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

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ClinicalTrials.gov Identifier: NCT03127514
Recruitment Status : Active, not recruiting
First Posted : April 25, 2017
Last Update Posted : October 10, 2019
Sponsor:
Collaborators:
ALS Finding a Cure Foundation
ALS Association
Northeast ALS Consortium
Massachusetts General Hospital Neurology Clinical Research Institute
Leandro P. Rizzuto Foundation
Information provided by (Responsible Party):
Amylyx Pharmaceuticals Inc.

Tracking Information
First Submitted Date  ICMJE April 12, 2017
First Posted Date  ICMJE April 25, 2017
Last Update Posted Date October 10, 2019
Actual Study Start Date  ICMJE June 22, 2017
Actual Primary Completion Date September 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • ALSFRS-R Slope [ Time Frame: 24 Weeks ]
    Change in slope of ALS Functional Rating Scale over treatment duration
  • Incidence of Adverse Events [ Time Frame: 24 Weeks ]
    Comparison Between Groups of Incidence of Adverse Events Until Planned Completion
  • Proportion of subjects in each group able to remain on study drug until planned discontinuation [ Time Frame: 24 weeks ]
    A comparison of the proportion of subjects in each group able to remain on study drug until planned discontinuation between groups
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03127514 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2017)
  • Accurate Testing of Limb Isometric Strength (ATLIS) [ Time Frame: 24 Weeks ]
    Change in rate of decline of isometric muscle strength over treatment duration
  • Blood-based Biomarkers [ Time Frame: 24 Weeks ]
    Change in levels of plasma-based biomarkers of neuronal death and axonal integrity from baseline to week 24
  • Slow Vital Capacity [ Time Frame: 24 Weeks ]
    Change in slope of slow vital capacity decline over treatment duration
  • Survival, tracheostomy and hospitalizations [ Time Frame: 24 Weeks ]
    Comparison of rate of occurrence between groups
  • Imaging Biomarkers [ Time Frame: 24 Weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE Evaluation of the Safety, Tolerability, Efficacy and Activity of AMX0035, a Fixed Combination of Phenylbutyrate (PB) and Tauroursodeoxycholic Acid (TUDCA), for the Treatment of ALS
Brief Summary The CENTAUR trial will be a 2:1 (active:placebo) randomized, double-blind, placebo-controlled Phase II trial to evaluate the safety and efficacy of AMX0035 for the treatment of ALS.
Detailed Description AMX0035 is a combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). This clinical trial is designed to demonstrate that treatment is safe, tolerable, and able to slow decline in function as measured by the ALSFRS-R. The trial will also assess the effects of AMX0035 on muscle strength, vital capacity, and biomarkers of ALS including markers of neuronal death and neuroinflammation.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Amyotrophic Lateral Sclerosis
  • Motor Neuron Disease
  • Neuromuscular Diseases
  • Neurodegenerative Diseases
  • Spinal Cord Diseases
  • TDP-43 Proteinopathies
  • Nervous System Diseases
  • Central Nervous System Diseases
Intervention  ICMJE
  • Drug: AMX0035
    AMX0035
    Other Name: Tauroursodeoxycholic Acid and Sodium Phenylbutyrate
  • Other: Placebo
    Matching Placebo Comparator
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo administered twice daily p.o. for 24 weeks
    Intervention: Other: Placebo
  • Experimental: AMX0035
    AMX0035 administered twice daily p.o. for 24 weeks
    Intervention: Drug: AMX0035
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2017)
132
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2019
Actual Primary Completion Date September 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Male or female, aged 18-80 years of age
  2. Sporadic or familial ALS diagnosed as definite as defined by the World Federation of Neurology revised El Escorial criteria
  3. Less than or equal to 18 months since ALS symptom onset
  4. Capable of providing informed consent and following trial procedures
  5. Slow Vital Capacity (SVC) >60% of predicted value for gender, height, and age at the Screening Visit
  6. Subjects must either not take riluzole or be on a stable dose of riluzole for at least 30 days prior to the Screening Visit. Riluzole-naïve subjects are permitted in the study.
  7. Women of child bearing potential (e.g. not post-menopausal for at least one year or surgically sterile) must agree to use adequate birth control for the duration of the study and 3 months after last dose of study drug. Women must not be planning to become pregnant for the duration of the study and 3 months after last dose of study drug
  8. Men must agree to practice contraception for the duration of the study and 3 months after last dose of study drug. Men must not plan to father a child or provide for sperm donation for the duration of the study and 3 months after last dose of study drug

Key Exclusion Criteria:

  1. Presence of tracheostomy
  2. Exposure to PB, TUDCA or UDCA within 3 months prior to the Screening Visit or planning to use these medications during the course of the study
  3. History of known allergy to PB or bile salts
  4. Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal
  5. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal
  6. Poorly controlled arterial hypertension (SBP>160mmHg or DBP>100mmHg) at the Screening Visit
  7. Pregnant women or women currently breastfeeding
  8. History of cholecystectomy
  9. Biliary disease which impedes biliary flow including active cholecystitis, primary biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gallbladder polyps, gangrene of the gallbladder, abscess of the gallbladder.
  10. History of Class III/IV heart failure (per New York Heart Association - NYHA)
  11. Severe pancreatic or intestinal disorders that may alter the enterohepatic circulation and absorption of TUDCA including biliary infections, pancreatitis and ileal resection
  12. The presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the subject to provide informed consent, according to Site Investigator judgment
  13. Clinically significant unstable medical condition (other than ALS) that would pose a risk to the subject if they were to participate in the study
  14. Active participation in an ALS clinical trial evaluating a small molecule within 30 days of the Screening Visit
  15. Exposure at any time to any biologic under investigation for the treatment of subjects with ALS (off-label use or investigational) including cell therapies, gene therapies, and monoclonal antibodies.
  16. Implantation of Diaphragm Pacing System (DPS)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03127514
Other Study ID Numbers  ICMJE AMX-3500
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Amylyx Pharmaceuticals Inc.
Study Sponsor  ICMJE Amylyx Pharmaceuticals Inc.
Collaborators  ICMJE
  • ALS Finding a Cure Foundation
  • ALS Association
  • Northeast ALS Consortium
  • Massachusetts General Hospital Neurology Clinical Research Institute
  • Leandro P. Rizzuto Foundation
Investigators  ICMJE
Study Director: Patrick Yeramian, MD Amylyx Pharmaceuticals Inc.
Principal Investigator: Sabrina Paganoni, MD Massachusetts General Hospital
PRS Account Amylyx Pharmaceuticals Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP