Safety Study of VM202 to Treat Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of intramuscular injections of VM202 at different injection sites in people with amyotrophic lateral sclerosis.

Detailed Description
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A phase I/II, open label, single center study designed to assess the safety and tolerability of intramuscular injections of VM202 inpatients with ALS. Study enrollment will be staged. Enrollment will be halted after the sixth subject qualifies for treatment. A Data Safety Monitoring Board (DSMB) will conduct a safety evaluation after the first patient treated completes the Day 60 follow-up evaluation and the five other sequentially enrolled subjects complete at least the Day 30 follow-up. Enrollment will be suspended until a formal recommendation to proceed (or not proceed) is made by the DSMB. Patients aged ≥ 21 years, but ≤ 75 years diagnosed with clinically definite, clinically probable, or clinically probable-laboratory supported Amyotrophic Lateral Sclerosis (ALS). This study is not powered to detect differences in efficacy measures. However, descriptive statistics (N, mean, median, SD, minimum and maximum values, where applicable) of clinically meaningful endpoints will be tabulated

Official Title
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A Phase I/II, Open Label Study to Assess the Safety and Tolerability of VM202 in Subjects With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: VM202


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21 years, but < or = 75 years Subjects diagnosed with: clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as specified in the revised El Escorial / Airlie House diagnostic criteria Onset of ALS < 2 years at Screening Forced Vital Capacity (FVC) ≥ 60% of predicted Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) ≥ 30 Not taking riluzole, or on a stable dose for at least thirty days prior to Screening (defined as no noted toxicities) Able and willing to give informed consent If female of childbearing potential, negative urine pregnancy test at Screening and using acceptable method of birth control during the study. Exclusion Criteria: Neurological symptom(s) due to vitamin B12 deficiency Requires tracheotomy ventilation or noninvasive ventilation > 16 hours / day Comorbidities such as Parkinson's disease, schizophrenia, renal failure, or any other severe complication that, in the Investigator's opinion, will compromise the safety of the patient or confound interpretation of the data collected in this study Other neuromuscular disease Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease) Active infection Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis) Positive HIV or HTLV at Screening Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAb), antibody to Hepatitis B surface antigen (IgG and IgM; HBsAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV) at Screening Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy or radiation therapy Stroke or myocardial infarction within last 3 months Patients with a recent history (< 5 years) of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); Subjects requiring > 81 mg daily of acetylsalicylic acid; subjects may be enrolled if willing/able to switch to ≤ 81 mg daily of acetylsalicylic acid or to another medication Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (excepting inhaled steroids); subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs for the duration of the study Have used an investigational drug within 30 days of Screening Pregnant or currently lactating Major psychiatric disorder in past 6 months Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or who in the opinion of the Investigator are not suitable to participate.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VM202<br>Total dose of 64 mg of VM202 It will be administered over the course of four visits: Day 0, Day 7, Day 14, and Day 21. As in all previous VM202 studies, final dose of VM202 for each target muscle group is divided and administered 2 weeks apart. | Biological: VM202<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serious and Non Serious Adverse Events | Adverse events (including serious adverse events, and adverse events leading to treatment discontinuation) throughout the 9 months follow-up. Descriptive statistics will be used to characterize safety parameters. | Throughout the nine month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | The Amyotrophic Lateral Sclerosis Function Rating Scale includes twelve questions that ask the physician to rate his/her impression of the patient's level of functional impairment in performing one of twelve common tasks (e.g., climbing stairs). Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0 = worst and 48 = best. | Screening, on Day 0 before the treatment (injection), on Day 30, Day 60, Day 90, at 6 months and 9 months | 
| Change in Mean Muscle Strength Medical Research Council (MRC) Scores | The Medical Research Council (MRC) Scale is a validated instrument used in assessing muscle strength. It uses the numeral grades 0-5 to characterize muscle strength as follows: 0 - No contraction;1 - Flicker or trace contraction; 2 - Active movement, with gravity eliminated; 3 - Active movement against gravity; 4 - Active movement against gravity and resistance; 5 - Normal power The MRC scale was used to assess muscle strength in the muscle groups injected with Engensis. | Day 0, Day 30, Day 60, Day 90, at 6 months and 9 months | 
| Change From Baseline (Day 0) in Forced Vital Capacity (%) | pulmonary function test that quantifies the volume of air that can forcibly be blown out after full inspiration. It correlates with survival in ALS | Day 30, Day 60, Day 90, at 6 months and 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, Lou Gehrig's disease, neurodegenerative disease