AMX0035 in Adult Patients With Wolfram Syndrome

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

Detailed Description
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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.

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

Conditions
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Wolfram Syndrome

Intervention / Treatment
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* Drug: AMX0035


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A 48 week open-label treatment period of AMX0035 administered twice daily
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMX0035<br>AMX0035 administered by mouth for 48 weeks: Once daily for first 3 weeks and then twice daily for the remainder of the study if tolerated by participant | Drug: AMX0035<br>* AMX0035<br>* Other names: Proprietary formulation of taurursodiol and sodium phenylbutyrate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of AMX0035 during a 0-240 minutes mixed-meal tolerance test (MMTT) | C-peptide AUC response at Week 24 and Week 48 Change from Baseline in C-peptide at Week 24 and Week 48 | 48 weeks | 
| To assess the safety and tolerability of AMX0035in adult participants with Wolfram syndrome | Incidence and severity of Adverse Events and Serious Adverse Events Incidence of abnormalities in clinical laboratory assessments | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect size of AMX0035 on visual acuity | Change from Baseline on best-corrected visual acuity (Logmar) at Week 24 and Week 48 | 48 weeks | 
| To evaluate the effect of AMX0035 on total daily insulin dose | Change from Baseline of exogenous insulin dose to Week 24 and Week 48 | 48 weeks | 
| To evaluate the effect of AMX0035 on glucose range | Change from Baseline to Week 24 and Week 48 Time in good range Time below range Time above range | 48 weeks | 
| To evaluate the effect of AMX0035 on HbA1c levels | Change from Baseline to Week 24 and Week 48 in HbA1c level | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Wolfram, Wolfram syndrome