Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03783923
Recruitment Status : Completed
First Posted : December 21, 2018
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Tracking Information
First Submitted Date  ICMJE December 19, 2018
First Posted Date  ICMJE December 21, 2018
Last Update Posted Date February 21, 2021
Actual Study Start Date  ICMJE May 15, 2019
Actual Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2020)
Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment [ Time Frame: Baseline, Week 26 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
Change From Baseline in Time to Climb 4 Stairs at Week 26 [ Time Frame: Baseline, Week 26 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2020)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2018)
  • 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 [ 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
Official Title  ICMJE A Multicenter Open Label Study on the Safety and Efficacy of Deflazacort (Emflaza®) in Subjects With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Limb-Girdle Muscular Dystrophy
Intervention  ICMJE Drug: Deflazacort
Deflazacort tablet will be administered as per the dose and schedule specified in the arm.
Other Name: Emflaza®
Study Arms  ICMJE 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.
Intervention: Drug: Deflazacort
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 24, 2020)
30
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2018)
100
Actual Study Completion Date  ICMJE January 31, 2021
Actual Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   France,   Germany,   Norway,   Russian Federation,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03783923
Other Study ID Numbers  ICMJE PTCEMF-GD-004
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PTC Therapeutics
Study Sponsor  ICMJE PTC Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Cristobal Passalacqua, MD PTC Therapeutics
PRS Account PTC Therapeutics
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP