Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: Engensis
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically definite or probable Amyotrophic Lateral Sclerosis (ALS) or laboratory-supported probable ALS as defined in the revised El Escorial/Airlie House diagnostic criteria 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) Onset of ALS symptoms ≤ 4 years Slow Vital Capacity (SVC) ≥ 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 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 ALS treatments for at least 6 months following randomization Exclusion Criteria: 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 INR values >2.0 Platelet count <100,000/µL Inflammatory disorder of the blood vessels (inflammatory angiopathy or vasculitis, such as Buerger's disease) 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 (HIV) or human T-cell lymphotrophic virus (HTLV) 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 ALS 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 ALS or other conditions in the 6 months prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Engensis<br>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 | Biological: Engensis<br>* Lyophilized biologic to be reconstituted containing Engensis<br>|
| Placebo Comparator: Placebo<br>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 | Other: Placebo<br>* Injectable liquid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |