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

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ClinicalTrials.gov Identifier: NCT04632225
Recruitment Status : Recruiting
First Posted : November 17, 2020
Last Update Posted : May 19, 2021
Sponsor:
Information provided by (Responsible Party):
Helixmith Co., Ltd.

Tracking Information
First Submitted Date  ICMJE October 29, 2020
First Posted Date  ICMJE November 17, 2020
Last Update Posted Date May 19, 2021
Actual Study Start Date  ICMJE January 27, 2021
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: February 17, 2021)
  • 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)
  • 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
  • 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  ICMJE Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Biological: Engensis
    Lyophilized biologic to be reconstituted containing Engensis
  • Other: Placebo
    Injectable liquid
Study Arms  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 11, 2020)
18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Guzman 858-428-1225 ClinicalTrials@Helixmith.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04632225
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Helixmith Co., Ltd.
Study Sponsor  ICMJE Helixmith Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Helixmith Co., Ltd.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP