Clinical trial NCT03783923: A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
Official title: A Multicenter Open-Label Study on the Safety and Efficacy of Deflazacort (Emflaza) in Subjects With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Limb-Girdle Muscular Dystrophy
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-12-21
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment of Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Time to up and go After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Time to Descend 4 Stairs After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Change From Baseline in Global T2 Relaxation Time of Selected Upper and Lower Limb Muscles After 26 Weeks of Treatment With Deflazacort
timeFrame: Baseline, Week 26
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 52
measure: Area Under the Concentration Curve From Time Zero to t (AUC0-t) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
measure: Area Under the Concentration Curve From Time Zero to Infinity (AUC0-inf) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
measure: Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
measure: Time to Reach Cmax (Tmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
measure: Half-Life (t1/2) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort
timeFrame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Hugo W Moser Research Institute at Kennedy Krieger Institute
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Ottawa
country: Canada
facility: Ottawa Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet, University of Copenhagen
city: France
country: France
facility: CHRU de NANCY Service de Neurologie
city: Marseille
country: France
facility: University Hospital La Timone
city: Munich
country: Germany
facility: Ludwig-Maximilians University Munich, Friedrich-Baur-Institute
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Pediatric Medical University
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: PTC Therapeutics
name: Cristobal Passalacqua, MD
role: STUDY_DIRECTOR
References: