This study has been transitioned to CTIS with ID 2023-508511-23-00 check the CTIS register for the current data. To assess safety and efficacy of AMX0035 for treatment of ALS.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To assess the impact of AMX0035 treatment compared to placebo on disease
progression over 48 weeks based on change form baseline of ALSFRS-R and
survival.
Secondary outcome
1. To assess the impact of AMX0035 compared to placebo on Slow Vital Capacity
(SVC) in adult patients with ALS over 48 weeks; 2. To assess patient quality of
life (QOL; using the 40-item ALS assessment questionnaire [ALSAQ-40]
patient-reported outcome [PRO]) during treatment with AMX0035 compared to
placebo in adult patients with ALS over 48 weeks; 3. To assess AMX0035 compared
to placebo on the time to any decline in King's and MiToS stages as derived
from ALSFRS-R data over 48 weeks; 4. To assess the impact of AMX0035 compared
to placebo on ventilation free survival (defined as death, tracheostomy for
respiratory distress or permanent non-invasive ventilation [>22 hours per day
for 7 consecutive days]) in adult patients with ALS over 48 weeks; 5. To assess
AMX0035 compared to placebo on patient health status (using the EQ-5D
descriptive system and the EQ visual analogue scale [EQ VAS] PRO during
treatment with AMX0035 over 48 weeks. Finally, a secondary objective of the
trial is to assess the long-term overall survival of all-cause mortality beyond
the 48 week Treatment Period of adult patients with ALS treated with AMX0035 or
placebo until time of death or End of Study.
Background summary
ALS is a very serious and fatal condition characterized by progressive
degeneration of the upper and lower motor neurons. There are limited
pharmacological options in the treatment of ALS and they focus on symptom
treatment. The only existing authorized medicine for treating ALS in the
European Union is Riluzole.
In a randomized, Phase II, placebo-controlled trial, AMX0035 administered
orally for 24 weeks as add-on treatment to Investigator selected standard of
care showed statistical significant and clinically meaningful benefit on a
validated functional outcome (ALS Functional Rating Scale-Revised [ALSFRS-R]),
allowing participants to maintain their independence longer. Secondary
endpoints measuring breathing and muscle strength showed effects in the same
direction and with similar magnitude as the primary endpoint although not
statistically significant. AMX0035 did not demonstrate significant safety
concerns and the most notable drug-related adverse events were diarrhea and
nausea.
Study objective
This study has been transitioned to CTIS with ID 2023-508511-23-00 check the CTIS register for the current data.
To assess safety and efficacy of AMX0035 for treatment of ALS.
Study design
This is a Phase III, randomized, double-blind, placebo-controlled trial. Adult
patients with clinically definite or clinically probable ALS according to the
revised El Escorial criteria, meeting all inclusion and exclusion criteria,
will be randomly assigned in a 3:2 ratio to AMX0035 or matching placebo.
Participants will first receive an oral dose of study drug once a day in the
morning (AMX0035 or placebo; one sachet per day) for approximately 14-21 days.
For participants who tolerate the treatment, the dose will then be escalated
(beginning the following day; e.g., Trial Day 15 to 22 or later) to twice a day
oral dosing in the morning and evening (two sachets per day) for the remainder
of a 48-week treatment duration. After the Baseline Visit (Day l), the enrolled
participants will complete an outpatient clinic visit approximately every 12
weeks (+ 2 weeks) at Week 12, Week 24, Week 36, and Week 48/End of Trial.
Because it is anticipated that the ongoing Coronavirus disease (COVID-19)
pandemic will continue to affect many sites, alternatively the actual site
visits may be conducted using telemedicine or as a home visit by a site nurse
or staff per local practice and allowances. Other trial assessments will be
performed at 4-week and 12-week intervals.
Intervention
Participants will be randomly assigned in a3:2 ratio to oral (or feeding tube)
AMX0035 treatment (a fixed-dose combination of sodium phenylbutyrate [PB] and
taurursodiol) or matching placebo. For the first 14 to 21 days of dosing,
participants will take I sachet daily and if tolerated will increase to
2 sachets daily.
AMX0035 or matching placebo will be supplied by Amylyx to the site pharmacy as
a carton box containing single use sachets. Each AMX0035 sachet contains active
ingredients in a powder formulation with 3 g PB and 1 g taurursodiol. Study
drug powder is mixed with water and taken orally
(or via feeding tube).
Study burden and risks
The study drug may have side effects. It cannot be excluded that side effects
can be serious, long lasting or may never go away. All efforts will be used to
reduce any discomfort from participation in this study. The following side
effects have been found in patients with ALS during previous studies using
AMX0035 (occurs in 1 out of 10 people, or more):
- Diarrhea
- Constipation
- Nausea
- Weakness of the muscles
- Fall
- Headache
- Dizziness
- Viral infections of the upper respiratory tract
The most common side effects of AMX0035 found in patients with ALS during
previous studies are diarrhea and nausea (approximately 1 out of 5 people). The
study drug may also cause side effects that are unknown.
Other disadvantages can be possible adverse effects/discomforts of the tests
and procedures applied in the study. In addition, the patient and caregiver
have to invest time in participation in the study. The patient has to attend
clinic visits for the required study visits, undergo testing procedures, and be
available for phone or video calls.
Advantages: The patients current condition of ALS will be assessed carefully.
The study drug may slow down ALS disease progression, but this is not certain.
It may be that participation in this study does not provide any benefit for the
patient's health. However, the patient will contribute to increase the
knowledge about the treatment of ALS.
Thorndike St. 43
Cambridge MA 02141
US
Thorndike St. 43
Cambridge MA 02141
US
Listed location countries
Age
Inclusion criteria
1. Male or female, at least 18 years of age; 2. Diagnosis of ALS (clinically
definite or clinically probable), made by a physician who is experienced with
management of ALS, as defined by the World Federation of Neurology revised El
Escorial criteria; 3. Time since onset of first symptom of ALS should be <24
months prior to randomization; Date of ALS symptom onset is defined as the
onset of weakness (in the limbs, bulbar region, or trunk). Weakness in the
bulbar region includes dysarthria and dysphagia; 4. 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 Baseline
Visit, previously started and maintained at a stable regimen for at least 14
days for riluzole and/or for a full treatment cycle for edaravone; 5. Capable
of providing informed consen[ 6. Capable and willing to follow trial procedures
including visits to the trial clinic remote visits, and survival status
reporting requirements; 7. Women of childbearing potential (WOCBP; 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 trial and 3 months after the
last dose of study drug; 8. Women must not be pregnant or planning to become
pregnant for the duration of the trial and 3 months after last dose of study
drug; 9. Men must agree to practice contraception for the duration of the trial
and for at least 3 months after last dose of study drug; 10. Men must not plan
to father a child or to provide sperm for donation for the duration of the
trial and 3 months after the last dose of study drug;
Exclusion criteria
1. Presence of tracheostomy or PAV; defined as >22 hours daily of mechanical
ventilation for more than 1 week (7 days); 2. Slow Vital Capacity (SVC) less
than 55%; 3. History of known allergy to phenylbutyrate or bile salts; 4.
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); 5.5.
Renal insufficiency as defined by estimated glomerular filtration rate (eGFR)
<60 mL/min/1.73m2 (from a local laboratory within 12 weeks or central
laboratory within 6 weeks from first dose at the Baseline Visit); 6. Pregnant
women (confirmed by a pregnancy test within 7 days prior to first dose) or
women currently breastfeeding; 7. 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 ofthe gallbladder, abscess ofthe
gallbladder; 8. History of Class III/IV heart failure (per New York Heart
Association - NYHA); 9. Participant under severe salt restriction where the
added salt intake due to treatment would put the participant at risk, in the
Investigator clinical judgment; 10. 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; 11. Clinically significant unstable medical condition (other than
ALS) (e.g., cardiovascular instability, systemic infection, untreated thyroid
dysfunction, clinically significant laboratoy test or ECG abnormality) that
would pose a risk to the participant if he/she were to participate in the
trial, according to Investigator judgment; 12. Previous treatment for ALS with
cellular therapies or gene therapies; 13. Currently enrolled on another trial
involving use of an investigational therapy; (or within 5.5 plasma half-lives)
prior to first dose at Baseline Visit; 14. 14. Previous treatment with sodium
phenylbutyrate (PB) or taurursodiol within 30 days from first dose at Baseline
Visit; 15. Implantation of Diaphragm Pacing System (DPS); 16. Currently or
previously treated within the last 30 days (or 5 half-lives, whichever is
longer) from first dose at the Baseline Visit or planned exposure during the
treatment period to any prohibited medications listed in Section 6.7 of the
protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-508511-23-00 |
| EudraCT | EUCTR2021-000250-26-NL |
| ClinicalTrials.gov | NCT05021536 |
| CCMO | NL78255.100.21 |