A Study of Deflazacort (Emflaza®) in Participants With Duchenne Muscular Dystrophy (DMD) (PTCEMF)

A 52-Week Phase 3B Randomized Open-Label Study Evaluating the Safety and Pharmacokinetics of Emflaza® (Deflazacort) Compared to a Comparable Natural History Control Group in Males Aged ≥2 to <5 Years With Duchenne Muscular Dystrophy (DMD) Followed by a 52-Week Extension Period

The primary objective of this study is to evaluate the safety of a 0.9 milligrams per kilogram (mg/kg) and 0.45 mg/kg daily dose of deflazacort with a comparable natural history control group after 52 weeks of treatment in males with DMD aged greater than or equal to (>=) 2 to lesser than (<) 5 years.

The study will comprise of 2 periods (Period 1: 52-week safety and pharmacokinetics [PK], and Period 2: 52-week extension). Participants will be randomized in a 1:1 ratio to one of 2 treatment arms: 0.9 mg/kg deflazacort, and 0.45 mg/kg of deflazacort. A historic control group (which should match the study population as closely as possible) will be used as a comparator to characterize the safety and tolerability of deflazacort.

Study Overview

• Status: Withdrawn
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Deflazacort

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• In the opinion of the Investigator, the participant and parent(s)/caregiver are capable of complying with protocol requirements.
• The participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• The participant must have a diagnosis of DMD defined by genetic or biopsy confirmation of DMD or have documented, increased serum creatine kinase more than 40 times the upper limit of normal (ULN) and shown phenotypic signs of DMD.
• The participant weighs between 11 kilograms (kg) and 50 kg at screening visit.
• Ability to comply with scheduled visits, oral drug administration, and study procedures.
• The participant is current on childhood vaccinations according to the Center for Disease Control (CDC) recommended immunizations for children from birth through 6 years old. Note: The investigator should discuss timing of receipt of the varicella vaccine with the caregiver prior to initiation of chronic steroid treatment. Administration of live or live attenuated vaccines is not recommended in participants receiving immunosuppressive doses of corticosteroids. Participants whose caregivers decline vaccinations as a matter of personal belief may be included.
• Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, and vital signs at screening, as deemed by the Investigator.
• The participant is able to ingest the oral tablets either whole or crushed.

Exclusion Criteria:

• The participant has received 4 weeks or more of continuous corticosteroid therapy within 3 months of study screening visit.
• The participant has, in the judgment of the Investigator, clinically significant abnormal clinical laboratory parameters at screening or baseline that may affect safety.

• The participant has, in the judgment of the Investigator, a history or current medical condition that could affect safety including, but not limited to:

  1. Major renal or hepatic impairment
  2. Immunosuppression or other contraindications for corticosteroid treatment
  3. History of chronic systemic fungal or viral infections
  4. Diabetes mellitus or significant glucose intolerance
  5. Idiopathic hypercalciuria
  6. Symptomatic cardiomyopathy Note: Elective surgeries can be discussed with medical monitor.
• The participant has a history of hypersensitivity or allergic reaction to steroids or their formulations including, but not limited to lactose, sucrose, etc.
• The participant has received any drug, including prescription and non-prescription medications, and herbal remedies known to be significant inhibitors and/or inducers of cytochrome P3A4 (CYP3A4) enzymes and/or P glycoprotein (P-gp) 14 days prior to the first dose of study drug.
• The participant has an indication that requires long-term use of strong CYP3A4 inhibitors and/or inducers that would interfere with the pharmacokinetics of deflazacort.
• The participant has received any investigational compound and/or has participated in another clinical study within 30 days prior to study treatment with the exception of observational cohort studies or non-interventional studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Deflazacort 0.9 mg/kg; Participants will receive approximately 0.9 mg/kg deflazacort once daily orally for 52 weeks in Period 1 and for 52 weeks in Period 2. The target dose could be varied +/- 20 percent (%) depending upon the available tablet strengths and change in participant's weight.	Drug: Deflazacort; Deflazacort tablets will be administered as per schedule and dose specified in respective arms.; Other Names: Emflaza®
Experimental: Arm B: Deflazacort 0.45 mg/kg; Participants will receive approximately 0.45 mg/kg deflazacort once daily orally for 52 weeks in Period 1. Participants will either continue to receive 0.45 mg/kg deflazacort or escalated dose of deflazacort (0.9 mg/kg) once daily orally in Period 2 at the investigator's discretion and in consultation with the caregiver. The target dose could be varied +/- 20% depending upon the available tablet strengths and change in participant's weight.	Drug: Deflazacort; Deflazacort tablets will be administered as per schedule and dose specified in respective arms.; Other Names: Emflaza®
No Intervention: Natural History Control Group; Control participants matching to the study population as closely as possible, will be used as a comparator to characterize the safety and tolerability of deflazacort.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Period 1 and 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	52 weeks
Period 1 and 2: Change From Baseline in Vital Signs and Electrocardiogram (ECG) at Week 52	Baseline, Week 52
Period 1 and 2: Change From Baseline in the Child Behavior Checklist Score at Week 52	Baseline, Week 52
Period 1 and 2: Change From Baseline in the Normalized Measure of Bone Density Change (Z-score) for the Dual Energy X-ray Absorptiometry (DEXA) at Week 52	Baseline, Week 52
Period 1 and 2: Mean Change From Baseline in Height at Week 52	Baseline, Week 52
Period 1 and 2: Mean Change From Baseline in Body Weight at Week 52	Baseline, Week 52
Period 1 and 2: Mean Change From Baseline in Height Percentile for Age at Week 52	Baseline, Week 52
Period 1 and 2: Number of Participants With Clinically Significant Laboratory Tests	52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Period 1: Peak Plasma Concentration (Cmax) of Deflazacort	Pre-dose, 0.25, 2, 4, and 6 hours post-dose at Baseline (Week 1) and Week 13
Period 1: Area Under the Curve (AUC) of Deflazacort	Pre-dose, 0.25, 2, 4, and 6 hours post-dose at Baseline (Week 1) and Week 13
Period 1: Volume of Distribution (Vd) of Deflazacort	Pre-dose, 0.25, 2, 4, and 6 hours post-dose at Baseline (Week 1) and Week 13
Period 1: Clearance (CL) of Deflazacort	Pre-dose, 0.25, 2, 4, and 6 hours post-dose at Baseline (Week 1) and Week 13

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Francesco Bibbiani, MD, PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2018
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: July 10, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 22, 2018

Study Record Updates

• Last Update Posted (Actual): June 21, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Deflazacort
• Other Study ID Numbers: PTCEMF-GD-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No