HT-100 Long-term Study in DMD Patients Who Completed HALO-DMD-02

Study Overview
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Brief Summary
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This study, HALO-DMD-03, is a follow-on study to HALO-DMD-01 and HALO-DMD-02, and allows continued open-label access to HT-100 for subjects who have completed these studies. HALO-DMD-03 will provide safety and strength and function data on continuous long-term dosing. Data from this study will be used to inform the safety, tolerability, and dose selection for a future trial of HT-100 in boys with Duchenne Muscular Dystrophy (DMD).

Detailed Description
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As a follow-on study to the initial clinical studies of HT-100 in DMD (Protocols HALO-DMD-01 and HALO-DMD-02), this open-label study is designed to provide data on continuous long-term dosing. Subjects will be entered into the study without cessation of dosing, in a staggered fashion, into the same cohort assignment they had in the predecessor studies. Up to 30 subjects who have completed dosing in HALO-DMD-02 will be offered the opportunity to continue on the same dose regimen until market approval of HT-100 or termination of the study by the Sponsor. Reasons for termination could include, among others, safety concerns or lack of efficacy, based on analysis of combined data from all HT-100 studies. Safety data from subjects approaching the end the HALO-DMD-02 participation will be individually reviewed by the Medical Monitor and the subject's physician (Principal Investigator [PI]). If the Medical Monitor and the PI agree there are no clinically significant safety signals (absence of clinically significant laboratory or clinical abnormalities to date), the subject will be considered eligible and offered continuation of dosing. To avoid an interruption in dosing, subjects will immediately be screened for participation and enrolled upon completing the predecessor trial, HALO-DMD-02. Participation is in this study HALO-DMD-03 is optional. Safety and pharmacodynamics (PD) monitoring will continue throughout the subject's study participation. Dose reduction/modification might occur or individual subjects' participation in the trial may be discontinued if any Adverse Events (AEs) suggest that HT-100 is not sufficiently well tolerated.

Official Title
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HT-100 Long-term Safety and Pharmacodynamics in Patients With DMD Who Have Completed Protocols HALO-DMD-01 and HALO-DMD-02

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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Inclusion Criteria: Completed both previous studies HALO-DMD-01 and HALO-DMD-02 Ability to provide written informed consent Ability to understand and follow site and protocol instruction for the entire duration of the study Exclusion Criteria: Answering yes to any of the following make the subject NOT eligible to participate in the study. Clinically significant major disease not related to DMD that would make it not safe to be in the study or affect ability to follow the protocol History of severe allergic or anaphylactic reactions Recent report of drug/alcohol abuse

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>HT-100 multiple dose administration (dose 1). | Drug: HT-100<br>* HT-100 is Akashi Therapeutics' proprietary delayed-release formulation of halofuginone hydrobromide, a small molecule therapeutic with anti-fibrotic properties. May be administered in either fed or fasted state. Not mutation specific.<br>* Other names: halofuginone hydrobromide;|
| Experimental: Cohort 1: HT-100 tablet, Dose 2<br>HT-100 multiple dose administration (dose 1). | Drug: HT-100<br>* HT-100 is Akashi Therapeutics' proprietary delayed-release formulation of halofuginone hydrobromide, a small molecule therapeutic with anti-fibrotic properties. May be administered in either fed or fasted state. Not mutation specific.<br>* Other names: halofuginone hydrobromide;|
| Experimental: Cohort 1: HT-100 tablet, Dose 3<br>HT-100 multiple dose administration (dose 1). | Drug: HT-100<br>* HT-100 is Akashi Therapeutics' proprietary delayed-release formulation of halofuginone hydrobromide, a small molecule therapeutic with anti-fibrotic properties. May be administered in either fed or fasted state. Not mutation specific.<br>* Other names: halofuginone hydrobromide;|
| Experimental: Cohort 1: HT-100 tablet, Dose 4<br>HT-100 multiple dose administration (dose 1). | Drug: HT-100<br>* HT-100 is Akashi Therapeutics' proprietary delayed-release formulation of halofuginone hydrobromide, a small molecule therapeutic with anti-fibrotic properties. May be administered in either fed or fasted state. Not mutation specific.<br>* Other names: halofuginone hydrobromide;|
| Experimental: Cohort 1: HT-100 tablet, Dose 5<br>HT-100 multiple dose administration (dose 1). | Drug: HT-100<br>* HT-100 is Akashi Therapeutics' proprietary delayed-release formulation of halofuginone hydrobromide, a small molecule therapeutic with anti-fibrotic properties. May be administered in either fed or fasted state. Not mutation specific.<br>* Other names: halofuginone hydrobromide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events by severity and relationship |  | Every 6 months from enrollment for up to 3 years | 
| Dose reduction or modification due to upper GI or other adverse events |  | Every 6 months from enrollment for up to 3 years | 
| Trial discontinuations due to upper GI or other AEs |  | Every 6 months from enrollment for up to 3 years | 
| Vital signs (Number of subjects with clinically significant changes) | Number of subjects with clinically significant changes | Every 6 months from enrollment for up to 3 years | 
| Laboratory values (Number of subjects with clinically significant changes) | Number of subjects with clinically significant changes. | Every 6 months from enrollment for up to 3 years | 
| Electrocardiograms | Number of subjects with clinically significant changes in QT interval | Every 6 months from enrollment for up to 3 years | 
| Echocardiograms | Number of subjects with clinically significant changes in left ventricular ejection fraction, end systolic and diastolic interventricular septal thickness, left ventricular posterior wall thickness | Every 6 months from enrollment for up to 3 years | 
| Cardiovascular Magnetic Resonance | Number of subjects with clinically significant change in diagnostic interpretation | Every 6 months from enrollment for up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Magnetic Resonance | Circumferential strain and myocardial fibrotic areas | Every 6 months from enrollment for up to 3 years | 
| Pulmonary function testing (Number of subjects with clinically significant changes) | Number of subjects with clinically significant changes. | Every 6 months from enrollment for up to 3 years | 
| Motor function measure (MFM) scale |  | Every 6 months from enrollment for up to 3 years | 
| Performance of upper limb (PUL) scale |  | Every 6 months from enrollment for up to 3 years | 
| Biomarkers of extracellular matrix turnover (Number of subjects with clinically significant changes) | Number of subjects with clinically significant changes. | Every 6 months from enrollment for up to 3 years | 
| Quantitative muscle testing (QMT) scores |  | Every 6 months from enrollment for up to 3 years | 
| Timed function tests (TFTs) |  | Every 6 months from enrollment for up to 3 years | 
| Motor Function Measure (MFM) |  | Every 6 months from enrollment for up to 3 years | 
| Upper extremity function (proximal, mid-range, and distal) by Performance of Upper Limb (PUL) |  | Every 6 months from enrollment for up to 3 years | 
| 9-hole peg test | Assessment of upper limb function and dexterity | Every 6 months from enrollment for up to 3 years | 
| Tip pinch and key pinch tests (Number of subjects with clinically significant changes) | Number of subjects with clinically significant changes. | Every 6 months from enrollment for up to 3 years | 
| Electrical impedance myography (EIM) score |  | Every 6 months from enrollment for up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMD, neuromuscular, Duchenne