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

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

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).

Study Overview

• Status: Terminated
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: HT-100

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute, Johns Hopkins School of Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Completed both previous studies HALO-DMD-01 and HALO-DMD-02
2. Ability to provide written informed consent
3. 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.

1. 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
2. History of severe allergic or anaphylactic reactions
3. Recent report of drug/alcohol abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: HT-100 tablet, Dose 1; HT-100 multiple dose administration (dose 1).	Drug: HT-100; 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.; Other Names: halofuginone hydrobromide
Experimental: Cohort 1: HT-100 tablet, Dose 2; HT-100 multiple dose administration (dose 1).	Drug: HT-100; 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.; Other Names: halofuginone hydrobromide
Experimental: Cohort 1: HT-100 tablet, Dose 3; HT-100 multiple dose administration (dose 1).	Drug: HT-100; 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.; Other Names: halofuginone hydrobromide
Experimental: Cohort 1: HT-100 tablet, Dose 4; HT-100 multiple dose administration (dose 1).	Drug: HT-100; 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.; Other Names: halofuginone hydrobromide
Experimental: Cohort 1: HT-100 tablet, Dose 5; HT-100 multiple dose administration (dose 1).	Drug: HT-100; 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.; Other Names: halofuginone hydrobromide

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics peak plasma concentration (Cmax)	Pre-dose and 2-4 hour post-dose

Collaborators and Investigators

• Sponsor: Akashi Therapeutics
• Investigators: Study Director: Diana M Escolar, MD, Askashi Therapeutics

Publications and helpful links

Helpful Links

• Sponsor company website

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 30, 2016
• Study Completion (Actual): December 30, 2016

Study Registration Dates

• First Submitted: July 18, 2015
• First Submitted That Met QC Criteria: August 14, 2015
• First Posted (Estimate): August 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 12, 2019
• Last Update Submitted That Met QC Criteria: March 8, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: neuromuscular; DMD; Duchenne
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Coccidiostats; Halofuginone
• Other Study ID Numbers: HALO-DMD-03