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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 November 2021
• Main ID: NCT03783923
• Date of registration: 19/12/2018
• Prospective Registration: Yes
• Primary sponsor: PTC Therapeutics
• Public title: A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
• Scientific title: A Multicenter Open Label Study on the Safety and Efficacy of Deflazacort (Emflaza®) in Subjects With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
• Date of first enrolment: May 15, 2019
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03783923
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

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

Contacts

• Name: Cristobal Passalacqua, MD
• Affiliation: PTC Therapeutics

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Limb-Girdle Muscular Dystrophy

Intervention(s)

Drug: Deflazacort

Primary Outcome(s)

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

Secondary Outcome(s)

Area Under the Concentration curve From Time Zero to t (AUC0-t) of 21-desacetyl deflazacort and 6ß-hydroxy-21-desacetyl deflazacort [Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13]

Change From Baseline in Time to up and go After 26 Weeks of Treatment [Time Frame: Baseline, Week 26]

Clearance (CL/F) of 21-desacetyl deflazacort and 6ß-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 6ß-hydroxy-21-desacetyl deflazacort [Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13]

Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment [Time Frame: Baseline, Week 26]

Number of Participants With Adverse Events (AEs) [Time Frame: Baseline to Week 52]

Change From Baseline in Hand-Held Myometry 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 Time to Run/Walk 10 Meters After 26 Weeks of Treatment [Time Frame: Baseline, Week 26]

Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl deflazacort and 6ß-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 6ß-hydroxy-21-desacetyl deflazacort [Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13]

Change From Baseline in Time to Descent 4 Stairs After 26 Weeks of Treatment [Time Frame: Baseline, Week 26]

Half-Life (t1/2) of 21-desacetyl deflazacort and 6ß-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 6ß-hydroxy-21-desacetyl deflazacort [Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13]

Number of Participants With Ophthalmologic Abnormalities [Time Frame: Baseline to Week 52]

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 Laboratory Abnormalities [Time Frame: Baseline to Week 52]

Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment [Time Frame: Baseline, Week 26]

Terminal Elimination Rate Constant (Lambda z [?z]) of 21-desacetyl deflazacort and 6ß-hydroxy-21-desacetyl deflazacort [Time Frame: Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13]

Number of Participants With Electrocardiogram (ECG) Abnormalities [Time Frame: Baseline to Week 52]

Secondary ID(s)

PTCEMF-GD-004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors