Oculopharyngeal Muscular Dystrophy
Conditions
Keywords
OPMD, DMOP, Dysphagia
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.
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).
Interventions
DRUGTrehalose
90 mg/ml trehalose solution for IV infusion
Sponsors
Bioblast Pharma Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Treatment Period of the study is double-blind. The Extension Period is open label.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
50 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinking Test Time | 24 weeks | Change from baseline in timed drinking tests with 80 cc of ice-cold water and nectar. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Sydney Swallow Questionnaire | 24 weeks | Change from baseline in quality of life using Sydney Swallow Questionnaire |
| 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 |
| 30-Second Lift Test | 24 weeks | Change from baseline in functional muscle testing as measured by 30-Second Lift test |
Countries
Canada
Outcome results
None listed