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

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ClinicalTrials.gov Identifier: NCT03783923
Recruitment Status : Not yet recruiting
First Posted : December 21, 2018
Last Update Posted : December 21, 2018
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Limb-Girdle Muscular Dystrophy Drug: Deflazacort Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter Randomized Placebo-Controlled Phase III Study on the Safety and Efficacy of Deflazacort (Emflaza®) in Patients With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
Estimated Study Start Date : March 29, 2019
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020


Arm Intervention/treatment
Experimental: Deflazacort
Participants will receive deflazacort 0.6 milligrams per kilograms per day (mg/kg/day) orally for 26 weeks in the double-blind period, and for an additional 26 weeks in the open-label extension period. The initial dose of study drug in double-blind period can be reduced once after Week 13 to the next lower weight-band due to safety or tolerability considerations, regardless of any changes in weight. In the open-label extension period, dose adjustments are permitted at the discretion of the investigator.
Drug: Deflazacort
Deflazacort tablet will be administered as per the dose and schedule specified in the respective arms.
Other Name: Emflaza®

Placebo Comparator: Placebo
Participants will receive placebo matching deflazacort orally for 26 weeks in the double-blind period, and deflazacort 0.6 mg/kg/day for an additional 26 weeks in the open-label extension period. In the open-label extension period, dose adjustments are permitted at the discretion of the investigator.
Drug: Deflazacort
Deflazacort tablet will be administered as per the dose and schedule specified in the respective arms.
Other Name: Emflaza®

Drug: Placebo
Placebo matching deflazacort will be administered as per schedule specified in the respective arm.




Primary Outcome Measures :
  1. Change From Baseline in Time to Climb 4 Stairs at Week 26 [ Time Frame: Baseline, Week 26 ]

Secondary Outcome Measures :
  1. Change From Baseline in Forced Vital Capacity (FVC) at Week 26 [ Time Frame: Baseline, Week 26 ]
  2. Change From Baseline in 2-Minute Walk Test at Week 26 [ Time Frame: Baseline, Week 26 ]
  3. Change From Baseline in Time to up and go at Week 26 [ Time Frame: Baseline, Week 26 ]
  4. Change From Baseline in Time to Descent 4 Stairs at Week 26 [ Time Frame: Baseline, Week 26 ]
  5. Change From Baseline in Time to Run/Walk 10 Meters at Week 26 [ Time Frame: Baseline, Week 26 ]
  6. Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) at Week 26 [ Time Frame: Baseline, Week 26 ]
  7. Change From Baseline in Hand-Held Myometry at Week 26 [ Time Frame: Baseline, Week 26 ]
  8. Number of Participants With Adverse Events [ Time Frame: Baseline to Week 52 ]
  9. Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline to Week 52 ]
  10. Number of Participants With Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline to Week 52 ]
  11. Number of Participants With Ophthalmologic Abnormalities [ Time Frame: Baseline to Week 52 ]
  12. 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 ]
  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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Genetic diagnosis of LGMD2I (confirmed mutation in the fukutin-related protein [FKRP] gene).
  • Ability to ascend 4 stairs greater than (>) 2.5 and less than (<) 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).

Exclusion Criteria:

  • Received greater than or equal to (>=) 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 <30 percent [%]) at screening.
  • Requires fulltime ventilator support.
  • History of chronic systemic fungal or viral infections.
  • History of acute bacterial infection (including tuberculosis).
  • 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 >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 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.

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Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT03783923     History of Changes
Other Study ID Numbers: PTCEMF-GD-004-LGMD
First Posted: December 21, 2018    Key Record Dates
Last Update Posted: December 21, 2018
Last Verified: December 2018

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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

Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophies, Limb-Girdle
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Deflazacort
Anti-Inflammatory Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs