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AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) (CENTAUR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03127514
Recruitment Status : Completed
First Posted : April 25, 2017
Results First Posted : August 11, 2021
Last Update Posted : August 11, 2021
Sponsor:
Collaborators:
ALS Finding a Cure
ALS Association
Northeast ALS Consortium
Neurological Clinical Research Institute at Massachusetts General Hospital
Leandro P. Rizzuto Foundation
Information provided by (Responsible Party):
Amylyx Pharmaceuticals Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Neuromuscular Diseases
Neurodegenerative Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Nervous System Diseases
Central Nervous System Diseases
Interventions Drug: AMX0035
Other: Placebo
Enrollment 137
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description

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 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

Period Title: Overall Study
Started 48 89
Completed 38 67
Not Completed 10 22
Arm/Group Title Placebo AMX0035 Total
Hide Arm/Group Description

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 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 of all reporting groups
Overall Number of Baseline Participants 48 87 135
Hide Baseline Analysis Population Description
Two participants in the AMX0035 group died soon after randomization and did not have a postbaseline efficacy assessment. These 2 participants were excluded from the primary efficacy analysis population (modified intention to treat (mITT) population), but were included in the safety population (intention to treat (ITT) population).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants 87 participants 135 participants
57.3  (7.6) 57.6  (10.4) 57.5  (9.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 87 participants 135 participants
Female
16
  33.3%
26
  29.9%
42
  31.1%
Male
32
  66.7%
61
  70.1%
93
  68.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 87 participants 135 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   2.1%
2
   2.3%
3
   2.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.1%
2
   2.3%
3
   2.2%
White
46
  95.8%
82
  94.3%
128
  94.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   1.1%
1
   0.7%
Time Since ALS Symptom Onset  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 48 participants 87 participants 135 participants
13.6  (3.6) 13.5  (3.8) 13.5  (3.8)
Bulbar Onset  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants 87 participants 135 participants
10
  20.8%
26
  29.9%
36
  26.7%
1.Primary Outcome
Title Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Slope Change
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 48 87
Least Squares Mean (Standard Error)
Unit of Measure: Change in ALSFRS-R Total Score Per Month
-1.66  (0.16) -1.24  (0.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, AMX0035
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments A two-tailed P value of 0.05 or less was considered to indicate statistical significance.
Method Mixed Models Analysis
Comments Random-slope, shared-baseline, linear mixed model was adjusted for age and prebaseline ALSFRS-R slope
2.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description Comparison Between Groups of Number of Participants With Adverse Events Until Planned Completion
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 48 89
Measure Type: Count of Participants
Unit of Measure: Participants
46
  95.8%
86
  96.6%
3.Primary Outcome
Title Number of Participants in Each Group Able to Remain on Study Drug Until Planned Discontinuation
Hide Description A comparison of the number of participants in each group able to remain on study drug until planned discontinuation between groups
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 48 87
Measure Type: Count of Participants
Unit of Measure: Participants
38
  79.2%
61
  70.1%
4.Secondary Outcome
Title Accurate Testing of Limb Isometric Strength (ATLIS) Total Score Change
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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)
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 47 84
Least Squares Mean (Standard Error)
Unit of Measure: % of Predicted Normal Change Per Month
-3.54  (0.26) -3.03  (0.19)
5.Secondary Outcome
Title Change in Plasma Levels of Phosphorylated Axonal Neurofilament H Subunit (pNF-H)
Hide Description 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
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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)
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 47 84
Least Squares Mean (Standard Error)
Unit of Measure: pg/ml Per Month
-2.34  (4.19) 3.58  (3.19)
6.Secondary Outcome
Title Rate of Decline in Slow Vital Capacity (SVC)
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 48 87
Least Squares Mean (Standard Error)
Unit of Measure: % of Predicted Normal Change Per Month
-4.03  (0.42) -3.10  (0.31)
7.Secondary Outcome
Title Death, Tracheostomy, and Hospitalization
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description:

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 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 Number of Participants Analyzed 48 87
Measure Type: Number
Unit of Measure: events
17 18
Time Frame Adverse event data were collected for the entire 24 week study
Adverse Event Reporting Description 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
 
Arm/Group Title Placebo AMX0035
Hide Arm/Group Description

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 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

All-Cause Mortality
Placebo AMX0035
Affected / at Risk (%) Affected / at Risk (%)
Total   2/48 (4.17%)   5/89 (5.62%) 
Hide Serious Adverse Events
Placebo AMX0035
Affected / at Risk (%) Affected / at Risk (%)
Total   9/48 (18.75%)   11/89 (12.36%) 
Eye disorders     
Vision blurred  1  0/48 (0.00%)  1/89 (1.12%) 
Gastrointestinal disorders     
Pneumoperitoneum  1  0/48 (0.00%)  1/89 (1.12%) 
Infections and infestations     
Bacteraemia  1  1/48 (2.08%)  1/89 (1.12%) 
Catheter Site Infection  1  1/48 (2.08%)  0/89 (0.00%) 
Cellulitis  1  0/48 (0.00%)  1/89 (1.12%) 
Diverticulitis  1  0/48 (0.00%)  1/89 (1.12%) 
Pneumonia  1  0/48 (0.00%)  1/89 (1.12%) 
Injury, poisoning and procedural complications     
Pelvic fracture  1  1/48 (2.08%)  0/89 (0.00%) 
Skull fracture  1  0/48 (0.00%)  1/89 (1.12%) 
Stoma site haemorrhage  1  0/48 (0.00%)  1/89 (1.12%) 
Subdural haematoma  1  0/48 (0.00%)  1/89 (1.12%) 
Product Issues     
Device dislocation  1  1/48 (2.08%)  0/89 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/48 (2.08%)  1/89 (1.12%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory failure  1  3/48 (6.25%)  2/89 (2.25%) 
Pulmonary Embolism  1  1/48 (2.08%)  0/89 (0.00%) 
Respiratory arrest  1  0/48 (0.00%)  1/89 (1.12%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo AMX0035
Affected / at Risk (%) Affected / at Risk (%)
Total   46/48 (95.83%)   86/89 (96.63%) 
Gastrointestinal disorders     
Diarrhoea  1  8/48 (16.67%)  19/89 (21.35%) 
Constipation  1  12/48 (25.00%)  12/89 (13.48%) 
Nausea  1  6/48 (12.50%)  16/89 (17.98%) 
Abdominal pain  1  4/48 (8.33%)  7/89 (7.87%) 
Salivary hypersecretion  1  1/48 (2.08%)  10/89 (11.24%) 
Dry mouth  1  4/48 (8.33%)  3/89 (3.37%) 
Abdominal pain upper  1  1/48 (2.08%)  4/89 (4.49%) 
Abdominal discomfort  1  0/48 (0.00%)  5/89 (5.62%) 
Dysphagia  1  4/48 (8.33%)  3/89 (3.37%) 
General disorders     
Fatigue  1  3/48 (6.25%)  7/89 (7.87%) 
Oedema peripheral  1  3/48 (6.25%)  2/89 (2.25%) 
Asthenia  1  0/48 (0.00%)  5/89 (5.62%) 
Infections and infestations     
Viral Upper Respiratory Tract Infection  1  2/48 (4.17%)  10/89 (11.24%) 
Urinary Tract Infection  1  3/48 (6.25%)  5/89 (5.62%) 
Upper Respiratory Tract Infection  1  3/48 (6.25%)  4/89 (4.49%) 
Injury, poisoning and procedural complications     
Fall  1  18/48 (37.50%)  25/89 (28.09%) 
Contusion  1  4/48 (8.33%)  5/89 (5.62%) 
Laceration  1  3/48 (6.25%)  6/89 (6.74%) 
Investigations     
Alanine aminotransferase increased  1  3/48 (6.25%)  4/89 (4.49%) 
Aspartate aminotransferase increased  1  3/48 (6.25%)  4/89 (4.49%) 
Weight decreased  1  1/48 (2.08%)  5/89 (5.62%) 
Metabolism and nutrition disorders     
Decreased appetite  1  2/48 (4.17%)  7/89 (7.87%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  9/48 (18.75%)  18/89 (20.22%) 
Back pain  1  4/48 (8.33%)  5/89 (5.62%) 
Muscle spasms  1  3/48 (6.25%)  5/89 (5.62%) 
Arthralgia  1  2/48 (4.17%)  5/89 (5.62%) 
Musculoskeletal pain  1  2/48 (4.17%)  5/89 (5.62%) 
Neck pain  1  5/48 (10.42%)  2/89 (2.25%) 
Musculoskeletal chest pain  1  1/48 (2.08%)  4/89 (4.49%) 
Nervous system disorders     
Headache  1  11/48 (22.92%)  13/89 (14.61%) 
Dizziness  1  2/48 (4.17%)  9/89 (10.11%) 
Psychiatric disorders     
Insomnia  1  3/48 (6.25%)  3/89 (3.37%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  4/48 (8.33%)  9/89 (10.11%) 
Cough  1  3/48 (6.25%)  5/89 (5.62%) 
Skin and subcutaneous tissue disorders     
Rash  1  4/48 (8.33%)  5/89 (5.62%) 
1
Term from vocabulary, MedDRA 16.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Amylyx Pharmaceuticals, Head of Clinical R&D
Organization: Amylyx Pharmaceuticals
Phone: (617) 682-0917
EMail: medinfo@amylyx.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Paganoni S, Hendrix S, Dickson SP, Knowlton N, Berry JD, Elliott MA, Maiser S, Karam C, Caress JB, Owegi MA, Quick A, Wymer J, Goutman SA, Heitzman D, Heiman-Patterson TD, Jackson C, Quinn C, Rothstein JD, Kasarskis EJ, Katz J, Jenkins L, Ladha SS, Miller TM, Scelsa SN, Vu TH, Fournier C, Johnson KM, Swenson A, Goyal N, Pattee GL, Babu S, Chase M, Dagostino D, Hall M, Kittle G, Eydinov M, Ostrow J, Pothier L, Randall R, Shefner JM, Sherman AV, Tustison E, Vigneswaran P, Yu H, Cohen J, Klee J, Tanzi R, Gilbert W, Yeramian P, Cudkowicz M. Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial. J Neurol Neurosurg Psychiatry. 2022 May 16. pii: jnnp-2022-329024. doi: 10.1136/jnnp-2022-329024. [Epub ahead of print]
Layout table for additonal information
Responsible Party: Amylyx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03127514    
Other Study ID Numbers: AMX-3500
First Submitted: April 12, 2017
First Posted: April 25, 2017
Results First Submitted: May 16, 2021
Results First Posted: August 11, 2021
Last Update Posted: August 11, 2021