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

Limb-Girdle Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03783923
• Other study ID #: PTCEMF-GD-004
• Status: Terminated
• Phase: Phase 3
• Start date: October 31, 2019
• Est. completion date: January 1, 2021

Study information

• Verified date: May 2022
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: January 1, 2021
• Est. primary completion date: January 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Limb-Girdle Muscular Dystrophy
• Muscular Dystrophies

Intervention

Drug:
• Deflazacort
Deflazacort tablet will be administered as per the dose and schedule specified in the arm.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
Canada	Ottawa Hospital	Ottawa
Denmark	Rigshospitalet, University of Copenhagen	Copenhagen
France	CHRU de NANCY Service de Neurologie	France
France	University Hospital La Timone	Marseille
Germany	Ludwig-Maximilians University Munich, Friedrich-Baur-Institute	Munich
Norway	Oslo University Hospital	Oslo
Russian Federation	Pirogov Russian National Research Medical University	Moscow
Russian Federation	Saint-Petersburg State Pediatric Medical University	Saint Petersburg
Sweden	Sahlgrenska University Hospital	Gothenburg
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Hugo W Moser Research Institute at Kennedy Krieger Institute	Baltimore	Maryland
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	University of Minnesota	Minneapolis	Minnesota
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Norway,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment of Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Time to up and go After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Time to Descend 4 Stairs After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment With Deflazacort		Baseline, Week 26
Secondary	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
Secondary	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
Secondary	Area Under the Concentration Curve From Time Zero to t (AUC0-t) of 21-desacetyl Deflazacort and 6ß-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Secondary	Area Under the Concentration Curve From Time Zero to Infinity (AUC0-inf) of 21-desacetyl Deflazacort and 6ß-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Secondary	Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl Deflazacort and 6ß-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Secondary	Time to Reach Cmax (Tmax) of 21-desacetyl Deflazacort and 6ß-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13
Secondary	Half-Life (t1/2) of 21-desacetyl Deflazacort and 6ß-hydroxy-21-desacetyl Deflazacort		Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13