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

• ClinicalTrials.gov Identifier: NCT02525302
• Recruitment Status: Terminated
• First Posted: August 17, 2015
• Last Update Posted: March 12, 2019
• Sponsor: Akashi Therapeutics
• Information provided by (Responsible Party): Akashi Therapeutics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: HT-100	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HT-100 Long-term Safety and Pharmacodynamics in Patients With DMD Who Have Completed Protocols HALO-DMD-01 and HALO-DMD-02
• Study Start Date: May 2015
• Actual Primary Completion Date: December 30, 2016
• Actual Study Completion Date: December 30, 2016

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: halofuginone hydrobromide

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Cardiovascular Magnetic Resonance [ Time Frame: Every 6 months from enrollment for up to 3 years ]
   Circumferential strain and myocardial fibrotic areas
2. Pulmonary function testing (Number of subjects with clinically significant changes) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
   Number of subjects with clinically significant changes.
3. Motor function measure (MFM) scale [ Time Frame: Every 6 months from enrollment for up to 3 years ]
4. Performance of upper limb (PUL) scale [ Time Frame: Every 6 months from enrollment for up to 3 years ]
5. Biomarkers of extracellular matrix turnover (Number of subjects with clinically significant changes) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
   Number of subjects with clinically significant changes.
6. Quantitative muscle testing (QMT) scores [ Time Frame: Every 6 months from enrollment for up to 3 years ]
7. Timed function tests (TFTs) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
8. Motor Function Measure (MFM) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
9. Upper extremity function (proximal, mid-range, and distal) by Performance of Upper Limb (PUL) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
10. 9-hole peg test [ Time Frame: Every 6 months from enrollment for up to 3 years ]
    Assessment of upper limb function and dexterity
11. Tip pinch and key pinch tests (Number of subjects with clinically significant changes) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
    Number of subjects with clinically significant changes.
12. Electrical impedance myography (EIM) score [ Time Frame: Every 6 months from enrollment for up to 3 years ]

Other Outcome Measures:

1. Pharmacokinetics peak plasma concentration (Cmax) [ Time Frame: Pre-dose and 2-4 hour post-dose ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

University of California, Davis Medical Center

Sacramento, California, United States, 95817

United States, Maryland

Kennedy Krieger Institute, Johns Hopkins School of Medicine

Baltimore, Maryland, United States, 21205

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Sponsors and Collaborators

Akashi Therapeutics

Investigators

• Study Director: Diana M Escolar, MD; Askashi Therapeutics

More Information

Additional Information:

Sponsor company website 

• Responsible Party: Akashi Therapeutics
• ClinicalTrials.gov Identifier: NCT02525302
• Other Study ID Numbers: HALO-DMD-03
• First Posted: August 17, 2015
• Last Update Posted: March 12, 2019
• Last Verified: March 2019

Keywords provided by Akashi Therapeutics:

DMD; neuromuscular; Duchenne

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Halofuginone; Antineoplastic Agents; Coccidiostats; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors