GIVINOSTAT (ITF2357) - A Histone Deacetylase (HDAC) Inhibitor for the treatment of Duchenne

Frequently Asked Questions (FAQs) about this research:


What stage is this research?

  •  A Phase 2 open label clinical trial in boys with Duchenne is ongoing in Italy.  Twenty ambulant boys with Duchenne aged 7 to <11 years at study start and on stable corticosteroid treatment were enrolled and treated for ≥ 36 months with Givinostat. Results after one year of treatment are described below. This clinical trial was conducted to evaluate whether the beneficial histological effects observed with Givinostat in the mdx mouse could be extended to boys with Duchenne.
  • A Phase 3 double blind, placebo controlled trial in ambulant Duchenne boys from 6 years of age is actively recruiting in the USA, Canada and Europe. Trial sites in the USA began opening in June 2017.


Where is this research being done and who is funding this study?

  • Givinostat is being developed by Italfarmaco SpA. The Phase 2 open label study was conducted with the contribution of the European Community through the Endostem project.


What is the goal or purpose of this study?

  • Givinostat is an investigational drug, is a HDAC inhibitor that has the potential to benefit all Duchenne patients regardless of their dystrophin Glossary Link mutation.  
  • HDAC activity is up regulated in dystrophic muscles. This hyperactivity contributes to the impairment of muscle regeneration. HDAC inhibitors stimulate myogenesis in vitro and counter muscle degeneration in mdx mice, promoting the transcription of a number of factors that are key in muscle regeneration such as follistatin. Givinostat has also a potent anti-inflammatory effects.  The combination of Givinostat effects is expected to re-balance the repair process in Duchenne muscle towards an increased muscle regeneration and a reduced fatty infiltration and fibrosis.
  • The main purpose of the upcoming Phase 3 trial is to determine that Givinostat is able to slow the disease progression in Duchenne children. The study will also assess safety and tolerability of the drug. 


What is the current state of this research?

  • Preclinical studies in the mdx mouse model of Duchenne have shown that oral Givinostat dose dependently produced functional and morphological beneficial effects, such as:
    • increased muscle weight,
    • increased cross sectional area of myofibers,
    • decreased inflammatory infiltrate, and fatty replacement,
    • prevention of fibrotic scars,
    • increased membrane stability,
    • increased performance in the treadmill test.
  • Clinical results from a Phase 2 clinical trial in ambulant Duchenne boys aged between 7 and < 11 years old showed that Givinostat significantly counteracted histological disease progression after 12 months of treatment, in particular:
    • It significantly increased muscle fibers size, and it significantly decreased total fibrosis, fatty replacement, necrosis, the mean number of hypercontracted fibers;
    • It significantly increased regenerative fibers with no depletion of the pool of satellite cells.
  • The functional tests showed an overall stability after 12 months of treatment in this population, with small changes in some parameters. Overall the drug was safe and well tolerated. The study is still ongoing, 18 boys have started the fourth year of treatment in July 2015. The results of this phase 2 study, 12 months of treatment were published in Neuromuscular Disorders, in October 2016 (Bettica et al, 26(10):643-649).

What do I have to do if I decide to participate in this study?

  • Participation in this study requires:
    • A brief one page questionnaire that is emailed to you, and returned by email.
    • Blood draw or saliva collected near your home, at UCLA or at your local doctors office.

Where will future trials take place? Will there be study sites in the US?

  • The next clinical trial is a Phase 3 trial in ambulant Duchenne boys and will take place in European and Canadian sites and in about 15 sites in the US. Please check for details regarding the trial sites.


Who would be eligible to participate in a clinical trial?

  • Ambulant Duchenne boys more than 6 years of age. Participants must be on stable corticosteroid for at least 6 months prior to start the treatment and able to perform the 4 stairs climb in not more than 8 seconds. Additional details regarding inclusion and exclusion criteria will be available on (NCT#02851797).


Where can I learn more about Givinostat?

(Updated 9/25/2017)