Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of HT-100 in Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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The main purpose of this study is to test the safety and tolerability of different, increasing doses of an experimental medication called HT-100 in boys and young men with Duchenne muscular dystrophy (DMD). The study medication, HT-100, is a medicine that may help promote healthy muscle regeneration, diminish inflammation and the resulting damage to muscle, and decrease the scar tissue that forms in the muscles of children with DMD. In this study, pharmacokinetic sampling, or measurements of the amount of HT-100 in the bloodstream will also be taken.

Official Title
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A Phase 1b Open Label, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-100 in Patients With Duchenne Muscular Dystrophy

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: HT-100


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Ambulatory or non-ambulatory Diagnosis of DMD with confirmation of minimal to no dystrophin Corticosteroid naive or on therapy for at least 12 months (stable dose and regimen) Main Exclusion Criteria: Recent, substantial change in use of cardiac medications or medications affecting muscle function Inability to undergo magnetic resonance imaging (MRI) Significantly compromised cardio-respiratory function Prior treatment with another investigational product in past 6 months

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 20 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: HT-100 tablet, Dose 1<br>Single dose administration: Dose 1 Multiple dose administration: Dose 1 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|
| Experimental: Cohort 2: HT-100 tablet, Dose 2<br>Single dose administration: Dose 2 Multiple dose administration: Dose 2 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|
| Experimental: Cohort 3: HT-100 tablet, Dose 3<br>Single dose administration: Dose 3 Multiple dose administration: Dose 3 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|
| Experimental: Cohort 4a: HT-100 tablet, Dose 4<br>Single dose administration: Dose 4 Multiple dose administration: Dose 4 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|
| Experimental: Cohort 4b: HT-100 tablet, Dose 5<br>* Multiple dose administration: Dose 5 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|
| Experimental: Cohort 5: HT-100 tablet, Dose 6<br>* Multiple dose administration: Dose 5 | Drug: HT-100<br>* May be administered in either fed or fasted state<br>* Other names: halofuginone hydrobromide delayed-release tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of administering single and multiple ascending doses of HT-100 in DMD boys | Safety profile by review of adverse events (AEs), physical examination findings, clinical laboratory test results, and other diagnostic testing | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic plasma profile of halofuginone after single and multiple dose administration of HT-100 in DMD boys | Halofuginone plasma concentrations | 1 week | 
| Safety and tolerability of administering multiple ascending doses of HT-100 in DMD boys over 4 weeks | Safety profile by review of AEs, physical examination findings, clinical laboratory test results, and other diagnostic testing | 4 weeks | 
| Early pharmacodynamic signals of HT-100 after 4 weeks of continuous dosing in DMD boys | Pharmacodynamic measures relevant to DMD pathology: Pulmonary function Motor function Muscle composition Biochemical and imaging markers | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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halofuginone hydrobromide, anti-fibrotic, anti-inflammatory, muscle regeneration, protein synthesis inhibitor