AMX0035 in Adult Patients With Wolfram Syndrome

A Phase II Study of Safety and Efficacy of AMX0035 in Adult Patients With Wolfram Syndrome

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

Study Overview

• Status: Active, not recruiting
• Conditions: Wolfram Syndrome
• Intervention / Treatment: Drug: AMX0035

Detailed Description

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 to evaluate the effect of AMX0035 on residual beta cell functions by monitoring c-peptide levels during a 0-240 minute mixed-meal tolerance test. The trial will also assess the effects of AMX0035 on changes to diabetic measurements including daily insulin dose, time in good glucose range, and HbA1c levels. Effect on best-corrected visual acuity in both eyes will also be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Definitive diagnosis of Wolfram syndrome
• Insulin dependent diabetes mellitus due to Wolfram syndrome
• At least 17 years of age
• Participant must be willing to wear a CGM device for the duration of the study

Key Exclusion Criteria:

• Presence of pathologies that can alter the enterohepatic circulation of bile acids (e.g., ileal resection and stoma, regional ileitis)
• Any history of heart failure per New York Heart Association (NYHA)
• History of or family history of breast and/or ovarian cancer
• Participant under severe salt restriction where the added salt intake due to treatment would put the patient at risk, in the Investigator's judgment
• Received treatment with any investigational drug or device within the 30 days (or 5 half-lives, whichever is longer) prior to first dose at Day 1
• Previous treatment with gene or cellular therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMX0035; AMX0035 administered by mouth for 208 weeks: Once daily for first 3 weeks and then twice daily for the remainder of the study if tolerated by participant	Drug: AMX0035; AMX0035; Other Names: Proprietary formulation of taurursodiol and sodium phenylbutyrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of AMX0035 on residual beta-cell function by monitoring C-peptide levels during a 0-240 minutes mixed-meal tolerance test (MMTT)	C-peptide area under the curve (AUC) response at Week 24 using a 0-240 minute MMTT; Change from Baseline in area under the curve (AUC) in delta C-peptide at Week 24 using a 0-240 minute MMTT	24 weeks
To assess the safety and tolerability of AMX0035 administered orally for up to 208 weeks in adult participants with Wolfram syndrome	Incidence and severity of Adverse Events and Serious Adverse Events; Incidence of abnormalities in clinical laboratory assessments	208 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of AMX0035 on total daily insulin dose	Change from Baseline of exogenous insulin dose to Week 24	24 weeks
To evaluate the effect of AMX0035 on glucose range	Change from Baseline to Week 24; Time in good range; Time below range; Time above range	24 weeks
To evaluate the effect of AMX0035 during a 0-240 minute MMTT	C-peptide AUC response to a 240-minute MMTT at Week 48	48 weeks
To assess the effect of AMX0035 on visual acuity	Change from Baseline on best-corrected visual acuity for both eyes measured on the LogMAR scale by sight tests using Snellen chart at Week 48	48 weeks
To evaluate the effect of AMX0035 on HbA1c levels	Change from Baseline to Week 24 and Week 48 in HbA1c level	24 weeks and 48 weeks

Collaborators and Investigators

• Sponsor: Amylyx Pharmaceuticals Inc.
• Investigators: Study Director: Camille Bedrosian, MD, Amylyx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Actual): July 23, 2024
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: December 22, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Wolfram syndrome; Wolfram
• Additional Relevant MeSH Terms: Urogenital Diseases; Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Eye Diseases; Neurodegenerative Diseases; Eye Diseases, Hereditary; Congenital Abnormalities; Otorhinolaryngologic Diseases; Vision Disorders; Sensation Disorders; Abnormalities, Multiple; Heredodegenerative Disorders, Nervous System; Ear Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Pituitary Diseases; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Blindness; Optic Atrophies, Hereditary; Optic Atrophy; Diabetes Insipidus; Diabetes Mellitus, Type 1; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Wolfram Syndrome; Antineoplastic Agents; 4-phenylbutyric acid; sodium phenylbutyrate and taurursodiol
• Other Study ID Numbers: A35-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No