A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)

A Multicenter Open-Label Study on the Safety and Efficacy of Deflazacort (Emflaza) in Subjects With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)

This study is designed to evaluate the safety and efficacy of deflazacort in participants with LGMD2I. Most participants enrolled will have a screening visit and 3 additional visits (after 1, 13, and 26 weeks of treatment).

Study Overview

• Status: Terminated
• Conditions: Limb-Girdle Muscular Dystrophy
• Intervention / Treatment: Drug: Deflazacort

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ottawa, Canada, K1Y 4E9
    • Ottawa Hospital
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta
• Denmark
  • Copenhagen, Denmark, 2200
    • Rigshospitalet, University of Copenhagen
• France
  • France, France, 54035
    • CHRU de NANCY Service de Neurologie
  • Marseille, France, 13385
    • University hospital La Timone
• Germany
  • Munich, Germany, 80801
    • Ludwig-Maximilians University Munich, Friedrich-Baur-Institute
• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital
• Russian Federation
  • Moscow, Russian Federation, 125412
    • Pirogov Russian National Research Medical University
  • Saint Petersburg, Russian Federation, 194100
    • Saint-Petersburg State Pediatric Medical University
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Rare Disease Research, LLC
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Hugo W Moser Research Institute at Kennedy Krieger Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Genetic diagnosis of LGMD2I (confirmed mutation in the fukutin-related protein [FKRP] gene).
• Ability to ascend 4 stairs greater than or equal to (≥) 2.5 seconds and be able to complete the ascent and descent both at screening and baseline.
• Ability to understand the nature of the study and the consent form and to comply with study related procedures.
• Must weigh between 35 to 112.5 kilograms (kg).

Exclusion Criteria:

• Received ≥4 weeks of continuous, systemic corticosteroid therapy within 3 months of study screening visit.
• Presence of significant cardiomyopathy as defined by echocardiogram (left ventricular ejection fraction less than (<) 30 percent [%]) at screening.
• Requires fulltime ventilator support.
• History of chronic systemic fungal or viral infections.
• History of recent bacterial infection (including tuberculosis) per discretion of the Investigator.
• Diagnosis of diabetes mellitus (controlled and/or uncontrolled) defined as glycated hemoglobin (HbA1c) ≥6.5% (based on historical or present diagnosis).
• History of immunosuppression or other contraindications to glucocorticosteroid therapy.
• Requires concomitant use or greater than (>) 1 week of drugs or substances that are moderate to strong cytochrome P3A4 (CYP3A4) inhibitors (for example, clarithromycin, fluconazole, diltiazem, verapamil, grapefruit juice) or moderate or strong CYP3A4 inducers (that is, rifampin, efavirenz, carbamazepine, phenytoin) at baseline.
• Participated in an interventional clinical trial within the last 3 months prior the baseline visit.
• Unable or unwilling to comply with the contraceptive requirements of the protocol.
• Female participants who are pregnant and/or breastfeeding.
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, psychiatric, or allergic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deflazacort; Participants will receive deflazacort 0.6 milligrams per kilograms per day (mg/kg/day) orally. The dose could be reduced in case of tolerability issues. Any participant assigned to placebo prior to the Version 4.0 amendment (prior to or after 01 February 2020) will have the option to be consented under Version 4.0 and will be switched to deflazacort for 26 weeks treatment. Any participant assigned to deflazacort prior to the Version 4.0 amendment (prior to 01 February 2020) will have the option to re-consent under Protocol Version 4.0 and continue for an additional 26 weeks treatment. Any participant assigned to deflazacort prior to the Version 4.0 amendment (after 01 February 2020) will have the option to re-consent under Protocol Version 4.0 at their Week 13 Visit and continue treatment until Week 26. Any new participant enrolled until 31 May 2020 will receive deflazacort for 26 weeks.

Drug: Deflazacort; Deflazacort tablet will be administered as per the dose and schedule specified in the arm.; Other Names: Emflaza®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment of Deflazacort		Baseline, Week 26
Change From Baseline in Time to up and go After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in Time to Descend 4 Stairs After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Change From Baseline in Global T2 Relaxation Time of Selected Upper and Lower Limb Muscles After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience.	Baseline up to Week 52
Area Under the Concentration Curve From Time Zero to t (AUC0-t) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Area Under the Concentration Curve From Time Zero to Infinity (AUC0-inf) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Time to Reach Cmax (Tmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Half-Life (t1/2) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Cristobal Passalacqua, MD, PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2019
• Primary Completion (Actual): January 1, 2021
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Deflazacort
• Other Study ID Numbers: PTCEMF-GD-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes