AMX0035 in Adult Patients With Wolfram Syndrome

Phase 2

Active, not recruiting

• Conditions: Wolfram Syndrome
• Interventions: Drug: AMX0035

• Registration Number: NCT05676034
• Lead Sponsor: Amylyx Pharmaceuticals Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-12-22
• Study First Submitted QC: 2022-12-22
• Study First Posted: 2023-01-09
• Study Start: 2023-03-03
• Primary Completion: 2024-07-23
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-04-02
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AMX0035	AMX0035	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

Primary Outcome Measures

Name	Time	Method
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)	24 weeks	* 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
To assess the safety and tolerability of AMX0035 administered orally for up to 144 weeks in adult participants with Wolfram syndrome	148 weeks	* Incidence and severity of Adverse Events and Serious Adverse Events; * Incidence of abnormalities in clinical laboratory assessments

Secondary Outcome Measures

Name	Time	Method
To evaluate the effect of AMX0035 during a 0-240 minute MMTT	48 weeks	C-peptide AUC response to a 240-minute MMTT at Week 48
To assess the effect of AMX0035 on visual acuity	48 weeks	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
To evaluate the effect of AMX0035 on total daily insulin dose	24 weeks	Change from Baseline of exogenous insulin dose to Week 24
To evaluate the effect of AMX0035 on glucose range	24 weeks	Change from Baseline to Week 24; * Time in good range; * Time below range; * Time above range
To evaluate the effect of AMX0035 on HbA1c levels	24 weeks and 48 weeks	Change from Baseline to Week 24 and Week 48 in HbA1c level

Trial Locations

Locations (1)

Washington University; 🇺🇸 Saint Louis, Missouri, United States