A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
- Registration Number
- NCT03783923
- Lead Sponsor
- PTC Therapeutics
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Deflazacort 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort Baseline, Week 26
- Secondary Outcome Measures
Name Time Method 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) Baseline up to Week 52 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.
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
Trial Locations
- Locations (18)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Rigshospitalet, University of Copenhagen
🇩🇰Copenhagen, Denmark
Hugo W Moser Research Institute at Kennedy Krieger Institute
🇺🇸Baltimore, Maryland, United States
Rare Disease Research, LLC
🇺🇸Atlanta, Georgia, United States
Pirogov Russian National Research Medical University
🇷🇺Moscow, Russian Federation
Oslo University Hospital
🇳🇴Oslo, Norway
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
CHRU de NANCY Service de Neurologie
🇫🇷France, France
Ottawa Hospital
🇨🇦Ottawa, Canada
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University Hospital La Timone
🇫🇷Marseille, France
Saint-Petersburg State Pediatric Medical University
🇷🇺Saint Petersburg, Russian Federation
Ludwig-Maximilians University Munich, Friedrich-Baur-Institute
🇩🇪Munich, Germany
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden