Safety of Engensis in Participants With Amyotrophic Lateral Sclerosis

Incidence of treatment-emergent adverse events in more than or equal to 10% of subjects, and treatment-emergent serious adverse events after injections, injection site reactions, and clinically significant laboratory values for Engensis compared to Placebo.

Time frame: From the Day 0 Visit to the Day 180 Visit

Population: Treatment-Emergent Adverse Events in ≥10% of Subjects Overall by System Organ Class and Preferred Term (Safety Analysis Population)

Change from Baseline (Day 0) in total mean Revised Amyotrophic Lateral Sclerosis Function Rating scores, subscores for Fine and Gross Motor Functions and Bulbar Function, and slope of the total score. The Revised Amyotrophic Lateral Sclerosis Function Rating scores 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. The Revised Amyotrophic Lateral Sclerosis Function Rating scores was conducted at Screening, pre-dose on Days 0, 60, and 120, and on Days 30, 84, 144, and 180.

Time frame: Day 0 to Day 180

Population: Revised Amyotrophic Lateral Sclerosis Function Rating scores - Change from Baseline to Day 180 (ITT Population)

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 from 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 84 and 180/ Early Termination.

Time frame: Day 84 to Day 180

Population: Clinical Global Impression of Change - ITT Population

As assessed bilaterally by the Accurate Test of Limb Isometric Strength where available. Accurate Test of Limb Isometric Strength - Muscle strength values for each muscle group and change from Baseline were presented, neither descriptive statistics presented by visit and treatment group.

Time frame: Day 0 to Day 180

Population: The Accurate Test of Limb Isometric Strength was not performed on any subject due to sites not being trained or were unable to conduct the procedure.

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 180 by Muscle Group (ITT Population)

Time frame: Day 0 to Day 180

Population: ITT Population

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 has made all the difference. The test was self-administered on Days 84 and 180.

Time frame: Day 84 and Day 180 (End of Study or Early Termination)

Population: Patient Global Impression of Change - ITT Population

The Amyotrophic Lateral Sclerosis Assessment Questionnaire has 40 items (ALSAQ-40), and is a standardized Quality of Life assessment. The Participant completes the 40 questions in the 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 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 is displayed in the Table. ALSAQ-40 was completed at the pre-dose visit (Day 0), and at the Day 84 and Day 180 visits. The Total Change From Baseline is calculated for the Day 84 visit, and the Day 180 visit.

Time frame: Day 0 to Day 84, and Day 0 to 180

Population: Amyotrophic Lateral Sclerosis Assessment Questionnaire. Percent Change from Baseline (ITT Population) for Engensis and Placebo.

Slow vital capacity is a pulmonary function test that quantifies the volume of air that can be slowly exhaled after slow maximum inhalation, and was to be measured at Screening, pre-dose on Days 60 and 120, and on Days 30, 84, 144, and 180.

Time frame: Day 0 to Day 180

Population: Slow Vital Capacity Percent Change from Baseline by Visit (ITT Population)

Total Participants that experienced Tracheostomy during the study in the Intent-to-treat population.

Time frame: Day 0 to Day 180

Population: Participants that Experienced Tracheostomy during the study - ITT Population

Participants that died during the study, for all causes including Treatment Emergent Adverse Events, or Treatment Emergent Serious Adverse Events, leading to study discontinuation, or study drug withdrawal in any subject.

Time frame: Day 0 to Day 180

Population: Time to All-Cause Death - ITT Population