Amyotrophic Lateral SclerosisPhase 2REViVALS-1ANCT04632225
Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis
A Phase 2 study testing Engensis in people with Amyotrophic Lateral Sclerosis, run by Helixmith Co., Ltd. at 5 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Engensis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 9 Mar 2021to 15 Jul 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
- Major psychiatric disorder diagnosed in the past 6 months that has not been stabilized or in the Investigator's opinion would not allow the patient to participate in the scheduled procedures
- Use of an investigational drug for the treatment of Amyotrophic Lateral Sclerosis in the past 30 days or 5 half-lives (if available), whichever is longer, or previous participation in a clinical study with Engensis
- Stem cell administration for investigational treatment of Amyotrophic Lateral Sclerosis or other conditions in the 6 months prior to Screening
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Austin Neuromuscular Center
Austin, Texas, 78759
Johns Hopkins University Department of Neurology
Baltimore, Maryland, 21205
Northwestern University
Chicago, Illinois, 60611
St. Joseph's Hospital and Medical Center, Barrows Neurological Institute
Phoenix, Arizona, 85013
About this study
Official title: 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 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.
Read the detailed description
VMALS-002-2 was a controlled study to evaluate the safety of intramuscular administration of Engensis to subjects with Amyotrophic Lateral Sclerosis, as compared to Placebo. Subjects randomly assigned to Engensis were to receive a total dose of 192 mg Engensis divided into 3 treatment cycles of 64 mg Engensis each. A dosing schedule developed from those used in the Phase 1/2 Amyotrophic Lateral Sclerosis study and in three diabetic peripheral neuropathy studies were used in this study. The intramuscular injections to each target muscle group were divided into three Injection Visits (equal halves), two weeks apart on Days 0, and 14, with retreatment at Days 60 and 74, and Days 120 and 134. Engensis was delivered in a solution of 0.5 mg VM202/mL.
Results from this Phase 1/2 study suggest that targeted delivery of hepatic growth factor to motor neurons via intramuscular injections of Engensis was safe and well tolerated, based on data from 18 enrolled subjects who were followed through 90 days after the first injection [Sufit et al., 2017]. Following injections until Day 90, a plateau or a relative slowing in decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale scores and muscle strength was noted, suggesting a slowing of disease progression. After 90 days, the plateau was no longer observed in the Amyotrophic Lateral Sclerosis Functional Rating Scale, with the notable exception of a trend toward better preservation of bulbar and breathing functions as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale subscore, which appeared to persist out to 180 days. The change in Amyotrophic Lateral Sclerosis Functional Rating Scale total score over time or "slope" (>0, indicating clinical stability or improvement) following Engensis treatment was greatest at 2 months in 50% of subjects. At 3 months following Engensis, this improvement was observed in 25% of subjects. Muscle strength was stable for the first 3 months following Engensis administration and then steadily declined in both upper and lower limbs at subsequent months.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Engensis, Placebo
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EngensisBiological
Lyophilized biologic to be reconstituted containing Engensis
PlaceboOther
Injectable liquid
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the Day 0 Visit to the Day 180 Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start9 Mar 2021
- Primary completion11 Jul 2022
- Study completion15 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helixmith Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04632225
- Sponsor's protocol ID
- VMALS-002-2
- Acronym
- REViVALS-1A
- Status last verified
- Aug 2025
- First submitted
- 29 Oct 2020
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT04632225
- Acronym / sponsor ID
- REViVALS-1A / VMALS-002-2
- Conditions
- Amyotrophic Lateral Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Helixmith Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 15 Jul 2024 (actual)
- First posted
- 17 Nov 2020 (actual)
- Results
- Posted 6 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
VMALS-002-2 was a controlled study to evaluate the safety of intramuscular administration of Engensis to subjects with Amyotrophic Lateral Sclerosis, as compared to Placebo. Subjects randomly assigned to Engensis were to receive a total dose of 192 mg Engensis divided into 3 treatment cycles of 64 mg Engensis each. A dosing schedule developed from those used in the Phase 1/2 Amyotrophic Lateral Sclerosis study and in three diabetic peripheral neuropathy studies were used in this study. The intramuscular injections to each target muscle group were divided into three Injection Visits (equal halves), two weeks apart on Days 0, and 14, with retreatment at Days 60 and 74, and Days 120 and 134. Engensis was delivered in a solution of 0.5 mg VM202/mL.
Results from this Phase 1/2 study suggest that targeted delivery of hepatic growth factor to motor neurons via intramuscular injections of Engensis was safe and well tolerated, based on data from 18 enrolled subjects who were followed through 90 days after the first injection [Sufit et al., 2017]. Following injections until Day 90, a plateau or a relative slowing in decline of the Amyotrophic Lateral Sclerosis Functional Rating Scale scores and muscle strength was noted, suggesting a slowing of disease progression. After 90 days, the plateau was no longer observed in the Amyotrophic Lateral Sclerosis Functional Rating Scale, with the notable exception of a trend toward better preservation of bulbar and breathing functions as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale subscore, which appeared to persist out to 180 days. The change in Amyotrophic Lateral Sclerosis Functional Rating Scale total score over time or "slope" (>0, indicating clinical stability or improvement) following Engensis treatment was greatest at 2 months in 50% of subjects. At 3 months following Engensis, this improvement was observed in 25% of subjects. Muscle strength was stable for the first 3 months following Engensis administration and then steadily declined in both upper and lower limbs at subsequent months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Engensis | Active comparator | Biological: Engensis64 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 | Placebo comparator | Other: Placebo32 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EngensisLyophilized biologic to be reconstituted containing Engensis | Biological | Engensis |
| PlaceboInjectable liquid | Other | Placebo |
Primary outcome
Safety of Intramuscular Injections of Engensis in Participants With Amyotrophic Lateral Sclerosis Compared to Placebo
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Engensis in people with Amyotrophic Lateral Sclerosis, run by Helixmith Co., Ltd. at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Intramuscular Injections of Engensis in Participants With Amyotrophic Lateral Sclerosis Compared to Placebo (time frame: From the Day 0 Visit to the Day 180 Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.