Treatment of Oculopharyngeal Muscular Dystrophy With Trehalose

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

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.

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).

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.