Trial Outcomes & Findings for AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT03127514)

Last Updated: 2024-05-16

Results Overview

Change in slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over treatment duration. The ALSFRS-R consists of 12 items across 4 subdomains of function (bulbar, fine motor, gross motor, and breathing) with each item scored on a scale from 0 (total loss of function) to 4 (no loss of function). Total scores range from 0 to 48, with higher scores indicating better function.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

24 Weeks

Results posted on

2024-05-16

Participant Flow

Adults with sporadic or familial ALS were enrolled at 25 centers of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) in the United States from June 2017 through September 2019.

Participant milestones

Participant milestones
Measure	Placebo Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Overall Study STARTED	48	89
Overall Study COMPLETED	38	67
Overall Study NOT COMPLETED	10	22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=87 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035	Total n=135 Participants Total of all reporting groups
Age, Continuous	57.3 years STANDARD_DEVIATION 7.6 • n=5 Participants	57.6 years STANDARD_DEVIATION 10.4 • n=7 Participants	57.5 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	26 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	61 Participants n=7 Participants	93 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	82 Participants n=7 Participants	128 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Time Since ALS Symptom Onset	13.6 months STANDARD_DEVIATION 3.6 • n=5 Participants	13.5 months STANDARD_DEVIATION 3.8 • n=7 Participants	13.5 months STANDARD_DEVIATION 3.8 • n=5 Participants
Bulbar Onset	10 Participants n=5 Participants	26 Participants n=7 Participants	36 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: mITT population

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=87 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change	-1.66 Change in ALSFRS-R Total Score Per Month Standard Error 0.16	-1.24 Change in ALSFRS-R Total Score Per Month Standard Error 0.12

PRIMARY outcome

Timeframe: 24 Weeks

Population: ITT population

Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=89 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Number of Participants With Adverse Events	46 Participants	86 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: mITT population

A comparison of the number of participants in each group able to remain on study drug until planned discontinuation between groups

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=87 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation	38 Participants	61 Participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: mITT population (1 participant in the placebo group and 3 in the AMX0035 group did not have complete muscle strength data and are not included in this analysis population)

The ATLIS device assess the isometric muscle strength of six upper-limb and six lower-limb muscle groups. At least two trials are performed for each muscle group to assess change in rate of decline of isometric muscle strength over treatment duration. Values are standardized to the percentage of predicted normal strength based on sex, age, weight, and height. Results are presented as percent of predicted normal.

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=84 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Accurate Testing of Limb Isometric Strength (ATLIS) Total Score Change	-3.54 % of Predicted Normal Change Per Month Standard Error 0.26	-3.03 % of Predicted Normal Change Per Month Standard Error 0.19

SECONDARY outcome

Timeframe: 24 Weeks

Population: mITT population (1 participant in the placebo group and 3 in the AMX0035 group did not have sample analyzed and are not included in this analysis population)

Neuronal degeneration releases phosphorylated axonal neurofilament H subunit (pNF-H) into the cerebrospinal fluid and subsequently the blood and is thought to be a potential biomarker of motor neuron degeneration; elevated plasma levels of pNF-H are presumed to correlate with neuronal injury. Change in levels of plasma pNF-H were measured from baseline to week 24

Outcome measures

Outcome measures
Measure	Placebo n=47 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=84 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Change in Plasma Levels of Phosphorylated Axonal Neurofilament H Subunit (pNF-H)	-2.34 pg/ml Per Month Standard Error 4.19	3.58 pg/ml Per Month Standard Error 3.19

SECONDARY outcome

Timeframe: 24 Weeks

Population: mITT population

Respiratory muscle function was assessed according to slow vital capacity (SVC). SVC was measured in an upright position for at least three trials per assessment. SVC volumes were standardized to the percentage of predicted normal value based on age, sex, and height.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=87 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Rate of Decline in Slow Vital Capacity (SVC)	-4.03 % of Predicted Normal Change Per Month Standard Error 0.42	-3.10 % of Predicted Normal Change Per Month Standard Error 0.31

SECONDARY outcome

Timeframe: 24 Weeks

Population: mITT population

The composite outcome was defined as death, a death-equivalent event (which consisted of only tracheostomy in one participant in this trial), or hospitalization, whichever occurred first; there were no instances of permanent ventilation delivered by noninvasive means in the study.

Outcome measures

Outcome measures
Measure	Placebo n=48 Participants Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=87 Participants AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Death, Tracheostomy, and Hospitalization	17 events	18 events

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 46 other events

Deaths: 2 deaths

AMX0035

Serious events: 11 serious events

Other events: 86 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Amylyx Pharmaceuticals, Head of Clinical R&D

Amylyx Pharmaceuticals

Phone: (617) 682-0917

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=48 participants at risk Placebo administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating Placebo: Matching Placebo Comparator	AMX0035 n=89 participants at risk AMX0035 administered by mouth or via feeding tube for 24 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating AMX0035: AMX0035
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.2% 3/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	2.2% 2/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	0.00% 0/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Infections and infestations Bacteraemia	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Infections and infestations Catheter Site Infection	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	0.00% 0/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Infections and infestations Cellulitis	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Infections and infestations Diverticulitis	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Infections and infestations Pneumonia	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Injury, poisoning and procedural complications Pelvic fracture	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	0.00% 0/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Injury, poisoning and procedural complications Skull fracture	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Injury, poisoning and procedural complications Stoma site haemorrhage	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Gastrointestinal disorders Pneumoperitoneum	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Renal and urinary disorders Nephrolithiasis	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Eye disorders Vision blurred	0.00% 0/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	1.1% 1/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event
Product Issues Device dislocation	2.1% 1/48 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event	0.00% 0/89 • Adverse event data were collected for the entire 24 week study Symptoms of ALS progression, including those consistent with disease progression were recorded as adverse events. Any worsening of a disease progression measure that was being analyzed separately (ALSFRS-R, ATLIS, and SVC) was not recorded as an adverse event