Treatment of Oculopharyngeal Muscular Dystrophy With Trehalose
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Trehalose Trehalose 9% solution: The dose is 0.75 g/kg administered IV over 60 ± 5 minutes once weekly. |
Drug: Trehalose
90 mg/ml trehalose solution for IV infusion
|
| Placebo Comparator: 0.9% Normal Saline Normal saline: weight-based volume administered IV over 60 ± 5 minutes once weekly. |
Drug: Trehalose
90 mg/ml trehalose solution for IV infusion
|
Outcome Measures
Primary Outcome Measures
- Drinking Test Time [24 weeks]
Change from baseline in timed drinking tests with 80 cc of ice-cold water and nectar.
Secondary Outcome Measures
- Muscle Strength Testing [24 weeks]
Change from baseline in strength tests in selected muscle groups as measured by a handheld dynamometer
- Stair Climb Test [24 weeks]
Change from baseline in functional muscle testing as measured by the Stair Climb test
- Timed Up and Go Test [24 weeks]
Change from baseline in functional muscle testing as measured by the Timed Up and Go (TUG) test
- 30-Second Lift Test [24 weeks]
Change from baseline in functional muscle testing as measured by 30-Second Lift test
- EuroQol-5D-5L [24 weeks]
Change from baseline in health status using the EuroQol-5D-5L Questionnaire
- Swallowing Quality of Life [24 weeks]
Change from baseline in quality of life using modified Swallowing Quality of Life Questionnaire
- Sydney Swallow Questionnaire [24 weeks]
Change from baseline in quality of life using Sydney Swallow Questionnaire
Eligibility Criteria
Criteria
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.
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Treatment with botulinum toxin (any location) within 1 year prior to screening.
-
Diagnosis of any other muscle disorder.
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Prior head and neck surgery or radiation.
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Oropharyngeal injury or oropharyngeal cancer.
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Other esophageal disease that may be the cause of the dysphagia.
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Previously diagnosed with diabetes or a hemoglobin A1c (HgbA1c) result > 6.0% at screening.
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Prior treatment with IV trehalose.
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Known hypersensitivity to trehalose.
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Non-ambulatory (Use of a cane or short leg braces are permitted).
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Prior history of stroke (ischemic or hemorrhagic).
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Pregnancy or breast feeding.
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History of alcohol or drug abuse within the last 5 years.
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Evidence of hepatitis B, hepatitis C, or HIV infection at screening.
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Currently receiving anti-coagulant treatment (e.g., warfarin, enoxaparin) other than anti-platelet treatments, which are not a reason for exclusion.
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Currently participating in another clinical trial or has completed an interventional trial less than 90 days prior to planned first dosing.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ecogene-21 | Chicoutimi | Quebec | Canada | G7H 7K9 |
| 2 | Montreal Neurological Institute and Hospital | Montréal | Quebec | Canada | H3A 2B4 |
| 3 | CHU de Québec-Université Laval- Hôpital Enfant-Jésus | Québec | Quebec | Canada | G1J 1Z4 |
Sponsors and Collaborators
- Bioblast Pharma Ltd.
Investigators
- Principal Investigator: Bernard Brais, MD, McGill University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BB-OPMD-202