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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 : March 5, 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.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Motor Neuron Disease Neuromuscular Diseases Neurodegenerative Diseases Spinal Cord Diseases TDP-43 Proteinopathies Nervous System Diseases Central Nervous System Diseases Drug: AMX0035 Other: Placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 22, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo administered twice daily p.o. for 24 weeks
 Other: Placebo
Matching Placebo Comparator
Experimental: AMX0035
AMX0035 administered twice daily p.o. for 24 weeks
 Drug: AMX0035
AMX0035
Other Name: Tauroursodeoxycholic Acid and Sodium Phenylbutyrate


Outcome Measures
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Primary Outcome Measures :
  1. ALSFRS-R Slope [ Time Frame: 24 Weeks ]
    Change in slope of ALS Functional Rating Scale over treatment duration

  2. Incidence of Adverse Events [ Time Frame: 24 Weeks ]
    Comparison Between Groups of Incidence of Adverse Events Until Planned Completion

  3. 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


Secondary Outcome Measures :
  1. Accurate Testing of Limb Isometric Strength (ATLIS) [ Time Frame: 24 Weeks ]
    Change in rate of decline of isometric muscle strength over treatment duration

  2. 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

  3. Slow Vital Capacity [ Time Frame: 24 Weeks ]
    Change in slope of slow vital capacity decline over treatment duration

  4. Survival, tracheostomy and hospitalizations [ Time Frame: 24 Weeks ]
    Comparison of rate of occurrence between groups

  5. Imaging Biomarkers [ Time Frame: 24 Weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03127514


  Show 25 Study Locations
Sponsors and Collaborators
Amylyx Pharmaceuticals Inc.
ALS Finding a Cure Foundation
ALS Association
Northeast ALS Consortium
Massachusetts General Hospital Neurology Clinical Research Institute
Leandro P. Rizzuto Foundation
Investigators
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Study Director: Patrick Yeramian, MD Amylyx Pharmaceuticals Inc.
Principal Investigator: Sabrina Paganoni, MD Massachusetts General Hospital
More Information
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Additional Information:
TUDCA in patients with ALS  This link exits the ClinicalTrials.gov site Phenylbutyrate in patients with ALS  This link exits the ClinicalTrials.gov site

Publications:

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Responsible Party: Amylyx Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03127514     History of Changes
Other Study ID Numbers: AMX-3500
First Posted: April 25, 2017    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amylyx Pharmaceuticals Inc.:
Randomized
Double-blind
Placebo-controlled
 Amyotrophic Lateral Sclerosis
Sodium Phenylbutyrate
Tauroursodeoxycholic Acid

Additional relevant MeSH terms:
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Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Nervous System Diseases
Neuromuscular Diseases
Neurodegenerative Diseases
Central Nervous System Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Pathologic Processes
 Proteostasis Deficiencies
Metabolic Diseases
4-phenylbutyric acid
Tauroursodeoxycholic acid
Taurochenodeoxycholic Acid
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Cholagogues and Choleretics
Gastrointestinal Agents