DMD: HT-100 Trial Has Reopened

A trial of an experimental compound to counteract muscle inflammation and scarring in Duchenne MD resumes, after an interruption to complete a dog safety study

Article Highlights:
  • MDA-supported Halo Therapeutics, a subsidiary of DART Therapeutics, has reopened its clinical trial of experimental compound HT-100 in 30 boys and young men with Duchenne muscular dystrophy (DMD).
  • In December 2013, the U.S. Food and Drug Administration had halted the trial after Halo reported preliminary data describing adverse events in dogs being treated with the drug.
  • The five-site, U.S.-based trial will proceed with a conservative approach to dosage increases.
by Margaret Wahl on June 17, 2014 - 12:38pm

Update (July 3, 2014): Akashi says the HT-100 main trial is now closed; the extension study is open to those who have already participated in the main trial.

Update (June 30, 2014): DART Therapeutics and its subsidiary, Halo Therapeutics, have become a single entity, Akashi Therapeutics, located in Cambridge, Mass. The change was announced in a June 24, 2014, press release. The company says the new company name, derived from that of a bridge in Japan, "reflects commitment to bridging the gap between science and medicine to improves the lives of children with Duchenne muscular dystrophy."

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original story:

A trial of an experimental, orally administered compound designed to fight muscle inflammation and scarring and improve muscle regeneration in Duchenne muscular dystrophy (DMD) has resumed, following a temporary hold imposed by the U.S. Food and Drug Administration (FDA) in December 2013.

The drug, HT-100 (delayed-release halofuginone tablet), is being developed by Halo Therapeutics, a Newton, Mass., biotechnology company that has received substantial funding from MDA.

Halo, a subsidiary of DART Therapeutics, a Cambridge, Mass.-based biotechnology firm, received an MDA grant of $500,000 for development of HT-100 in 2013.

‘Conservative approach’ on dose increases

DART and Halo announced the resumption of the phase 1b/2a clinical program of HT-100 in a June 12, 2014, press release.

The U.S. Food and Drug Administration (FDA) had placed the trial on hold late last year after Halo filed a preliminary report of adverse events in a separate study being conducted to test this compound in dogs. There have been no adverse events of concern in the clinical study in boys and young men with DMD.

When asked about whether there will be changes to the clinical trial as a result of the dog study analysis, Halo CEO Marc Blaustein said, “We agreed with the FDA to take a conservative approach to dose escalation [staged increases in dosage level] so that we will have good evidence of safety and tolerability at each dose before escalating to the next higher dose. This was the approach that was designed into the protocol [trial plan] from the start, but we are now evaluating even more data at each of the higher doses before proceeding to the next higher dose. This will slow the rate at which new participants enter the study.”

About the resumed trial

The HT-100 trial is enrolling 30 boys and young men with DMD who are ages 6-20 at five U.S. sites. It will evaluate the safety and tolerability of the drug at a series of increasing dosage levels and will perform biochemical and imaging tests and assess functional abilities. Tests of motor strength and function, as well as pulmonary and cardiac status, will be performed.

All trial participants will receive HT-100, at one of five dosage levels or regimens. There is no placebo group.

After completing the initial, approximately nine-week trial, participants can enter a six-month extension trial.

Trial sites are in Sacramento, Calif.; Baltimore; St. Louis; and Cincinnati and Columbus, Ohio.

New participants in the resumed HT-100 trial must:

  • have a confirmed diagnosis of DMD with minimal to no dystrophin protein being produced;
  • be either ambulatory (able to walk) or non-ambulatory (not able to walk);
  • have been on a stable dose of corticosteroid medication (such as prednisone) prior to study entry or have never been on corticosteroids; and
  • be able to undergo magnetic resonance imaging (MRI).

New participants must not:

  • have had recent, substantial changes in cardiac medications or medications affecting muscle function;
  • have significantly compromised cardiac or respiratory function; or
  • have had prior treatment with any other investigational product in the past six months.

Trial details

As of July 3, the main trial is no longer recruiting new participants. The extension study is accepting patients who have previously participated in the main trial.

For more details about the main study, see Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of HT-100 in Duchenne Muscular Dystrophy; or enter NCT01847573 in the search box at ClinicalTrials.gov.

For details about the extension study, see Open-Label Extension Study of HT-100 in Patients With DMD; or enter NCT01978366 in the search box at ClinicalTrials.gov.

Akashi (new name for Halo as of June 2014) can be contacted at trialinfo@akashirx.com or (617) 431-7250. Email is preferred.

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