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.

Study Overview

• Status: Withdrawn
• Conditions: Oculopharyngeal Muscular Dystrophy
• Intervention / Treatment: Drug: Trehalose

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Montréal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Quebec-Universite Laval- Hopital Enfant-Jesus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bioblast Pharma Ltd.
• Investigators: Principal Investigator: Bernard Brais, MD, McGill University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Anticipated): February 15, 2018
• Study Completion (Anticipated): August 15, 2018

Study Registration Dates

• First Submitted: July 15, 2019
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Dysphagia; OPMD; DMOP
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Oculopharyngeal
• Other Study ID Numbers: BB-OPMD-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No