Treatment of Oculopharyngeal Muscular Dystrophy With Trehalose

Study Overview
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Brief Summary
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BB-OPMD-202 is a randomized, double-blind, placebo-controlled study of IV trehalose for treatment of OPMD. The study includes a 4-week screening period, a 24-week blinded treatment period during which patients will receive weekly infusions of trehalose or placebo, followed by a 24-week open-label extension period during which all patients will receive weekly infusions of trehalose. Patients will undergo a safety follow-up assessment 4 weeks after their last treatment.

Detailed Description
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After signing informed consent, patients will undergo two rounds of ice-cold water and nectar drinking tests at least 1 week apart to confirm oropharyngeal dysfunction. Patients who have confirmed oropharyngeal dysfunction, i.e., an ice-cold water drinking test time of 8 seconds or greater at both rounds, in addition to an SSQ score of >235, will be enrolled. Baseline values for all safety and efficacy parameters will be established during the screening period. Patients will be randomized in a 1:1 ratio, to trehalose or placebo, at the time of enrollment. Randomization will be stratified according to the patient's score on the SSQ at screening (≤ 799 or ≥ 800). Patients randomized to trehalose will receive a 1-hour IV infusion of trehalose at a dose of 0.75 g/kg weekly for 24 weeks. Patients randomized to placebo (normal saline) will receive a weight-based equal volume of placebo weekly for 24 weeks. After Week 24, patients may transition to an open-label extension of the study (extension period). During the extension period, patients will be treated with weekly infusion of trehalose at a dose of 0.75 g/kg for 24 weeks, followed by a 4-week safety follow-up (total duration of study = 56 weeks).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Trial of Trehalose for the Treatment of

Conditions
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Oculopharyngeal Muscular Dystrophy

Intervention / Treatment
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* Drug: Trehalose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetically confirmed OPMD with a (GCN)13 size PABPN1 mutation A score greater than 235 on the Sydney Swallow Questionnaire at screening Confirmation of oropharyngeal dysfunction by abnormal ice-cold water drinking test result, defined as drinking 80 cc of ice-cold water in ≥ 8 seconds at both drinking tests (at least 1 week apart) during the screening period Exclusion Criteria: History of pharyngeal myotomy. Esophageal dilatation within the last 12 months. Treatment with botulinum toxin (any location) within 1 year prior to screening. Diagnosis of any other muscle disorder. Prior head and neck surgery or radiation. Oropharyngeal injury or oropharyngeal cancer. Other esophageal disease that may be the cause of the dysphagia. Previously diagnosed with diabetes or a hemoglobin A1c (HgbA1c) result > 6.0% at screening. Prior treatment with IV trehalose. Known hypersensitivity to trehalose. Non-ambulatory (Use of a cane or short leg braces are permitted). Prior history of stroke (ischemic or hemorrhagic). Pregnancy or breast feeding. History of alcohol or drug abuse within the last 5 years. Evidence of hepatitis B, hepatitis C, or HIV infection at screening. Currently receiving anti-coagulant treatment (e.g., warfarin, enoxaparin) other than anti-platelet treatments, which are not a reason for exclusion. Currently participating in another clinical trial or has completed an interventional trial less than 90 days prior to planned first dosing.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study includes a 24-week blinded treatment period during which patients will receive weekly infusions of trehalose or placebo, followed by a 24-week open-label extension period during which all patients will receive weekly infusions of trehalose.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trehalose<br>Trehalose 9% solution: The dose is 0.75 g/kg administered IV over 60 ± 5 minutes once weekly. | Drug: Trehalose<br>* 90 mg/ml trehalose solution for IV infusion<br>|
| Placebo Comparator: 0.9% Normal Saline<br>Normal saline: weight-based volume administered IV over 60 ± 5 minutes once weekly. | Drug: Trehalose<br>* 90 mg/ml trehalose solution for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinking Test Time | Change from baseline in timed drinking tests with 80 cc of ice-cold water and nectar. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Strength Testing | Change from baseline in strength tests in selected muscle groups as measured by a handheld dynamometer | 24 weeks | 
| Stair Climb Test | Change from baseline in functional muscle testing as measured by the Stair Climb test | 24 weeks | 
| Timed Up and Go Test | Change from baseline in functional muscle testing as measured by the Timed Up and Go (TUG) test | 24 weeks | 
| 30-Second Lift Test | Change from baseline in functional muscle testing as measured by 30-Second Lift test | 24 weeks | 
| EuroQol-5D-5L | Change from baseline in health status using the EuroQol-5D-5L Questionnaire | 24 weeks | 
| Swallowing Quality of Life | Change from baseline in quality of life using modified Swallowing Quality of Life Questionnaire | 24 weeks | 
| Sydney Swallow Questionnaire | Change from baseline in quality of life using Sydney Swallow Questionnaire | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OPMD, DMOP, Dysphagia