Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, Lou Gehrig's disease, neurodegenerative disease
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
Interventions
BIOLOGICALVM202
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serious and Non Serious Adverse Events | Throughout the nine month follow up | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Screening, on Day 0 before the treatment (injection), on Day 30, Day 60, Day 90, at 6 months and 9 months | 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. |
| Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 0, Day 30, Day 60, Day 90, at 6 months and 9 months | 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. |
| Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 30, Day 60, Day 90, at 6 months and 9 months | pulmonary function test that quantifies the volume of air that can forcibly be blown out after full inspiration. It correlates with survival in ALS |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engensis (VM202) Group 1 Total dose of 64 mg of VM202, 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. Group 1 received Engensis IM injections beginning with the lower limbs, with injection location (lower vs upper limbs) alternating weekly
VM202 | 9 |
| Engensis (VM202) Group 2 Total dose of 64 mg of VM202, 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. Group 2 received Engensis IM injections beginning with the upper limbs, with injection location (lower vs upper limbs) alternating weekly
VM202 | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Engensis (VM202) Group 1 | Total | Engensis (VM202) Group 2 |
|---|---|---|---|
| Age, Continuous | 49.1 years STANDARD_DEVIATION 11.9 | 52.4 years STANDARD_DEVIATION 9.1 | 55.8 years STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 18 Participants | 9 Participants |
| Region of Enrollment United States | 9 participants | 18 participants | 9 participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 15 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 18 |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
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.
Time frame: Throughout the nine month follow up
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Diarrhoea | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Gastroesophargeal reflux disease | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Small intestinal obstruction | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Asthenia | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Fatigue | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Pyrexia | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Bronchitis | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Eye infection | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Lyme disease | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Nasopharyngitis | 4 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Tooth abscess | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Urinary tract infection | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Fall | 11 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Muscle strain | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Skin abrasion | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Skin laceration | 2 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Blood pressure increased | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Weight decreased | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Arthralgia | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Myalgia | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Headache | 3 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Depression | 2 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Haematuria | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Aspiration | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Cough | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Dyspnoea | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Pneumonia aspiration | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Respiratory failure | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Respiratory tract congestion | 1 Participants |
| Total | Number of Subjects With Serious and Non Serious Adverse Events | Rash | 1 Participants |
Secondary
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
Time frame: Day 30, Day 60, Day 90, at 6 months and 9 months
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 30 | -1.67 percentage | Standard Deviation 5.12 |
| Total | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 6 | -11.13 percentage | Standard Deviation 9.76 |
| Total | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 9 | -16.63 percentage | Standard Deviation 11.83 |
| Total | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 60 | -5 percentage | Standard Deviation 7.03 |
| Total | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 90 | -8 percentage | Standard Deviation 7.5 |
| Engensis (VM202) Group 2 | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 90 | -13.44 percentage | Standard Deviation 12.45 |
| Engensis (VM202) Group 2 | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 60 | -8.33 percentage | Standard Deviation 10.3 |
| Engensis (VM202) Group 2 | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 30 | -4.11 percentage | Standard Deviation 6.15 |
| Engensis (VM202) Group 2 | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 9 | -29.88 percentage | Standard Deviation 18.78 |
| Engensis (VM202) Group 2 | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 6 | -24 percentage | Standard Deviation 22.17 |
| Overall | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 9 | -23.25 percentage | Standard Deviation 16.64 |
| Overall | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Month 6 | -17.56 percentage | Standard Deviation 17.84 |
| Overall | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 30 | -2.89 percentage | Standard Deviation 5.63 |
| Overall | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 60 | -6.76 percentage | Standard Deviation 8.81 |
| Overall | Change From Baseline (Day 0) in Forced Vital Capacity (%) | Day 90 | -10.72 percentage | Standard Deviation 10.36 |
Secondary
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.
Time frame: Day 0, Day 30, Day 60, Day 90, at 6 months and 9 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 6 | -8.25 score on a scale | Standard Deviation 5.2 |
| Total | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 90 | -5.11 score on a scale | Standard Deviation 4.7 |
| Total | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 30 | -0.67 score on a scale | Standard Deviation 3.54 |
| Total | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 60 | -0.63 score on a scale | Standard Deviation 3.81 |
| Total | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 9 | -17.38 score on a scale | Standard Deviation 11.39 |
| Engensis (VM202) Group 2 | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 90 | -4.56 score on a scale | Standard Deviation 7.97 |
| Engensis (VM202) Group 2 | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 30 | -3.78 score on a scale | Standard Deviation 5.78 |
| Engensis (VM202) Group 2 | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 60 | -2.89 score on a scale | Standard Deviation 3.59 |
| Engensis (VM202) Group 2 | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 6 | -13.63 score on a scale | Standard Deviation 7.25 |
| Engensis (VM202) Group 2 | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 9 | -18.63 score on a scale | Standard Deviation 10.03 |
| Overall | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 9 | -18.0 score on a scale | Standard Deviation 10.39 |
| Overall | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Month 6 | -10.94 score on a scale | Standard Deviation 6.7 |
| Overall | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 30 | -2.22 score on a scale | Standard Deviation 4.92 |
| Overall | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 90 | -4.83 score on a scale | Standard Deviation 6.35 |
| Overall | Change in Mean Muscle Strength Medical Research Council (MRC) Scores | Day 60 | -1.82 score on a scale | Standard Deviation 3.76 |
Secondary
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.
Time frame: Screening, on Day 0 before the treatment (injection), on Day 30, Day 60, Day 90, at 6 months and 9 months
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 0 | 40.22 units on a scale | Standard Deviation 2.99 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 90 | 38.22 units on a scale | Standard Deviation 3.11 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 60 | 39.25 units on a scale | Standard Deviation 3.65 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Screening | 39.89 units on a scale | Standard Deviation 3.26 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 9 | 31.22 units on a scale | Standard Deviation 4.97 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 6 | 35.5 units on a scale | Standard Deviation 4.5 |
| Total | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 30 | 40 units on a scale | Standard Deviation 3.94 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 60 | 33.44 units on a scale | Standard Deviation 6.46 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Screening | 38.11 units on a scale | Standard Deviation 4.62 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 0 | 37.11 units on a scale | Standard Deviation 5.25 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 30 | 35 units on a scale | Standard Deviation 6.44 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 90 | 33.89 units on a scale | Standard Deviation 6.05 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 6 | 29.25 units on a scale | Standard Deviation 8.5 |
| Engensis (VM202) Group 2 | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 9 | 25.88 units on a scale | Standard Deviation 8.51 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 90 | 36.06 units on a scale | Standard Deviation 5.17 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 0 | 38.67 units on a scale | Standard Deviation 4.45 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 9 | 28.71 units on a scale | Standard Deviation 7.18 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Month 6 | 32.38 units on a scale | Standard Deviation 7.32 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 60 | 36.18 units on a scale | Standard Deviation 5.97 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Day 30 | 37.5 units on a scale | Standard Deviation 5.78 |
| Overall | The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) | Screening | 39 units on a scale | Standard Deviation 3.99 |