Wolfram Syndrome
Conditions
Keywords
Wolfram, Wolfram syndrome
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.
Interventions
DRUGAMX0035
AMX0035
Sponsors
Amylyx Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A 144 week open-label treatment period of AMX0035 administered twice daily
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 HbA1c levels | 24 weeks and 48 weeks | Change from Baseline to Week 24 and Week 48 in HbA1c level |
| 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 total daily insulin dose | 24 weeks | Change from Baseline of exogenous insulin dose to Week 24 |
| 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 |
Countries
United States
Outcome results
None listed