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NCT04632225: REViVALS-1A

Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Completed Phase 2 Results posted Last updated 6 October 2025
What this trial tests

Phase 2 trial testing Engensis in Amyotrophic Lateral Sclerosis in 18 participants. Completed in 15 July 2024.

Timeline
9 March 2021
Primary endpoint
11 July 2022
15 July 2024

Quick facts

Lead sponsorHelixmith Co., Ltd.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment18
Start date9 March 2021
Primary completion11 July 2022
Estimated completion15 July 2024
Sites5 locations across United States, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Helixmith Co., Ltd. — full company profile →

Who can join

Adults 18 to 80, any sex, with Amyotrophic Lateral Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety of Intramuscular Injections of Engensis in Participants With Amyotrophic Lateral Sclerosis Compared to Placebo Primary · From the Day 0 Visit to the Day 180 Visit

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.

Injection Site bruising
GroupValue95% CI
Engensis4
Placebo3
Pyrexia
GroupValue95% CI
Engensis3
Placebo1
Injection site pain
GroupValue95% CI
Engensis2
Placebo1
Asthenia
GroupValue95% CI
Engensis0
Placebo2
Fatigue
GroupValue95% CI
Engensis1
Placebo1
Arthralgia
GroupValue95% CI
Engensis2
Placebo0
Muscle spasms
GroupValue95% CI
Engensis1
Placebo1
Musculoskeletal stiffness
GroupValue95% CI
Engensis2
Placebo0
Changes in Muscle Function Following Engensis Injections Compared to Placebo Secondary · Day 0 to Day 180

Change from Baseline (Day 0) in total mean Revised Amyotrophic Lateral Sclerosis Function Rating scores, subscores for Fine and Gross Motor Functions and Bulbar Function, and slope of the total score. The Revised Amyotrophic Lateral Sclerosis Function Rating scores includes twelve questions that ask the physician to rate his/her impression of the patient's level of functional impairment in performing one of twelve common tasks e.g., climbing stairs). Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score

GroupValue95% CI
Engensis-5.9± 4.2
Placebo-4.2± 4.76
Evaluation of Muscle Strength Changes Following Engensis Injections Compared to Placebo - Hand-Held Dynamometry Secondary · Day 0 to Day 180

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 180 by Muscle Group (ITT Population)

Shoulder Flexion, left
GroupValue95% CI
Engensis-6.48± 8.317
Placebo-3.33± 1.552
Shoulder Flexion, right
GroupValue95% CI
Engensis-7.608± 9.2493
Placebo-2.100± 4.4234
Elbow Flexion, left
GroupValue95% CI
Engensis-10.562± 12.7571
Placebo-3.250± 4.4004
Elbow Flexion, right
GroupValue95% CI
Engensis-10.68± 11.813
Placebo-1.68± 3.174
Elbow Extension, left
GroupValue95% CI
Engensis-6.424± 11.0173
Placebo2.350± 1.1590
Elbow Extension, right
GroupValue95% CI
Engensis-6.83± 8.925
Placebo-1.08± 5.171
Wrist Extension, left
GroupValue95% CI
Engensis-7.162± 7.8940
Placebo4.943± 8.5556
Wrist Extension, right
GroupValue95% CI
Engensis-6.53± 10.081
Placebo-2.18± 4.350
Evaluation of Quality of Life Improvement Following Engensis Injections Compared to Placebo - Exploratory Outcome Secondary · Day 0 to Day 84, and Day 0 to 180

The Amyotrophic Lateral Sclerosis Assessment Questionnaire has 40 items (ALSAQ-40), and is a standardized Quality of Life assessment. The Participant completes the 40 questions in the 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. T

Day 84 - Physical Mobility
GroupValue95% CI
Engensis1.88± 20.255
Placebo-1.5± 5.755
Day 180 - Physical Mobility
GroupValue95% CI
Engensis13.44± 24.014
Placebo11.88± 17.366
Day 84 - Activities of Daily Living/Independence
GroupValue95% CI
Engensis10.31± 9.396
Placebo0.50± 8.178
Day 180 - Activities of Daily Living/Independence
GroupValue95% CI
Engensis15.94± 17.369
Placebo11.25± 12.332
Day 84 - Eating and Drinking
GroupValue95% CI
Engensis8.34± 12.596
Placebo11.66± 21.732
Day 180 - Eating and Drinking
GroupValue95% CI
Engensis17.73± 18.623
Placebo14.58± 21.886
Day 84 - Communication
GroupValue95% CI
Engensis11.15± 24.334
Placebo7.14± 13.363
Day 180 - Communication
GroupValue95% CI
Engensis24.56± 27.690
Placebo11.60± 25.977
Evaluation of Patient Reported Outcome Improvement Following Engensis Injections Compared to Placebo Secondary · Day 84 and Day 180 (End of Study or Early Termination)

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 diff

Day 84
GroupValue95% CI
Engensis3.1± 1.81
Placebo4.6± 0.89
End of Study / Early Term- Day 180
GroupValue95% CI
Engensis2.9± 1.46
Placebo4.0± 2.00
Evaluation of Clinical Reported Outcome Improvement Following Engensis Injections Compared to Placebo Secondary · Day 84 to Day 180

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 from 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 84 and 180/ Early Termination.

Day 84 - Minimally improved
GroupValue95% CI
Engensis2
Placebo3
Day 84 - Minimally worse
GroupValue95% CI
Engensis5
Placebo1
Day 84 - No change
GroupValue95% CI
Engensis3
Placebo2
End Study/Early term- Minimally improved
GroupValue95% CI
Engensis0
Placebo1
End Study/Early term- Minimally worse
GroupValue95% CI
Engensis4
Placebo0
End Study/Early term- Much worse
GroupValue95% CI
Engensis2
Placebo1
End Study/Early term- No change
GroupValue95% CI
Engensis4
Placebo2
To Determine Effects of Engensis on Respiratory Function Compared to Placebo - Slow Vital Capacity Secondary · Day 0 to Day 180

Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation, and was to be measured at Screening, pre-dose on Days 60 and 120, and on Days 30, 84, 144, and 180.

Day 30
GroupValue95% CI
Engensis-3.31± 4.191
Placebo2.53± 7.501
Day 60 (pre-dose)
GroupValue95% CI
Engensis-6.50± 9.439
Placebo-3.90± 9.173
Day 84
GroupValue95% CI
Engensis-6.50± 11.808
Placebo-2.3± 9.182
Day 120 (pre-dose)
GroupValue95% CI
Engensis-12.76± 13.363
Placebo-8.84± 12.916
Day 144
GroupValue95% CI
Engensis-13.46± 17.605
Placebo-9.04± 15.925
Day 180
GroupValue95% CI
Engensis-17.80± 17.308
Placebo-1.75± 10.046
To Determine Effects of Engensis on Respiratory Function Compared to Placebo - Tracheostomy Secondary · Day 0 to Day 180

Total Participants that experienced Tracheostomy during the study in the Intent-to-treat population.

GroupValue95% CI
Engensis0
Placebo0
To Determine Effects of Engensis on Survival Compared to Placebo - Deaths Secondary · Day 0 to Day 180

Participants that died during the study, for all causes including Treatment Emergent Adverse Events, or Treatment Emergent Serious Adverse Events, leading to study discontinuation, or study drug withdrawal in any subject.

GroupValue95% CI
Engensis0
Placebo0

Adverse events — posted to ClinicalTrials.gov

Time frame: From Day 0 to Day 180 or Early Termination. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Engensis
Serious: 1/12 (8%)
Deaths: 0/12
Placebo
Serious: 0/6 (0%)
Deaths: 0/6

Serious adverse events (1 terms)

ReactionSystemEngensisPlacebo
BronchitisInfections and infestations
Other adverse events (21 terms — click to expand)

ReactionSystemEngensisPlacebo
COVID-19Infections and infestations
Injection site bruisingGeneral disorders
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Injection site painGeneral disorders
AstheniaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Muscle contractions involuntaryNervous system disorders
RhinorrheaRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Joint range of motion decreasedMusculoskeletal and connective tissue disorders
DysarthriaNervous system disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
InsomniaPsychiatric disorders
HypertensionVascular disorders

Most-reported serious reactions: Bronchitis.

Data from ClinicalTrials.gov NCT04632225 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation.
    Mead RJ, Shan N, Reiser HJ, Marshall F, et al · · 2023 · cited 323× · PMID 36543887 · DOI 10.1038/s41573-022-00612-2
  2. Amyotrophic lateral sclerosis: translating genetic discoveries into therapies.
    Akçimen F, Lopez ER, Landers JE, Nath A, et al · · 2023 · cited 162× · PMID 37024676 · DOI 10.1038/s41576-023-00592-y
  3. New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022.
    Jiang J, Wang Y, Deng M. · · 2022 · cited 48× · PMID 36518658 · DOI 10.3389/fphar.2022.1054006
  4. Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.
    Maragakis NJ, de Carvalho M, Weiss MD. · · 2023 · cited 21× · PMID 37641443 · DOI 10.1002/acn3.51887
  5. Advanced Gene-Targeting Therapies for Motor Neuron Diseases and Muscular Dystrophies.
    Chamakioti M, Karantzelis N, Taraviras S. · · 2022 · cited 11× · PMID 35563214 · DOI 10.3390/ijms23094824
  6. The Advent of Omics Sciences in Clinical Trials of Motor Neuron Diseases.
    Ruffo P, Cavallaro S, Conforti FL. · · 2022 · cited 8× · PMID 35629180 · DOI 10.3390/jpm12050758
  7. Genetic and Mechanistic Insights Inform Amyotrophic Lateral Sclerosis Treatment and Symptomatic Management: Current and Emerging Therapeutics and Clinical Trial Design Considerations.
    Quigley SE, Quigg KH, Goutman SA. · · 2025 · cited 2× · PMID 40897992 · DOI 10.1007/s40263-025-01217-0
  8. Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential.
    Li A, Yi J, Li X, Dong L, et al · · 2022 · cited 2× · PMID 36291129 · DOI 10.3390/cells11203263

Verify or expand the search:

Other trials of Engensis

Trials testing the same drug.

Other recruiting trials for Amyotrophic Lateral Sclerosis

Currently open trials in the same condition.

Other Helixmith Co., Ltd. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04632225.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing