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

Tracking Information

• First Submitted Date: July 18, 2015
• First Posted Date: August 17, 2015
• Last Update Posted Date: March 12, 2019
• Study Start Date: May 2015
• Actual Primary Completion Date: December 30, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 14, 2015)

• Number of adverse events by severity and relationship [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• Dose reduction or modification due to upper GI or other adverse events [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• Trial discontinuations due to upper GI or other AEs [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• 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
• 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.
• Electrocardiograms [ Time Frame: Every 6 months from enrollment for up to 3 years ]
  Number of subjects with clinically significant changes in QT interval
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 14, 2015)

• Cardiovascular Magnetic Resonance [ Time Frame: Every 6 months from enrollment for up to 3 years ]
  Circumferential strain and myocardial fibrotic areas
• 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.
• Motor function measure (MFM) scale [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• Performance of upper limb (PUL) scale [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• 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.
• Quantitative muscle testing (QMT) scores [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• Timed function tests (TFTs) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• Motor Function Measure (MFM) [ Time Frame: Every 6 months from enrollment for up to 3 years ]
• 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 ]
• 9-hole peg test [ Time Frame: Every 6 months from enrollment for up to 3 years ]
  Assessment of upper limb function and dexterity
• 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.
• Electrical impedance myography (EIM) score [ Time Frame: Every 6 months from enrollment for up to 3 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures (submitted: August 14, 2015): Pharmacokinetics peak plasma concentration (Cmax) [ Time Frame: Pre-dose and 2-4 hour post-dose ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: HT-100 Long-term Study in DMD Patients Who Completed HALO-DMD-02
• Official Title: HT-100 Long-term Safety and Pharmacodynamics in Patients With DMD Who Have Completed Protocols HALO-DMD-01 and HALO-DMD-02
• 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).
• 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
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

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

Study Arms

• Experimental: Cohort 1: HT-100 tablet, Dose 1
  HT-100 multiple dose administration (dose 1).
  Intervention: Drug: HT-100
• Experimental: Cohort 1: HT-100 tablet, Dose 2
  HT-100 multiple dose administration (dose 1).
  Intervention: Drug: HT-100
• Experimental: Cohort 1: HT-100 tablet, Dose 3
  HT-100 multiple dose administration (dose 1).
  Intervention: Drug: HT-100
• Experimental: Cohort 1: HT-100 tablet, Dose 4
  HT-100 multiple dose administration (dose 1).
  Intervention: Drug: HT-100
• Experimental: Cohort 1: HT-100 tablet, Dose 5
  HT-100 multiple dose administration (dose 1).
  Intervention: Drug: HT-100

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 5, 2017): 10
• Original Estimated Enrollment (submitted: August 14, 2015): 30
• Actual Study Completion Date: December 30, 2016
• Actual Primary Completion Date: December 30, 2016 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 6 Years to 20 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02525302
• Other Study ID Numbers: HALO-DMD-03
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Akashi Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Akashi Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Akashi Therapeutics
• Verification Date: March 2019