A Natural History Study In Chinese Male Patients With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a multicenter, prospective, single cohort study designed to describe the natural history of DMD in Chinese male patients. A total of approximately 330 subjects will be enrolled with the target number of subjects in each group as below: Group 1, Ambulatory subjects aged <6 years, approximately 100 subjects; Group 2, Ambulatory subjects aged >=6 years, approximately 180 subjects; Group 3, Non-ambulatory subjects, approximately 50 subjects. Subjects will visit sites every 6 months. Each subject will be observed for at least 24 months. All subjects will remain enrolled until the study completion date, such that some will have data collected after Month 24. Subjects, who complete Visit 5/Month 24 at least 6 months prior to study completion, will be asked to complete an additional visit at Month 30.

Official Title
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A NATURAL HISTORY STUDY IN CHINESE MALE PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Other: Visit frequency


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese male patients with any age, diagnosed with DMD. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor). Subjects who are >=4 years old must be receiving glucocorticosteroids for a minimum of 6 months prior to signing informed consent. There should be no significant change (<0.2 mg/kg) in dosage or dose regimen (not related to body weight change) for at least 3 months immediately prior to signing the informed consent. Subjects who are aged >4 years will be exempt from this requirement; those not taking GC will be eligible if the initiation of GC treatment in these subjects is considered inappropriate in the opinion of Investigators. Exclusion Criteria: Any injury which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months from injury date. Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary, cardiac, and cognitive diseases. Subjects >=4 years old who have not completed the varicella vaccination. Participation in other studies involving investigational drug(s) for a minimum of 90 days prior to signing the informed consent and/or during study participation.

Ages Eligible for Study
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Minimum Age: 0 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Study arm<br>All subjects in this study will be observed for 24-30 months. | Other: Visit frequency<br>* All subjects need to visit sites more frequently than in routine clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to life altering clinical milestones due to DMD disease progression - failure to walk |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Time to life altering clinical milestones due to DMD disease progression - failure to stand |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Time to life altering clinical milestones due to DMD disease progression - failure to self feed |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in timed motor functions for ambulatory subjects - rise from floor (supine to stand) |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in timed motor functions for ambulatory subjects - 10 meter walk/run |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in clinical evaluator determined scales - Northstar Ambulatory Assessment | The Northstar Ambulatory Assessment will be performed in ambulatory children >=3 years old | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in clinical evaluator determined scales - Performance of Upper Limb 2.0 | The Performance of Upper Limb 2.0 will be administered in subjects >=10 years old. | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in strength of muscle groups - knee extension |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in strength of muscle groups - elbow flexion |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in strength of muscle groups - elbow extension |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in strength of muscle groups - shoulder abduction. |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in pulmonary function tests - Percent predicted Forced Vital Capacity (%pFVC) |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in pulmonary function tests - Forced Expiratory Volume in one Second |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in pulmonary function tests - Maximum Inspiratory Pressure |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in pulmonary function tests - Maximum Expiratory Pressure |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in pulmonary function tests - Peak cough flow |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in range of motion (ROM) at bilateral ankles and elbows |  | Change from baseline, 6, 12, 18, 24, 30 Months | 
| Change from Baseline in left ventricular ejection fraction (LVEF) |  | Change from baseline, 12, 24, 30 Months | 
| Change from Baseline in Wechsler Intelligence Scale for Children (WISC) score in ambulatory subjects aged >=6 years to <=16 years | The WISC is individually administered intelligence test for children between ages of 6 and 16. It generates a Full Scale Intelligence Quotient. | Chang from baseline, 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with mutation of large deletion |  | Baseline | 
| Proportion of subjects with mutation of large duplication |  | Baseline | 
| Proportion of subjects with mutation of small insertion |  | Baseline | 
| Proportion of subjects with mutation of small deletion |  | Baseline | 
| Proportion of subjects with mutation of point mutation |  | Baseline | 
| Proportion of subjects with mutations involving key high frequency mutation sites |  | Baseline | 
| Change from Baseline in Pediatric Outcomes Data Collection Instrument (PODCI) score | The Pediatric Outcomes Data Collection Instrument is a patient-reported assessment of musculoskeletal health intended for use in children and adolescents. | Baseline, 12, 24, 30 Months | 
| Change from Baseline in EuroQoL 5 Dimension 3 Level (EQ-5D-3L) | The EQ-5D-3L is instrument measuring health-related quality of life for patients >=16 years old. | Baseline, 12, 24, 30 Months | 
| Change from Baseline in EuroQoL 5 Dimension Youth (EQ-5D-Y) | EQ-5D-Y is a generic instrument measuring health-related quality of life in children and adolescents younger than 16 years old and able to read and complete the questionnaire. | Baseline, 12, 24, 30 Months | 
| Change from Baseline in Healthcare Resource Utilization (HRU) score | The result collection is based on the HRU questionnaire. | Baseline, 12, 24, 30 Months | 
| Change from Baseline in Work Productivity and Activity Impairment Questionnaire adapted for Caregiving (WPAI:CG) impairment scores | WPAI:CG will measure the impact of a subject with DMD on a caregiver's work productivity and regular activities. It will be administered as questionnaire. | Baseline, 12, 24, 30 Months |