomes (1)

• Safety of Intramuscular Injections of Engensis in Participants With Amyotrophic Lateral Sclerosis Compared to Placebo

  Incidence of treatment-emergent adverse events in more than or equal to 10% of subjects, and treatment-emergent serious adverse events after injections, injection site reactions, and clinically significant laboratory values for Engensis compared to Placebo.

  From the Day 0 Visit to the Day 180 Visit

Other Outcomes (9)

• Changes in Muscle Function Following Engensis Injections Compared to Placebo

  Day 0 to Day 180

• Evaluation of Muscle Strength Changes Following Engensis Injections Compared to Placebo - Hand-Held Dynamometry

  Day 0 to Day 180

• Evaluation of Muscle Strength Changes Following Engensis Injections Compared to Placebo - Accurate Test of Limb Isometric Strength

  Day 0 to Day 180

Study Arms (2)

Engensis

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Engensis BIOLOGICAL

Lyophilized biologic to be reconstituted containing Engensis

Engensis

Placebo OTHER

Injectable liquid

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically definite or probable Amyotrophic Lateral Sclerosis or laboratory-supported probable Amyotrophic Lateral Sclerosis as defined in the revised El Escorial/Airlie House diagnostic criteria
• The site of onset of Amyotrophic Lateral Sclerosis symptoms is a limb and experiencing symptoms of lower motor dysfunction (e.g., weakness, atrophy, cramps, poor circulation, etc.) with upper motor neuron symptoms (e.g., weakness, brisk reflexes, spasticity)
• Onset of Amyotrophic Lateral Sclerosis symptoms ≤ 4 years
• Slow Vital Capacity ≥ 50% of predicted value at Screening
• Not taking riluzole, or on a stable dose (defined as no noted toxicities) for at least 30 days prior to Screening and throughout the study
• Not taking edaravone or on a maintenance cycle for at least 30 days prior to Screening and throughout the study
• For females of childbearing potential, a negative urine pregnancy test at Screening and on Day 0
• Male Participants and their female partners must agree to use double-barrier contraception during the study or provide proof of postmenopausal state (minimum 1 year) or surgical sterility
• Male Participants must not donate sperm during the study
• Female Participants must be nonpregnant, nonlactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or agree to use double-barrier contraception from 28 days prior to randomization (Day 0) and/or their last confirmed menstrual period prior to study randomization (whichever is longer) until the end of the study
• Capable of complying and willing to comply with the requirements and restrictions in the informed consent form and this protocol
• Willing to forgo new experimental Amyotrophic Lateral Sclerosis treatments for at least 6 months following randomization

You may not qualify if:

• Progressive or degenerative neurological disorder such as Alzheimer's disease, Parkinson's disease, vascular dementia, multiple sclerosis, and other neurological or vascular disorders felt by the Investigator to preclude participation
• Requires tracheotomy ventilation or noninvasive ventilation related to bulbar function
• Evidence by physical examination, history, or laboratory evaluation of significant concomitant disease with a life expectancy of \< 6 months at Screening
• International Normalized Ratio values \>2.0
• Platelet count \<100,000/µL
• Inflammatory disorder of the blood vessels (inflammatory angiopathy or vasculitis, such as Buerger's disease)
• Active infection (chronic infection or severe active infection that may compromise the Participant's wellbeing or participation in the study in the Investigator's judgment)
• Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)
• Positive human immunodeficiency virus or human T-cell lymphotrophic virus I/II test at Screening
• Active acute or chronic hepatitis B
• Active hepatitis C
• Immunosuppression due to underlying disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) or to currently receiving immunosuppressive drugs, (e.g., chemotherapy, corticosteroids) or to radiation therapy
• Stroke or myocardial infarction within 3 months prior to Screening
• Active deep vein thrombosis
• Recent history (\< 3 years) or presence of cancer except basal cell carcinoma or squamous cell carcinoma of the skin that was excised and has shown no evidence of recurrence for at least 1 year

Sponsors & Collaborators

• Helixmith Co., Ltd.: lead

Study Sites (5)

St. Joseph's Hospital and Medical Center, Barrows Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University Department of Neurology

Baltimore, Maryland, 21205, United States

Location

Austin Neuromuscular Center

Austin, Texas, 78759, United States

Location

Hanyang University Medical Center

Seoul, 04763, South Korea

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Jinsub Lee, PhD.
• Organization: Helixmith Co, Ltd.

jinsub.lee@helixmith.com

+82-10-8256-0439

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 17, 2020
• Study Start: March 9, 2021
• Primary Completion: July 11, 2022
• Study Completion: July 15, 2024
• Last Updated: October 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-08

Locations

US (4); KR (1)