Phase IIIb Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
Research type
Research Study
Full title
A Phase IIIb, Open Label Extension Study Evaluating The Safety And Tolerability of AMX0035 Up To 108 Weeks In Adult Participants with Amyotrophic Lateral Sclerosis (ALS) Previously Enrolled In Study A35-004 (PHOENIX)
IRAS ID
1006648
Contact name
Maria St. Pierre
Contact email
Sponsor organisation
Amylyx Pharmaceuticals Inc.
Eudract number
2022-002348-33
Clinicaltrials.gov Identifier
Research summary
Research Summary
This is an open-label study for participants previously enrolled in Study A35-004 (PHOENIX). All participants will receive open-label treatment with AMX0035 until week 108 or the end of treatment visit. Participants will then be followed up for safety 28 days after the last dose.
A survival follow-up assessment will be completed every 12 weeks following the EOT visit until time of death or EOS.
All participants will be treated with oral (or feeding tube) AMX0035 which comprises of 2 sachets daily (one morning dose and one evening dose) starting on Day 1, for the duration of the study. The study drug is to be mixed with water and taken orally or if applicable, via a feeding tube. If it is noted that twice a day dosing is poorly tolerated, dosing interruptions and reductions may be considered as per protocol
guidance.
The Screening Period is of maximum 6 weeks duration prior to the Baseline Visit (which may be combined with the Week 48 visit of Study A35-004 (PHOENIX).
Overall, the safety and efficacy of edaravone administered by oral and intravenous routes have been demonstrated in many clinical trials in healthy volunteers and ALS patients.
Approximately, 600 patients have been recruited in the main study PHOENIX (21-NREC-CT-022) either randomised to AMX0035 or placebo.
This open-label extension allows previous study participants of the PHOENIX study continued access to AMX0035 for an additional 108 weeks and provides additional evaluation of longitudinal safety and efficacy of treatment with the AMX0035.
The study will also evaluate the effects of the study drug on the participants overall survival, the impact on the participants ALS function and disease progression. Approximately 70 sites in Europe, UK and the US are planned to participate in the
trial.Summary of Results
"We would like to thank everyone who took part in this study. Your involvement made this research possible and has increased understanding about treatment and care of people living with ALS.
Study name: PHOENIX OLE: A Phase IIIb, Open Label Extension Study Evaluating the Safety and Tolerability of AMX0035 for Up to 108 Weeks in Adults With Amyotrophic Lateral Sclerosis (ALS) Who Completed the PHOENIX Study
Study number: A35 011
What was this study about?
PHOENIX OLE was a follow up study for people with ALS who had already finished nearly one year of treatment in the earlier PHOENIX study. The main goal was to see whether AMX0035 continued to be safe when taken for a longer period—up to a little over two years—beyond the earlier study. The study also aimed to understand whether long term treatment with AMX0035 could help people with ALS live longer and delay the need for breathing support from a ventilator.
Unlike the PHOENIX study, there was no placebo group in the PHOENIX OLE study. Everyone knew they were receiving AMX0035.
Why was this research needed?
It is helpful to understand the long-term risks and benefits of a medicine, and open label extension studies like PHOENIX-OLE are a good way to collect this information.
Who sponsored the study?
PHOENIX OLE was sponsored by Amylyx Pharmaceuticals, Inc., a drug development company based in Cambridge, Massachusetts, USA.
Where and when was the study done?
The study took place at 40 centers across Belgium, France, Germany, Ireland, Italy, the Netherlands, Poland, Portugal, Spain, Sweden, and the United Kingdom.
The PHOENIX OLE began in January 2023 and was ended by the sponsor in October 2024.
Who took part?
A total of 353 adults entered the study, and 352 received the study drug.
Participants were adults (age 18 or older) with ALS who had already completed 48 weeks of treatment in the PHOENIX study.
The average age was 59 years, with ages ranging from 21 to 84 years.
About 63% were male and 37% were female. Most were White (78%), with very small numbers from other racial groups (1% or less were Asian, Black or African American, Other, and Unknown); race was not reported for 19% of the participants.
People could not join if they had certain medical conditions, severe salt restrictions, allergies to components of AMX0035, had an implanted diaphragm pacing system (a special device that restores some movement to chest muscle that is important for breathing), or other health issues that the study doctor believed posed risk.
What treatment was studied?
All participants received AMX0035, which is a combination of two drugs—sodium phenylbutyrate (PB) and ursodoxicoltaurine (TURSO). These ingredients are thought to help support the health of cells under stress, which may be relevant in ALS.
What side effects were seen?
Most participants (76%) experienced at least one side effect while taking AMX0035.
About 33% had serious side effects, and 1% (4 people) had a serious side effect that the study doctor believed was related to the drug.
A total of 20% of participants (72 people) died due to side effects; none of these deaths were considered related to AMX0035 by the study doctor.
About 21% of participants stopped taking AMX0035 early because of side effects.
The most common side effects were: Respiratory failure (14%), which is common in people with ALS due to the nature of the disease, and Diarrhea (11%), usually short lasting.
What were the overall results?
While the PHOENIX OLE study was ongoing, results from the earlier PHOENIX study showed that AMX0035 does not provide medical benefit when compared with placebo. Based on those findings, the sponsor, Amylyx Pharmaceuticals, decided to stop the PHOENIX OLE study.
Because the PHOENIX OLE study ended before the participants could complete 108 weeks of treatment with AMX0035, there was not enough information collected to understand whether long term treatment with AMX0035 could help people with ALS live longer and delay the need for breathing support from a ventilator.
No new safety concerns were identified before the study was stopped. The side effects reported were consistent with what is known about ALS and with earlier studies of AMX0035.
Where can I learn more?
More information about this study and similar research may be found on the HRA website, the EU Clinical Trials Register, and ClinicalTrials.gov."REC name
Wales REC 2
REC reference
22/WA/0365
Date of REC Opinion
22 Aug 2023
REC opinion
Further Information Favourable Opinion