Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis (REViVALS-1A)

• ClinicalTrials.gov Identifier: NCT04632225
• Recruitment Status: Completed
• First Posted: November 17, 2020
• Last Update Posted: November 7, 2022
• Sponsor: Helixmith Co., Ltd.
• Information provided by (Responsible Party): Helixmith Co., Ltd.

Tracking Information

• First Submitted Date: October 29, 2020
• First Posted Date: November 17, 2020
• Last Update Posted Date: November 7, 2022
• Actual Study Start Date: February 9, 2021
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2021)

Safety of intramuscular (IM) injections of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) compared to Placebo [ Time Frame: From the Day 0 Visit to the Day 180 Visit ]

Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) after injections, injection site reactions, and clinically significant laboratory values for Engensis compared to Placebo

Original Primary Outcome Measures (submitted: November 11, 2020)

Safety of intramuscular (IM) injections of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) compared to Placebo [ Time Frame: From the Day 0 Visit to the Day 180 Visit ]

Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) after injections, injection site reactions, and clinically significant laboratory values after injections of Engensis compared to Placebo

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: June 30, 2022)

• Changes in muscle function following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  Change from Baseline (Day 0) in total mean Revised Amyotrophic Lateral Sclerosis Function Rating (ALSFRS-R) scores, subscores for Fine and Gross Motor Functions and Bulbar Function, and slope of the total score
• Evaluation of muscle strength changes following Engensis injections compared to Placebo - HHD [ Time Frame: Day 0 to Day 180 ]
  As assessed bilaterally by Hand-Held Dynamometry (HHD) in muscles in the upper and lower extremities
• Evaluation of muscle strength changes following Engensis injections compared to Placebo - ATLIS [ Time Frame: Day 0 to Day 180 ]
  As assessed bilaterally by the Accurate Test of Limb Isometric Strength (ATLIS) where available
• Evaluation of Quality of Life improvement following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed using the ALS Assessment Questionnaire with 40 items (ALSAQ-40)
• Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo - PGIC [ Time Frame: Day 84 to Day 180 ]
  As assessed using the Patient Global Impression of Change (PGIC)
• Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo - CGIC [ Time Frame: Day 84 to Day 180 ]
  As assessed using the Clinical Global Impression of Change (CGIC)
• To determine effects of Engensis on respiratory function compared to Placebo - SVC [ Time Frame: Day 0 to Day 180 ]
  As assessed using Slow Vital Capacity (SVC)
• To determine effects of Engensis on respiratory function compared to Placebo - Tracheostomy [ Time Frame: Day 0 to Day 180 ]
  As assessed by time to tracheostomy
• To determine effects of Engensis on survival compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  Time to all-cause mortality
• Comparing gene expression differences in muscle atrophy biomarkers between subjects receiving Engensis and subjects receiving Placebo by using RNA sequencing [ Time Frame: Day 0 to Day 180 ]
  Using RNA sequencing methods to obtain genome transcription profiles of the group receiving Engensis and the group receiving Placebo, and compare the gene expression differences between these two groups

Original Other Pre-specified Outcome Measures (submitted: November 11, 2020)

• Changes in muscle function following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  Change from Baseline (Day 0) in total mean Revised Amyotrophic Lateral Sclerosis Function Rating (ALSFRS-R) scores, subscores for Fine and Gross Motor Functions and Bulbar Function, and slope of the total score
• Evaluation of muscle strength changes following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed bilaterally by Hand-Held Dynamometry (HHD) in muscles in the upper and lower extremities
• Evaluation of muscle strength changes following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed bilaterally by the Accurate Test of Limb Isometric Strength (ATLIS) where available
• Evaluation of Quality of Life improvement following Engensis injections compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed using the ALS Assessment Questionnaire with 40 items (ALSAQ-40)
• Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo [ Time Frame: Day 84 to Day 180 ]
  As assessed using the Patient Global Impression of Change (PGIC)
• Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo [ Time Frame: Day 84 to Day 180 ]
  As assessed using the Clinical Global Impression of Change (CGIC)
• Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo [ Time Frame: Day 84 to Day 180 ]
  As assessed using the Clinical Global Impression of Severity (CGIS)
• To determine effects of Engensis on respiratory function compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed using Slow Vital Capacity (SVC)
• To determine effects of Engensis on respiratory function compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  As assessed by time to tracheostomy
• To determine effects of Engensis on survival compared to Placebo [ Time Frame: Day 0 to Day 180 ]
  Time to all-cause mortality

Descriptive Information

• Brief Title: Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis
• Official Title: A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis
• Brief Summary: The purpose of this study is to evaluate the safety of intramuscular (IM) administration of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) as compared to Placebo. Safety will be assessed by incidences of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), injection site reactions (ISRs) and other adverse events of special interest (AESIs), 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 (ALSFRS-R) and ALSFRS-R subscores for Fine and Gross Motor Function; muscle strength by quantitative testing using handheld dynamometry (HHD) and the Accurate Test of Limb Isometric Strength (ATLIS) where available; quality of life using the ALS Assessment Questionnaire (ALSAQ-40); patient global impression of change (PGIC), clinical global impression of change (CGIC), and clinical global impression of severity (CGIS); and evaluation of lung function using Slow Vital Capacity (SVC). Muscle biopsies will be performed during the study for future biomarker analyses.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• Biological: Engensis
  Lyophilized biologic to be reconstituted containing Engensis
• Other: Placebo
  Injectable liquid

Study Arms

• 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
  Intervention: Biological: Engensis
• 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
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 11, 2020): 18
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 31, 2022
• Actual Primary Completion Date: July 11, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Clinically definite or probable Amyotrophic Lateral Sclerosis (ALS) or laboratory-supported probable ALS as defined in the revised El Escorial/Airlie House diagnostic criteria
2. The site of onset of ALS 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)
3. Onset of ALS symptoms ≤ 4 years
4. Slow Vital Capacity (SVC) ≥ 50% of predicted value at Screening
5. 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
6. Not taking edaravone or on a maintenance cycle for at least 30 days prior to Screening and throughout the study
7. For females of childbearing potential, a negative urine pregnancy test at Screening and on Day 0
8. 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
9. Male Participants must not donate sperm during the study
10. 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
11. Capable of complying and willing to comply with the requirements and restrictions in the informed consent form and this protocol
12. Willing to forgo new experimental ALS treatments for at least 6 months following randomization

Exclusion Criteria:

1. 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
2. Requires tracheotomy ventilation or noninvasive ventilation related to bulbar function
3. Evidence by physical examination, history, or laboratory evaluation of significant concomitant disease with a life expectancy of < 6 months at Screening
4. INR values >2.0
5. Platelet count <100,000/µL
6. Inflammatory disorder of the blood vessels (inflammatory angiopathy or vasculitis, such as Buerger's disease)
7. 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)
8. Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)
9. Positive human immunodeficiency virus (HIV) or human T-cell lymphotrophic virus (HTLV) I/II test at Screening
10. Active acute or chronic hepatitis B
11. Active hepatitis C
12. 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
13. Stroke or myocardial infarction within 3 months prior to Screening
14. Active deep vein thrombosis
15. 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
16. 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
17. Use of an investigational drug for the treatment of ALS in the past 30 days or 5 half-lives (if available), whichever is longer, or previous participation in a clinical study with Engensis
18. Stem cell administration for investigational treatment of ALS or other conditions in the 6 months prior to Screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of, United States

Administrative Information

• NCT Number: NCT04632225
• Other Study ID Numbers: VMALS-002-2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Helixmith Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Helixmith Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Helixmith Co., Ltd.
• Verification Date: November 2022