Amyotrophic Lateral Sclerosis
Conditions
Brief summary
The purpose of this study is to evaluate the long-term safety of intramuscular administration of Engensis in Participants with Amyotrophic Lateral Sclerosis who were previously randomized, received treatment, and completed the Day 180 Visit of Study VMALS-002-2. Safety will be assessed by incidences of treatment-emergent adverse events, treatment emergent serious adverse events, adverse events of special interest, and the clinically significant laboratory values.
Detailed description
VMALS-002-2b was a safety extension study following VMALS-002-2, which was a Phase 2a, double-blind, randomized, placebo-controlled, multicenter study designed to assess the safety of intramuscular administration of Engensis in subjects with Amyotrophic Lateral Sclerosis.Following completion of the Day 180 visit in VMALS-002-2 and signing of written informed consent, subjects were enrolled in this approximately 180-day extension study, with subjects completing combined participation with a Day 365 visit. Assessments to be conducted during this extension study were as follows: vital signs, weight and height, complete physical examination, 12-lead electrocardiogram, a record of all concomitant medications and procedures, clinical laboratory assessments, Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, handheld dynamometry, slow vital capacity, Amyotrophic Lateral Sclerosis Assessment Questionnaire, 40 questions, Patient Global Impression of Change, and Clinical Global Impression of Change. Assessments of treatment-emergent adverse events, treatment-emergent serious adverse events, adverse events of special interest, and clinically significant laboratory values continued from the Day 180 visit of Study VMALS-002-2 through the VMALS-002-2b extension study to Day 365.
Interventions
BIOLOGICALEngensis
Lyophilized biologic to be reconstituted containing Engensis
OTHERPlacebo
Injectable Liquid
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants who complete the Day 180 Visit in VMALS-002-2 are eligible to enroll in this extension study, VMALS-002-2b.
Exclusion criteria
\- None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Day 0 to Day 365 | To evaluate the long-term safety of intramuscular injections of Engensis in Participants with Amyotrophic Lateral Sclerosis in more than 2 Participants by System Organ Class and Preferred Term (Safety Analysis Population) |
Other
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Day 0 and Day 365 | As assessed bilaterally by Hand-Held Dynamometry in muscles in the upper and lower extremities. Muscle Strength as Measured by Handheld Dynamometry (lbs.) and Change from Baseline to Day 365 by Muscle Group (ITT Population) |
| To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 0, Day 240, Day 300 and Day 365 | Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation. It is measured in Liters of air and the percentage of change from baseline is the Percent Predicted Value and Change from Baseline. Change from Baseline (Study VMALS 002-2, Day 0) in Slow Vital Capacity on Day 240, Day 300 and Day 365 for Participants with intramuscular administration of Engensis compared to Placebo. Increasing negative Change from Baseline results indicates worsening of respiratory capacity. |
| To Determine if Intramuscular Engensis Has Effects on Respiratory Function in Amyotrophic Lateral Sclerosis Participants - Tracheostomy | Day 0 to Day 365 | Total participants requiring Tracheostomy procedures that received intramuscular administration of Engensis, compared to total Placebo participants requiring Tracheostomy procedures. |
| To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Day 0 and Day 365 | Changes from Baseline (Study VMALS 002-2, Day 0) in Revised Amyotrophic Lateral Sclerosis Function Rating TOTAL scores at Day 365 for Engensis compared to Placebo There are 12 separate assessments in this neuromuscular assessment covering Bulbar, Fine Motor, Gross Motor and Breathing assessments. Each individual assessment is scored from 0 (worst case) to 4 (best case). Total score is calculated as the sum of all 12 assessment subscores. Note that only the Total Score will be reported in the clinical study report due to the small number of subjects. The Total Score range is from a minimum of 0 (worst case) to a maximum of 48 (best case). |
| To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 0, Day 240 and Day 365 | The Participant completes the 40 questions in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with 5 categories: Physical Mobility, Activities of Daily Living and Independence, Eating and Drinking, Communication, and Emotional Reactions. Each question has 5 responses to select from: 0-Never (Best Case), 1-Rarely, 2-Sometime, 3-Often, and 4-Always (Worst Case). Note for each question there is a Minimum of 0 (Best), to the Maximum 4 (Worst). Decreasing scores indicates improvement of symptoms. The Total Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) scores are per Category as percentages of 100% maximum. Each Category percentage is summed for the Intent-to-treat Population. The Change from Baseline was calculated and displayed in the Table. ALSAQ-40 was completed at the pre-dose baseline visit (Day 0), and at the Day 240 and Day 365 visits. |
| To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 and Day 365 | The subject's impression of change after treatment was measured with the Patient Global Impression of Change questionnaire through use of the electronic Patient Reported Outcome . This questionnaire measures the subject's perception of how treatment has affected their level of activity, symptoms, emotions, and overall quality of life. Each descriptor is ranked on an increasing improvement scale; where 1 = No change (or condition has got worse), 2=Almost the same, hardly any change at all, 3=A little better, but no noticeable change, 4=Somewhat better, but the change has not made any real difference, 5=Moderately better, and a slight but noticeable change, 6=Better, and a definite improvement that has made a real and worthwhile difference, and 7 = A great deal better, and a considerable improvement that as made all the difference. The test was self-administered on Days 240 and 365. |
| To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 and Day 365 | The Clinical Global Impression of Change is a validated instrument completed by observers as an assessment of Quality of Life. The Clinical Global Impression of Change is an 8-point scale with scores ranging rom Marked Improvement, Moderate Improvement, Minimal Improvement, Slight Improvement, and Unchanged (or Worse), along with an efficacy index with questions in a matrix for therapeutic effect and side effects.The test was completed on Days 240 and 365/ Early Termination. |
| To Determine if Intramuscular Administration of Engensis Has Positive Effects on Survival in Amyotrophic Lateral Sclerosis Participants - All-Cause Mortality | Day 0 to Day 365 | Total all-cause Mortality for participants that received intramuscular injections of Engensis, compared to total all-cause Mortality for Placebo participants. Total participant deaths that received intramuscular administration of Engensis, compared to total Placebo participant deaths. |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engensis Active Comparator: Engensis 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
Engensis: Lyophilized biologic to be reconstituted containing Engensis | 4 |
| Placebo Placebo Comparator: Placebo 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
Placebo: Injectable Liquid | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Engensis | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Continuous | 39.0 years STANDARD_DEVIATION 16.99 | 52.3 years STANDARD_DEVIATION 10.63 | 45.6 years STANDARD_DEVIATION 14.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 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 | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment South Korea | 3 participants | 2 participants | 5 participants |
| Region of Enrollment United States | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 | 1 / 4 |
Outcome results
Primary
Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term
To evaluate the long-term safety of intramuscular injections of Engensis in Participants with Amyotrophic Lateral Sclerosis in more than 2 Participants by System Organ Class and Preferred Term (Safety Analysis Population)
Time frame: Day 0 to Day 365
Population: Percentages were based on the number of subjects in the Safety Analysis Population by treatment group and overall.~Subjects were counted once within for each unique Preferred Term.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Injection site pain | 1 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Dysphagia | 3 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Pyrexia | 2 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Arthralgia | 1 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Cough | 3 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Myalgia | 1 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Asthenia | 0 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | COVID-19 | 3 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Rhinorrhoea | 1 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Headache | 1 Participants |
| Engensis | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Injection site bruising | 3 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Headache | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Injection site bruising | 3 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Asthenia | 2 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Pyrexia | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Injection site pain | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Cough | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Rhinorrhoea | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Dysphagia | 2 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Arthralgia | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | Myalgia | 1 Participants |
| Placebo | Treatment-Emergent Adverse Events in More Than 2 Subjects Overall by System Organ Class and Preferred Term | COVID-19 | 2 Participants |
Other Pre-specified
To Determine if Intramuscular Administration of Engensis Has Positive Effects on Survival in Amyotrophic Lateral Sclerosis Participants - All-Cause Mortality
Total all-cause Mortality for participants that received intramuscular injections of Engensis, compared to total all-cause Mortality for Placebo participants. Total participant deaths that received intramuscular administration of Engensis, compared to total Placebo participant deaths.
Time frame: Day 0 to Day 365
Population: Total all-cause Mortality for participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engensis | To Determine if Intramuscular Administration of Engensis Has Positive Effects on Survival in Amyotrophic Lateral Sclerosis Participants - All-Cause Mortality | 0 Participants |
| Placebo | To Determine if Intramuscular Administration of Engensis Has Positive Effects on Survival in Amyotrophic Lateral Sclerosis Participants - All-Cause Mortality | 0 Participants |
Other Pre-specified
To Determine if Intramuscular Engensis Has Effects on Respiratory Function in Amyotrophic Lateral Sclerosis Participants - Tracheostomy
Total participants requiring Tracheostomy procedures that received intramuscular administration of Engensis, compared to total Placebo participants requiring Tracheostomy procedures.
Time frame: Day 0 to Day 365
Population: Total Tracheostomy procedures for the Safety Analysis Population - Number of Participants - Day 0 to Day 365
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engensis | To Determine if Intramuscular Engensis Has Effects on Respiratory Function in Amyotrophic Lateral Sclerosis Participants - Tracheostomy | 0 Participants |
| Placebo | To Determine if Intramuscular Engensis Has Effects on Respiratory Function in Amyotrophic Lateral Sclerosis Participants - Tracheostomy | 0 Participants |
Other Pre-specified
To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants
Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation. It is measured in Liters of air and the percentage of change from baseline is the Percent Predicted Value and Change from Baseline. Change from Baseline (Study VMALS 002-2, Day 0) in Slow Vital Capacity on Day 240, Day 300 and Day 365 for Participants with intramuscular administration of Engensis compared to Placebo. Increasing negative Change from Baseline results indicates worsening of respiratory capacity.
Time frame: Day 0, Day 240, Day 300 and Day 365
Population: Slow Vital Capacity Percent Change from Baseline by Visit (ITT Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 240 - Change from Baseline | 0.0 percentage of Change from Baseline | Standard Deviation 1.41 |
| Engensis | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 300 - Change from Baseline | -9.3 percentage of Change from Baseline | Standard Deviation 11.9 |
| Engensis | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 365/Early Term - Change from Baseline | -17.3 percentage of Change from Baseline | Standard Deviation 19.39 |
| Placebo | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 240 - Change from Baseline | -16.5 percentage of Change from Baseline | Standard Deviation 7.78 |
| Placebo | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 300 - Change from Baseline | -7.3 percentage of Change from Baseline | Standard Deviation 19.33 |
| Placebo | To Determine Whether Intramuscular Administration of Engensis Has Effects on Respiratory Capacity in Amyotrophic Lateral Sclerosis Participants | Day 365/Early Term - Change from Baseline | -15.0 percentage of Change from Baseline | Standard Deviation 17.52 |
Other Pre-specified
To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants
Changes from Baseline (Study VMALS 002-2, Day 0) in Revised Amyotrophic Lateral Sclerosis Function Rating TOTAL scores at Day 365 for Engensis compared to Placebo There are 12 separate assessments in this neuromuscular assessment covering Bulbar, Fine Motor, Gross Motor and Breathing assessments. Each individual assessment is scored from 0 (worst case) to 4 (best case). Total score is calculated as the sum of all 12 assessment subscores. Note that only the Total Score will be reported in the clinical study report due to the small number of subjects. The Total Score range is from a minimum of 0 (worst case) to a maximum of 48 (best case).
Time frame: Day 0 and Day 365
Population: Revised Amyotrophic Lateral Sclerosis Function Rating Total Score and Change from Baseline to Day 365 (Safety Analysis Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Baseline - actual value | 39.0 score on a scale | Standard Deviation 1.41 |
| Engensis | To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Day 365 / Early Termination - change from baseline | -10.5 score on a scale | Standard Deviation 8.23 |
| Placebo | To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Baseline - actual value | 30.8 score on a scale | Standard Deviation 5.62 |
| Placebo | To Evaluate Changes in Muscle Function Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Day 365 / Early Termination - change from baseline | -8.7 score on a scale | Standard Deviation 9.61 |
Other Pre-specified
To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo
The Clinical Global Impression of Change is a validated instrument completed by observers as an assessment of Quality of Life. The Clinical Global Impression of Change is an 8-point scale with scores ranging rom Marked Improvement, Moderate Improvement, Minimal Improvement, Slight Improvement, and Unchanged (or Worse), along with an efficacy index with questions in a matrix for therapeutic effect and side effects.The test was completed on Days 240 and 365/ Early Termination.
Time frame: Day 240 and Day 365
Population: Clinical Global Impression of Change - ITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Much worse | 0 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination - No change | 2 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Minimally worse | 1 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination Minimally worse | 0 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination - Minimally improved | 0 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination Much worse | 2 Participants |
| Engensis | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - No change | 2 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination Much worse | 1 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - No change | 1 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Minimally worse | 1 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Much worse | 1 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination - Minimally improved | 1 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination - No change | 0 Participants |
| Placebo | To Evaluate Clinician Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365 / Early Termination Minimally worse | 1 Participants |
Other Pre-specified
To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants
As assessed bilaterally by Hand-Held Dynamometry in muscles in the upper and lower extremities. Muscle Strength as Measured by Handheld Dynamometry (lbs.) and Change from Baseline to Day 365 by Muscle Group (ITT Population)
Time frame: Day 0 and Day 365
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Left - Baseline - Actual | 24.10 Pounds | Standard Deviation 12.572 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion-Left - Day 365 - Change from Baseline | -20.190 Pounds | Standard Deviation 15.8662 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion- Right - Baseline - Actual | 30.53 Pounds | Standard Deviation 26.522 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion-Right - Day 365 - Change from Baseline | -20.45 Pounds | Standard Deviation 16.083 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Left - Day 365 - Change from Baseline | -16.13 Pounds | Standard Deviation 12.419 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion- Right - Baseline - Actual | 24.645 Pounds | Standard Deviation 11.5448 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Right - Day 365 - Change from Baseline | -16.395 Pounds | Standard Deviation 12.8508 |
| Engensis | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion- Left - Baseline - Actual | 29.440 Pounds | Standard Deviation 25.1779 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Left - Baseline - Actual | 20.08 Pounds | Standard Deviation 11.538 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion- Left - Baseline - Actual | 14.525 Pounds | Standard Deviation 10.1923 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion- Right - Baseline - Actual | 17.850 Pounds | Standard Deviation 12.0423 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion-Left - Day 365 - Change from Baseline | -5.433 Pounds | Standard Deviation 3.6501 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Left - Day 365 - Change from Baseline | -8.40 Pounds | Standard Deviation 5.173 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion- Right - Baseline - Actual | 13.73 Pounds | Standard Deviation 11.667 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Shoulder Flexion-Right - Day 365 - Change from Baseline | -5.900 Pounds | Standard Deviation 5.1798 |
| Placebo | To Evaluate Muscle Strength Changes Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants | Elbow Flexion-Right - Day 365 - Change from Baseline | -4.1 Pounds | Standard Deviation 1.082 |
Other Pre-specified
To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo
The subject's impression of change after treatment was measured with the Patient Global Impression of Change questionnaire through use of the electronic Patient Reported Outcome . This questionnaire measures the subject's perception of how treatment has affected their level of activity, symptoms, emotions, and overall quality of life. Each descriptor is ranked on an increasing improvement scale; where 1 = No change (or condition has got worse), 2=Almost the same, hardly any change at all, 3=A little better, but no noticeable change, 4=Somewhat better, but the change has not made any real difference, 5=Moderately better, and a slight but noticeable change, 6=Better, and a definite improvement that has made a real and worthwhile difference, and 7 = A great deal better, and a considerable improvement that as made all the difference. The test was self-administered on Days 240 and 365.
Time frame: Day 240 and Day 365
Population: Patient Global Impression of Change - ITT Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engensis | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Impression change - or worse | 2 Participants |
| Engensis | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Impression change - Almost the same, hardly any change | 1 Participants |
| Engensis | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early termination - Impression change - or worse | 4 Participants |
| Engensis | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Impression change - Almost the same, hardly any change | 0 Participants |
| Placebo | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Impression change - Almost the same, hardly any change | 1 Participants |
| Placebo | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early termination - Impression change - or worse | 2 Participants |
| Placebo | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Impression change - or worse | 2 Participants |
| Placebo | To Evaluate Patient Reported Outcome Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Impression change - Almost the same, hardly any change | 1 Participants |
Other Pre-specified
To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo
The Participant completes the 40 questions in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) with 5 categories: Physical Mobility, Activities of Daily Living and Independence, Eating and Drinking, Communication, and Emotional Reactions. Each question has 5 responses to select from: 0-Never (Best Case), 1-Rarely, 2-Sometime, 3-Often, and 4-Always (Worst Case). Note for each question there is a Minimum of 0 (Best), to the Maximum 4 (Worst). Decreasing scores indicates improvement of symptoms. The Total Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) scores are per Category as percentages of 100% maximum. Each Category percentage is summed for the Intent-to-treat Population. The Change from Baseline was calculated and displayed in the Table. ALSAQ-40 was completed at the pre-dose baseline visit (Day 0), and at the Day 240 and Day 365 visits.
Time frame: Day 0, Day 240 and Day 365
Population: Percent Change from Baseline (ITT Population) for Engensis and Placebo.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Communication | 26.80 percentage of Change from Baseline | Standard Deviation 33.35 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Eating and Drinking | 0 percentage of Change from Baseline | Standard Deviation 0 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Physical mobility | 13.75 percentage of Change from Baseline | Standard Deviation 9.465 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Eating and Drinking | 20.83 percentage of Change from Baseline | Standard Deviation 24.994 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Communication | 16.67 percentage of Change from Baseline | Standard Deviation 32.036 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Emotional Functioning | 3.33 percentage of Change from Baseline | Standard Deviation 13.769 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Activities of Daily Living/Independence | 14.17 percentage of Change from Baseline | Standard Deviation 11.815 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Physical mobility | 12.5 percentage of Change from Baseline | Standard Deviation 2.5 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Emotional Functioning | 10.00 percentage of Change from Baseline | Standard Deviation 24.833 |
| Engensis | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Activities of Daily Living/Independence | 21.88 percentage of Change from Baseline | Standard Deviation 21.25 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Emotional Functioning | 12.50 percentage of Change from Baseline | Standard Deviation 4.33 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Physical mobility | 3.33 percentage of Change from Baseline | Standard Deviation 20.817 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Physical mobility | 21.67 percentage of Change from Baseline | Standard Deviation 24.664 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Activities of Daily Living/Independence | -.83 percentage of Change from Baseline | Standard Deviation 3.819 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Activities of Daily Living/Independence | 10.00 percentage of Change from Baseline | Standard Deviation 8.66 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Eating and Drinking | 11.13 percentage of Change from Baseline | Standard Deviation 25.411 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Communication | 28.57 percentage of Change from Baseline | Standard Deviation 6.207 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Communication | 32.17 percentage of Change from Baseline | Standard Deviation 35.7 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 240 - Emotional Functioning | 7.50 percentage of Change from Baseline | Standard Deviation 18.875 |
| Placebo | To Evaluate Quality of Life Improvement Following Engensis Injections in Amyotrophic Lateral Sclerosis Participants Compared to Placebo | Day 365/Early Termination - Eating and Drinking | 33.33 percentage of Change from Baseline | Standard Deviation 28.868 |