AMX0035 for ALS

(Phoenix Trial)

Not currently recruiting at 80 trial locations

Overseen By Amylyx Trial Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amylyx Pharmaceuticals Inc.

Must be taking: Riluzole, Edaravone

Must not be taking: PB, Taurursodiol

Disqualifiers: Tracheostomy, Renal insufficiency, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMX0035 for people with ALS, a disease that affects nerve cells in the brain and spinal cord, causing muscle weakness. Researchers aim to determine if AMX0035 is safe and effective for treating ALS symptoms. Participants will receive either AMX0035 or a placebo (a substance with no active treatment) to compare effects. Those diagnosed with ALS within the last 24 months and able to follow trial procedures might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to help potentially bring a new treatment to market.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but if you are on riluzole or edaravone, you must have been on a stable dose for at least 14 days or a full treatment cycle, respectively. Check with the trial team for any specific medications that might be prohibited.

Is there any evidence suggesting that AMX0035 is likely to be safe for humans?

Research has shown that AMX0035 has undergone safety testing in people with ALS (Amyotrophic Lateral Sclerosis). Previous studies found that AMX0035, a combination of phenylbutyrate and ursodoxicoltaurine, was generally well-tolerated. The primary goal was to confirm its safety for long-term use. Most participants managed the treatment without serious issues, and while some experienced side effects, these were mostly mild. If someone cannot tolerate the treatment, adjustments such as changing the dosage can be made. Overall, the safety data so far suggests AMX0035 could be a safe option for people with ALS. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Researchers are excited about AMX0035 for ALS because it combines two compounds, sodium phenylbutyrate and taurursodiol, which may protect nerve cells from damage. Unlike standard ALS treatments like riluzole or edaravone, which mainly aim to slow disease progression, AMX0035 targets both neuronal inflammation and cell death pathways, potentially offering a more comprehensive approach. This dual-action mechanism could mean more effective management of ALS symptoms and improved quality of life for patients.

What evidence suggests that AMX0035 might be an effective treatment for ALS?

Research has shown that AMX0035, one of the treatments studied in this trial, may help treat ALS, a progressive nerve disease. In earlier studies, participants taking AMX0035 experienced a slower decline in physical abilities compared to those taking a placebo, which contains no active medicine. The CENTAUR study found that AMX0035 was safe and helped slow the disease's progression. AMX0035 consists of two ingredients, sodium phenylbutyrate and taurursodiol, which work together to protect nerve cells from damage. These findings suggest that AMX0035 could be a beneficial option for managing ALS symptoms. ^{1 3 4 6 7}

Who Is on the Research Team?

Amylyx Study Director

Principal Investigator

Amylyx Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with ALS within the last 2 years who can consent and follow study procedures. They must use birth control during the study and not plan to conceive. Excluded are pregnant or breastfeeding women, those with severe medical conditions, on salt restriction, enrolled in other trials, using prohibited meds, or have specific health issues like low lung capacity or poor kidney function.

Inclusion Criteria

I can and will follow all trial procedures and visit requirements.

My first ALS symptoms appeared less than 2 years ago.

I have been diagnosed with ALS.

Exclusion Criteria

I haven't taken PB or taurursodiol in the last 30 days.

Currently enrolled in another trial involving use of an investigational therapy

My kidney function is low, with an eGFR under 60.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMX0035 or placebo for 48 weeks to evaluate safety and efficacy in ALS treatment

48 weeks

Once daily for first 3 weeks, then twice daily

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Long-term survival will be monitored by assessing all-cause mortality

3 years from LPI

What Are the Treatments Tested in This Trial?

Interventions

• AMX0035
• Placebo

Trial Overview The Phoenix Trial is testing AMX0035 against a placebo to see if it's safe and effective for treating ALS. This Phase III trial randomly assigns participants to either receive AMX0035 or a placebo without them knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: AMX0035 Experimental Treatment 1 Intervention

Placebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

Group II: Placebo Placebo Group 1 Intervention

Placebo administered by mouth or via feeding tube for 48 weeks: once daily for first 3 weeks and then twice daily for remainder of study if participant tolerating

AMX0035 is already approved in United States, Canada for the following indications:

Approved in United States as Relyvrio for:

• Amyotrophic Lateral Sclerosis

Approved in Canada as Albrioza for:

• Amyotrophic Lateral Sclerosis

Who Is Running the Clinical Trial?

Amylyx Pharmaceuticals Inc.

Lead Sponsor

Trials

12

Recruited

1,600+

Citations

1. amylyx.com amylyx.com/news/amylyx-pharmaceuticals-announces-topline-results-from-global-phase-3-phoenix-trial-of-amx0035-in-als

Amylyx Pharmaceuticals Announces Topline Results From ... The Phase 3 PHOENIX study enrolled 664 adults living with ALS. Participants were randomized three-to-two to receive either AMX0035 or placebo.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602655/

Clinical Review - Sodium phenylbutyrate-ursodoxicoltaurine ... The primary safety outcome of the CENTAUR study was to confirm the safety and tolerability of PB-TURSO while the primary efficacy outcome was the rate of change ...

3. amylyx.com amylyx.com/document/encals-preclinical-data-poster-final.pdf

Efficacy of Sodium Phenylbutyrate and Ursodoxicoltaurine ... Variants in the actin polymerization protein profilin 1 (PFN1) have been implicated as a genetic cause of amyotrophic lateral sclerosis ...

4. icer.org icer.org/wp-content/uploads/2022/02/ICER-ALS-Final-Report-09152022.pdf

AMX0035 and Oral Edaravone for Amyotrophic Lateral ... Model results therefore represent average findings across patients and should not be presumed to represent the clinical or cost outcomes for any.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/216660Orig1s000Med_StatR.pdf

216660Orig1s000 CLINICAL AND STATISTICAL REVIEW(S) The proposed indication for AMX0035 is for the treatment of amyotrophic lateral sclerosis (ALS). ... effectiveness of sodium phenylbutyrate/taurursodiol (AMX0035) ...

6. ec.europa.eu ec.europa.eu/health/documents/community-register/2024/20240105160995/anx_160995_en.pdf

Albrioza, INN-Sodium phenylbutyrate/Ursodoxicoltaurine AMX0035 is a fixed-dose combination consisting of phenylbutyrate (PB) and ursodoxioltaurine (TURSO). It is hypothesized to reduce neuronal cell death and ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603373/

Sodium Phenylbutyrate and Ursodoxicoltaurine (Albrioza) CADTH recommends that Albrioza be reimbursed by public drug plans for the treatment of patients with amyotrophic lateral sclerosis (ALS) if certain conditions