Clinical trial NCT02039401: Safety Study of VM202 to Treat Amyotrophic Lateral Sclerosis
Official title: A Phase I/II, Open Label Study to Assess the Safety and Tolerability of VM202 in Subjects With Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
Lou Gehrig's disease
neurodegenerative disease
Lead sponsor: Helixmith Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2014-01-17
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: A phase I/II, open label, single center study designed to assess the safety and tolerability of intramuscular injections of VM202 inpatients with Amyotrophic Lateral Sclerosis. Study enrollment will be staged. Enrollment will be halted after the sixth subject qualifies for treatment. A Data Safety Monitoring Board 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 Data Safety Monitoring Board.

Patients aged ≥ 21 years, but ≤ 75 years diagnosed with clinically definite, clinically probable, or clinically probable-laboratory supported Amyotrophic Lateral Sclerosis.

This study is not powered to detect differences in efficacy measures. However, descriptive statistics (N, mean, median, standard deviation, minimum and maximum values, where applicable) of clinically meaningful endpoints will be tabulated

Eligibility criteria: Inclusion Criteria:

* Age ≥ 21 years, but \< or = 75 years
* Subjects diagnosed with:

  * clinically definite Amyotrophic Lateral Sclerosis,
  * clinically probable Amyotrophic Lateral Sclerosis, or
  * clinically probable-laboratory supported Amyotrophic Lateral Sclerosis as specified in the revised El Escorial / Airlie House diagnostic criteria
* Onset of ALS \< 2 years at Screening
* Forced Vital Capacity ≥ 60% of predicted
* Revised Amyotrophic Lateral Sclerosis Functional Rating Scale ≥ 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, antibody to Hepatitis B surface antigen (IgG and IgM), Hepatitis B surface antigen and Hepatitis C antibodies 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.

Primary outcomes:
measure: Number of Subjects With Serious and Non Serious Adverse Events
timeFrame: Throughout the nine month follow up
Secondary outcomes:
measure: The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)
timeFrame: Screening, on Day 0 before the treatment (injection), on Day 30, Day 60, Day 90, at 6 months and 9 months
measure: Change in Mean Muscle Strength Medical Research Council (MRC) Scores
timeFrame: Day 0, Day 30, Day 60, Day 90, at 6 months and 9 months
measure: Change From Baseline (Day 0) in Forced Vital Capacity (%)
timeFrame: Day 30, Day 60, Day 90, at 6 months and 9 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University Stem Cell Institute
name: John A Kessler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sufit RL, Ajroud-Driss S, Casey P, Kessler JA. Open label study to assess the safety of VM202 in subjects with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017 May;18(3-4):269-278. doi: 10.1080/21678421.2016.1259334. Epub 2017 Feb 6.