The Phoenix Trial is a randomized double blind placebo controlled Phase III trial to evaluate the safety and efficacy of AMX0035 for treatment of ALS
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 and survival over 48 week. The trial will also assess the effects of AMX0035 on slow vital capacity, quality of life and plasma biomarkers of ALS.
Inclusion Criteria:
- Male or female, at least 18 years of age
- Diagnosis of ALS (definite or clinically probable)
- Time since onset of first symptom of ALS should be <24 months prior to
randomization;
- If the participant is to be treated with riluzole and/or edaravone during the course
of the trial, then treatment with riluzole and/or edaravone was, at the time of the
screening visit, started and maintained at a stable regimen for at least 14 days for
riluzole and/or for a full treatment cycle for edaravone;
- Capable of providing informed consent
- Capable and willing to follow trial procedures including visits to the trial clinic
and visit requirements;
- 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
- 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
Exclusion Criteria:
- Presence of tracheostomy or permanent assisted ventilation(PAV)
- Slow Vital Capacity (SVC) less than 55%
- History of known allergy to phenyl butyrate or bile salts
- Abnormal liver function defined as bilirubin levels and/or aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT) > 5 times the upper
limit of the normal (obtained within 12 weeks from first dose)
- Renal insufficiency as defined by eGFR <60 mL/min/1.73m^2 (obtained within 12 weeks
from first dose)
- Pregnant women (confirmed by a pregnancy test within 7 days of first dose) or women
currently breastfeeding
- Current severe biliary disease which may result in the Investigator medical
judgement in biliary obstruction including for example active cholecystitis, primary
biliary cirrhosis, sclerosing cholangitis, gallbladder cancer, gangrene of the
gallbladder, abscess of the gallbladder
- History of Class III/IV heart failure (per New York Heart Association - NYHA)
- Participant under severe salt restriction where the added salt intake due to
treatment would put the participant at risk, in the Investigator clinical judgment
- Presence of unstable psychiatric disease, cognitive impairment, dementia or
substance abuse that would impair ability of the participant to provide informed
consent, according to Investigator judgment
- Clinically significant unstable medical condition (other than ALS) (e.g.,
cardiovascular instability, systemic infection, untreated thyroid dysfunction,
severe laboratory test anomaly or clinically significant electrocardiogram [ECG]
changes) that would pose a risk to the participant if he/she were to participate in
the trial, according to Investigator judgment
- Previous treatment for ALS with cellular therapies or gene therapies
- Currently enrolled in another trial involving use of an investigational therapy
- Previous treatment with PB or taurursodiol within 30 days from Screening
- Implantation of Diaphragm Pacing System (DPS)
- Currently or previously treated within the last 30 days or planned exposure to any
prohibited medications listed in Section 6.8 of the protocol