This study is designed to evaluate the safety and efficacy of deflazacort in participants with LGMD2I. The study will include a 26-week double-blind, randomized, placebo-controlled period followed by a 26-week open-label extension period during which all participants will receive deflazacort.
None
- Change From Baseline in Time to Climb 4 Stairs at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Forced Vital Capacity (FVC) at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in 2-Minute Walk Test at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Time to up and go at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Time to Descent 4 Stairs at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Time to Run/Walk 10 Meters at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) at Week 26 [ Time Frame: Baseline, Week 26 ]
- Change From Baseline in Hand-Held Myometry at Week 26 [ Time Frame: Baseline, Week 26 ]
- Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline to Week 52 ]
- Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline to Week 52 ]
- Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline to Week 52 ]
- Number of Participants With Ophthalmologic Abnormalities [ Time Frame: Baseline 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 ]
- Clearance (CL/F) of 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort [ Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 ]
- Volume of Distribution (Vz/F) of 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort [ Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 ]
- Terminal Elimination Rate Constant (Lambda z [λz]) of 21-desacetyl deflazacort and 6β-hydroxy-21-desacetyl deflazacort [ Time Frame: 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 [ Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 ]
Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
- 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 and less than or equal to (≤) 8 seconds 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 acute bacterial infection (including tuberculosis) per discretion of the Investigator.
- Diagnosis of diabetes mellitus (controlled and/or uncontrolled) defined as glycated hemoglobin (HbA1c) ≥6.5%.
- 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.
United States, Georgia - Rare Disease Research, LLC - Atlanta, Georgia, United States, 30324
United States, Iowa - University of Iowa Hospitals and Clinics - Iowa City, Iowa, United States, 52242
United States, Kansas - The University of Kansas Medical Center - Kansas City, Kansas, United States, 66160
United States, Maryland - Hugo W Moser Research Institute at Kennedy Krieger Institute - Baltimore, Maryland, United States, 21205
United States, Minnesota - University of Minnesota - Minneapolis, Minnesota, United States, 55455
United States, Missouri - Washington University School of Medicine - Saint Louis, Missouri, United States, 63110
United States, Pennsylvania - University of Pennsylvania - Philadelphia, Pennsylvania, United States, 19104
United States, Washington - University of Washington - Seattle, Washington, United States, 98195
Canada, Alberta - University of Alberta - Edmonton, Alberta, Canada, T6G 2G3
Canada - Ottawa Hospital - Ottawa, Canada, K1Y 4E9
Denmark - Rigshospitalet, University of Copenhagen - Copenhagen, Denmark, 2200
France - CHRU de NANCY Service de Neurologie - France, France, 54035
University Hospital La Timone - Marseille, France, 13385
Germany - Ludwig-Maximilians University Munich, Friedrich-Baur-Institute - Munich, Germany, 80801
Norway - Oslo University Hospital - Oslo, Norway, 0424
Russian Federation - Pirogov Russian National Research Medical University - Moscow, Russian Federation, 125412
Saint-Petersburg State Pediatric Medical University - Saint Petersburg, Russian Federation, 194100
Sweden - Sahlgrenska University Hospital - Gothenburg, Sweden, 41345
PTC Therapeutics
Han Phan, Dr
Katherine Mathews
Jeffrey Statland
Kathryn Wagner
Peter Karachunski, Dr.
Conrad Weihl, Dr.
Lauren Elman, Dr.
Seth Perlman, Dr.
Cecile Phan, Dr.
Hanns Lochmuller, Dr.
John Vissing
Maud Michaud, Dr.
Shahram Attarian, Dr.
Maggie Walter, Prof.
Trine Popperud
Dmitry Vlodavets, Dr.
Dmitry Rudenko, Dr.
Christopher Lindberg, Dr.
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