Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

— REViVALS-1A  

Official title:

A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04632225
• Other study ID #: VMALS-002-2
• Status: Completed
• Phase: Phase 2
• Start date: February 9, 2021
• Est. completion date: August 31, 2022

Study information

• Verified date: November 2022
• Source: Helixmith Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 31, 2022
• Est. primary completion date: July 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Biological:
• Engensis
Lyophilized biologic to be reconstituted containing Engensis

Other:
• Placebo
Injectable liquid

Locations

Country	Name	City	State
Korea, Republic of	Hanyang University Medical Center	Seoul
United States	Austin Neuromuscular Center	Austin	Texas
United States	Johns Hopkins University Department of Neurology	Baltimore	Maryland
United States	Northwestern University	Chicago	Illinois
United States	St. Joseph's Hospital and Medical Center, Barrows Neurological Institute	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Helixmith Co., Ltd.

Countries where clinical trial is conducted

United States,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in muscle function following Engensis injections compared to Placebo	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	Day 0 to Day 180
Other	Evaluation of muscle strength changes following Engensis injections compared to Placebo - HHD	As assessed bilaterally by Hand-Held Dynamometry (HHD) in muscles in the upper and lower extremities	Day 0 to Day 180
Other	Evaluation of muscle strength changes following Engensis injections compared to Placebo - ATLIS	As assessed bilaterally by the Accurate Test of Limb Isometric Strength (ATLIS) where available	Day 0 to Day 180
Other	Evaluation of Quality of Life improvement following Engensis injections compared to Placebo	As assessed using the ALS Assessment Questionnaire with 40 items (ALSAQ-40)	Day 0 to Day 180
Other	Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo - PGIC	As assessed using the Patient Global Impression of Change (PGIC)	Day 84 to Day 180
Other	Evaluation of Patient and Clinical Reported Outcome improvement following Engensis injections compared to Placebo - CGIC	As assessed using the Clinical Global Impression of Change (CGIC)	Day 84 to Day 180
Other	To determine effects of Engensis on respiratory function compared to Placebo - SVC	As assessed using Slow Vital Capacity (SVC)	Day 0 to Day 180
Other	To determine effects of Engensis on respiratory function compared to Placebo - Tracheostomy	As assessed by time to tracheostomy	Day 0 to Day 180
Other	To determine effects of Engensis on survival compared to Placebo	Time to all-cause mortality	Day 0 to Day 180
Other	Comparing gene expression differences in muscle atrophy biomarkers between subjects receiving Engensis and subjects receiving Placebo by using RNA sequencing	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	Day 0 to Day 180
Primary	Safety of intramuscular (IM) injections of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) compared to Placebo	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	From the Day 0 Visit to the Day 180 Visit