Clinical trial NCT05676034: AMX0035 in Adult Patients With Wolfram Syndrome
Official title: A Phase II Study of Safety and Efficacy of AMX0035 in Adult Patients With Wolfram Syndrome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Wolfram Syndrome
Keywords: Wolfram
Wolfram syndrome
Lead sponsor: Amylyx Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-09
Enrollment: 12
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A 144 week open-label treatment period of AMX0035 administered twice daily
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: 24 weeks
measure: To assess the safety and tolerability of AMX0035 administered orally for up to 144 weeks in adult participants with Wolfram syndrome
timeFrame: 148 weeks
Secondary outcomes:
measure: To evaluate the effect of AMX0035 during a 0-240 minute MMTT
timeFrame: 48 weeks
measure: To assess the effect of AMX0035 on visual acuity
timeFrame: 48 weeks
measure: To evaluate the effect of AMX0035 on total daily insulin dose
timeFrame: 24 weeks
measure: To evaluate the effect of AMX0035 on glucose range
timeFrame: 24 weeks
measure: To evaluate the effect of AMX0035 on HbA1c levels
timeFrame: 24 weeks and 48 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Amylyx Pharmaceuticals
name: Camille Bedrosian, MD
role: STUDY_DIRECTOR
References: