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

PTC Therapeutics

Status and phase: Withdrawn; Phase 3

Conditions: Duchenne Muscular Dystrophy

Treatments: Drug: Deflazacort

Study type: Interventional

Funder types: Industry

Identifiers

NCT03642145

PTCEMF-GD-003

Details and patient eligibility

About

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.

Sex: Male

Ages: 2 to 4 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Arm A: Deflazacort 0.9 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Deflazacort

Arm B: Deflazacort 0.45 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Deflazacort

Natural History Control Group

No Intervention group

Description:

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.