Halofuginone HT-100

A randomised, double-blind, placebo-controlled, multiple-dose, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of HT-100 in patients with Duchenne muscular dystrophy.

Marc B Blaustein MPP
Halo Therapeutics LLC, USA

Saturday 15th October 2011

Halofuginone (HT-100) has been shown in experimental animals to possess antifibrotic, anti-inflammatory and muscle regenerative effects. Early clinical studies with topical administration show evidence of an antifibrotic effect in humans, and human studies with oral administration also show evidence of expected biological activity. Investigations in adult healthy volunteers and cancer patients showed frequent nausea and vomiting occurring at high doses, but with no serious toxicity. Clinical studies show that the nausea and vomiting can be managed by dividing daily doses into smaller individual doses. Halo proposes a Phase II, randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study in Duchenne boys. The primary objective is to investigate safety and tolerability. Secondary objectives are the pharmacokinetic profile and several clinical and biological measures of efficacy, including muscle biopsies.

TACT considered the proposal to be ready for the clinic and extraordinarily well prepared, and is enthusiastic about the potential of the compound based on the proposed mechanism. Given the limited amount of long-term tolerability data, TACT advised to start the trial with a dose-escalating tolerability and pharmacokinetics phase, followed by a longer second phase addressing efficacy on a biological and clinical level. While all patients are planned to be on standard treatment with corticosteroids, interaction with other drugs frequently applied in Duchenne MD also have to be considered. TACT agreed with the Sponsor that nausea and vomiting make repeated small daily dosages and/or appropriate drug formulation necessary for avoiding untoward gastro-intestinal interactions. Repeated biopsies seem to be inevitable to quantify fibrosis at the present stage of drug development; however additional less invasive outcome measures, such as standardised MRI, are also recommended. FDA should be approached as soon as possible with the aim to discuss acceptable clinical outcome measures.

12 Apr 2017