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

Overview

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).

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 31, 2021

Interventions

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

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26

Secondary Measures

  • Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Time to up and go After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Time to Descent 4 Stairs After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment
    • Time Frame: Baseline, Week 26
  • Change From Baseline in Global T2 Relaxation Time of Selected Upper and Lower Limb Muscles After 26 Weeks of Treatment
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • PTC Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Cristobal Passalacqua, MD, Study Director, PTC Therapeutics

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