treatment of oculopharyngeal muscular dystrophy with trehalose

Conditions: Oculopharyngeal Muscular Dystrophy

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.

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).

Eligibility 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. * 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.

Keywords: opmd dmop dysphagia