AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Condition: Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Nervous System Diseases; Central Nervous System Diseases
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Diseases; Central Nervous System Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Sclerosis
Intervention: AMX0035; Placebo
Intervention description: AMX0035; Matching Placebo Comparator
Intervention MeSH terms: 4-phenylbutyric acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Randomized; Double-blind; Placebo-controlled; Amyotrophic Lateral Sclerosis; Sodium Phenylbutyrate; Tauroursodeoxycholic Acid

Summary:

      The CENTAUR trial was 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.
    

Eligibility 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, Taurursodiol 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 aspartate aminotransferase (AST) and/or alanine
             aminotransferase (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 (systolic blood pressure (SBP)>160mmHg or
             diastolic blood pressure (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)