AMX0035 for Wolfram Syndrome

Overseen By Amy Gauger

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Amylyx Pharmaceuticals Inc.

Disqualifiers: Heart failure, Cancer history, Salt restriction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 144 weeks

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have taken any investigational drug or device in the last 30 days, you may not be eligible to participate.

What evidence supports the effectiveness of the drug AMX0035 for treating Wolfram Syndrome?

AMX0035, also known as sodium phenylbutyrate/ursodoxicoltaurine, has shown effectiveness in slowing the progression of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease, in a phase II trial. This suggests potential benefits for other neurodegenerative conditions, although specific data for Wolfram Syndrome is not available. ^{1 2 3 4 5}

How is the drug AMX0035 unique for treating Wolfram Syndrome?

AMX0035 is unique because it combines sodium phenylbutyrate and ursodoxicoltaurine, which may help reduce stress in the endoplasmic reticulum (a part of the cell that helps process proteins), potentially addressing a key issue in Wolfram Syndrome. This approach is different from other treatments like liraglutide, which focuses on improving insulin production and stabilizing neurological symptoms. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is an open label Phase II study to evaluate the safety and efficacy of AMX0035 in adults with Wolfram syndrome.

Research Team

Camille Bedrosian, MD

Principal Investigator

Amylyx Pharmaceuticals

Eligibility Criteria

Adults with Wolfram Syndrome can join this trial. They must be at least 17 years old, have a definitive diagnosis, and need insulin for diabetes caused by the syndrome. Participants should also agree to wear a continuous glucose monitoring (CGM) device throughout the study.

Inclusion Criteria

I have been diagnosed with Wolfram syndrome.

I have diabetes that requires insulin because of Wolfram syndrome.

I am 17 years old or older.

Exclusion Criteria

I haven't taken any experimental drugs or used experimental devices recently.

I have a history of heart failure.

I have conditions affecting bile acid movement due to gut surgery or inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

AMX0035 administered by mouth for 144 weeks: Once daily for first 3 weeks and then twice daily for the remainder of the study if tolerated by participant

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AMX0035

Trial Overview The trial is testing AMX0035's safety and effectiveness in adults with Wolfram Syndrome. It's an open label Phase II study, which means everyone knows they're getting the treatment and there’s no placebo group.

Participant Groups

Group I: AMX0035 Experimental Treatment 1 Intervention

AMX0035 administered by mouth for 144 weeks: Once daily for first 3 weeks and then twice daily for the remainder of the study if tolerated by participant

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+

Findings from Research

The coformulation of sodium phenylbutyrate and ursodoxicoltaurine (ALBRIOZA™) received conditional approval in Canada for treating amyotrophic lateral sclerosis (ALS) based on the results of the phase II CENTAUR trial.

In the CENTAUR trial, sodium phenylbutyrate/ursodoxicoltaurine demonstrated a significant slowing of ALS progression compared to placebo, indicating its potential efficacy in managing this neurodegenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Phenylbutyrate and Ursodoxicoltaurine: First Approval. Heo, YA.[2022]

Relyvrio (sodium phenylbutyrate-taurursodiol) has been approved for treating amyotrophic lateral sclerosis (ALS) based on data from a small phase 2 trial, which showed that it slowed the loss of functioning compared to a placebo.

The drug carries risks for patients sensitive to salt intake and those with disorders related to the pancreas, intestines, or enterohepatic circulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Approved For ALS. Aschenbrenner, DS.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

n of 1 trial for an ornithine transcarbamylase deficiency carrier. [2015]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Sodium Phenylbutyrate and Ursodoxicoltaurine: First Approval. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

New Drug Approved For ALS. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Mild Zellweger syndrome due to functionally confirmed novel PEX1 variants. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Off-Label Liraglutide Use in Children With Wolfram Syndrome Type 1: Extensive Characterization of Four Patients. [2023]

8. Italy pubmed.ncbi.nlm.nih.gov

Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of GLP-1 Agonist Therapy in Autosomal Dominant WFS1-Related Disorder: A Case Report. [2021]

10. Singapore pubmed.ncbi.nlm.nih.gov

Wolfram syndrome: phenotype and novel mutation in two Taiwanese siblings. [2016]