Givinostat for Duchenne Muscular Dystrophy

Not currently recruiting at 45 trial locations

Age: Any Age

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Italfarmaco

Must be taking: Givinostat

Must not be taking: Growth hormone

Disqualifiers: Heart failure, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety and effectiveness of Givinostat, a medication for Duchenne Muscular Dystrophy (DMD), a condition that causes muscle weakness and loss. Participants will take Givinostat orally twice daily to evaluate its efficacy and safety over time. Individuals who participated in previous Givinostat studies for DMD and met specific study requirements may qualify to join. As a Phase 2, Phase 3 trial, this study is crucial for assessing the treatment's effectiveness in a larger group and serves as a key step before potential FDA approval, offering participants an opportunity to advance DMD treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using any medications other than corticosteroids that might affect muscle strength or function within 3 months before joining the study. Vitamin D, calcium, and other supplements are allowed.

Is there any evidence suggesting that Givinostat is likely to be safe for humans?

Research shows that Givinostat has been tested in patients with Duchenne muscular dystrophy (DMD) who can walk. In one study with 179 patients, Givinostat was generally well-tolerated, though some patients experienced side effects. Common issues included upset stomach and headache, usually mild.

Givinostat has been approved by the FDA for treating DMD in patients aged 6 and older. This approval indicates the treatment is considered safe enough for use, although it does carry some risks. Reports of serious side effects exist, but these are less common.

For those considering joining a trial, these findings suggest that while there are some risks, Givinostat has been thoroughly studied and is deemed safe enough for treating DMD. Always discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Duchenne muscular dystrophy?

Givinostat is unique because it offers a new approach to treating Duchenne Muscular Dystrophy by targeting the inflammatory process involved in muscle degeneration. Unlike standard treatments like corticosteroids, which primarily aim to slow disease progression and manage symptoms, Givinostat works by inhibiting histone deacetylase (HDAC), potentially reducing muscle inflammation and fibrosis. Researchers are excited about Givinostat because it promises not only to slow muscle damage but also to improve muscle strength and function, which could significantly enhance the quality of life for patients.

What evidence suggests that Givinostat might be an effective treatment for Duchenne Muscular Dystrophy?

Research has shown that Givinostat, which participants in this trial will receive, can help slow down Duchenne Muscular Dystrophy (DMD). Studies have found that patients taking Givinostat reached major disease milestones later than those not on the treatment. In one study, Givinostat proved more effective than a placebo in improving movement abilities, such as walking for six minutes and getting up from the floor. Long-term data suggest that Givinostat can significantly delay the disease's progression, offering hope for those with DMD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for boys aged ≥6 with Duchenne Muscular Dystrophy who've been in a previous Givinostat study. They must have specific muscle fat levels, be able to consent, and use contraception if needed. Excluded are those with hypersensitivity to the drug's components, certain intolerances or diseases, heart failure, liver issues, psychiatric conditions affecting compliance, recent non-steroid muscle treatments, other neurological disorders or abnormal blood tests.

Inclusion Criteria

Must have participated in one of the previous studies with GIVINOSTAT in DMD and have attended the End of Study Visit or must have been screened in study DSC/14/2357/48 and met all the inclusion criteria and none of the exclusion criteria

Never been randomized because the enrollment in the off-target group was completed

I am 6 years old or older.

Exclusion Criteria

I am not using any experimental drugs except Givinostat.

I do not have any other serious illnesses that could interfere with the study.

Baseline QTcF >450 msec or history of additional risk factors for torsades de pointes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GIVINOSTAT oral suspension (10 mg/mL) twice daily in a fed state. Dosage adjustments based on weight and platelet count monitoring.

1 year

Weekly visits for the first month, bi-weekly for the second month, then as needed

Follow-up

Participants are monitored for safety and effectiveness after treatment, with specific attention to adverse events and stabilization of any treatment-related issues.

4 weeks

Open-label extension

Long-term continuation of GIVINOSTAT treatment for safety, tolerability, and efficacy assessment in DMD patients.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Givinostat

Trial Overview The trial is testing the long-term safety and effectiveness of Givinostat in patients with Duchenne Muscular Dystrophy. It's an open-label study meaning everyone knows they're getting Givinostat and it focuses on those who've previously taken part in related studies.

How Is the Trial Designed?

Group I: givinostat Experimental Treatment 1 Intervention

Givinostat oral suspension (10 mg/mL) twice daily in a fed state

Givinostat is already approved in United States for the following indications:

Approved in United States as Duvyzat for:

• Duchenne muscular dystrophy (DMD) in patients 6 years of age and older

Who Is Running the Clinical Trial?

Italfarmaco

Lead Sponsor

Trials

36

Recruited

4,500+

Cromsource

Industry Sponsor

Trials

18

Recruited

3,200+

Published Research Related to This Trial

Givinostat, a histone deacetylase inhibitor, showed significant improvements in muscle biopsy parameters in boys with Duchenne muscular dystrophy (DMD) during a Phase II study, indicating its potential efficacy in treating this condition.

The pharmacokinetic model developed from seven clinical studies suggests that dosing of givinostat should be adjusted based on body weight, and monitoring platelet counts is essential, as about 14-15% of patients experienced a significant decrease in platelet count after 6 months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic-pharmacodynamic analysis of givinostat. Fiorentini, F., Germani, M., Del Bene, F., et al.[2023]

Long-term treatment with the HDAC inhibitor givinostat in mdx mice, a model for Duchenne muscular dystrophy, showed effective recovery of muscle function and structure at doses between 5 and 10 mg/kg/day, while lower doses (1 mg/kg/day) were less effective.

Givinostat treatment led to increased muscle cross-sectional area, reduced fibrosis and fatty infiltration, improved endurance in treadmill tests, and decreased inflammation in the muscles, supporting its potential as a therapeutic option for muscular dystrophies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical studies in the mdx mouse model of duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat. Consalvi, S., Mozzetta, C., Bettica, P., et al.[2021]

Givinostat has been shown to promote mitochondrial biogenesis in dystrophic muscle by modifying the epigenetic profile of the PGC-1α promoter, which is crucial for energy production in cells.

The study identifies two phases of mitochondrial damage in Duchenne Muscular Dystrophy, highlighting the importance of targeting both early mitochondrial mass depletion and later accumulation of dysfunctional mitochondria to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Givinostat as metabolic enhancer reverting mitochondrial biogenesis deficit in Duchenne Muscular Dystrophy. Giovarelli, M., Zecchini, S., Catarinella, G., et al.[2022]

Givinostat-treated muscle progenitor cells (Givi-MPC) derived from human induced pluripotent stem cells (hiPSCs) showed enhanced proliferation and migration abilities compared to control cells, indicating their potential for effective muscle repair in Duchenne muscular dystrophy (DMD).

Transplantation of Givi-MPC into injured muscle in mice resulted in significant restoration of dystrophin, reduced inflammation, and less muscle damage, demonstrating their therapeutic efficacy in repairing muscle tissue affected by DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pluripotent stem cell-induced skeletal muscle progenitor cells with givinostat promote myoangiogenesis and restore dystrophin in injured Duchenne dystrophic muscle. Xuan, W., Khan, M., Ashraf, M.[2023]

In a study using mdx mice, low doses of prodrugs combining arginine and butyrate significantly improved muscle function, with force and fatigue resistance increasing by approximately 60% and 3.5-fold, respectively, while also reducing heart muscle necrosis by about 90%.

The treatment also enhanced muscle membrane integrity and increased levels of utrophin and other important proteins in both mice and human myotubes, demonstrating that these low-dose prodrugs effectively target the nitric oxide pathway and inhibit histone deacetylases, offering a promising approach for treating Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low doses of arginine butyrate derivatives improve dystrophic phenotype and restore membrane integrity in DMD models. Vianello, S., Consolaro, F., Bich, C., et al.[2014]

In a study involving 20 ambulant boys with Duchenne Muscular Dystrophy (DMD), treatment with Givinostat for over 12 months significantly increased muscle tissue and reduced fibrotic tissue, indicating a positive histological effect.

The treatment was found to be safe and well-tolerated, although no improvements in functional tests were observed, suggesting that while Givinostat may help with muscle structure, further research is needed to assess its impact on muscle function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histological effects of givinostat in boys with Duchenne muscular dystrophy. Bettica, P., Petrini, S., D'Oria, V., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40830818/

Long-Term Evaluation of Givinostat in Duchenne Muscular ... Comparisons with natural history data suggest that givinostat delays the occurrence of major disease progression milestones. Trial registration: ...

2. prnewswire.com prnewswire.com/news-releases/new-data-presented-on-givinostat-for-treatment-of-duchenne-muscular-dystrophy-at-2025-neuromuscular-study-group-annual-scientific-meeting-302567931.html

New Data Presented on Givinostat for Treatment of ... The analysis examines VLFF alongside efficacy endpoints observed at the end of the study (month 18), including 4SC, time to rise, 6-minute ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02851797

NCT02851797 | Clinical Study to Evaluate the Efficacy and ... The primary objective of the study was to establish the effects of givinostat versus placebo administered chronically over 18 months to slow disease progression ...

4. cureduchenne.org cureduchenne.org/wp-content/uploads/2025/08/ITF-Therapeutics-Announces-Publication-of-Positive-Long-FINAL.pdf

Company Announcement New data published in Annals of Clinical and Translational Neurology show that long- term treatment with givinostat can significantly delay ...

5. checkrare.com checkrare.com/new-data-on-the-use-of-givinostat-for-treatment-of-patients-with-duchenne-muscular-dystrophy/

New Data on the Use of Givinostat for Treatment of Patients ... These results were favorable for givinostat over placebo in all 3 doses. Characterizing Thrombocytopenia in Patients with Duchenne Muscular ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/217865Orig1s000lbl.pdf

DUVYZAT (givinostat) oral suspension - accessdata.fda.gov The safety profile of DUVYZAT is based on a double-blind, placebo-controlled, 18-month study in a total of 179 ambulant DMD patients aged 6 years or older on ...

7. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/duvyzat

Duvyzat | European Medicines Agency (EMA) Duvyzat is a medicine used to treat people aged 6 years and older with Duchenne muscular dystrophy who are able to walk and are already being treated with ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05933057

Study Details | NCT05933057 | Efficacy, Safety and ... This study will evaluate the efficacy, safety, and tolerability of givinostat in non-ambulant patients to further corroborate data from the completed phase 3 ...

9. medcentral.com medcentral.com/drugs/monograph/188877-324017/givinostat-oral

Givinostat: uses, dosing, warnings, adverse events, ... Givinostat hydrochloride is used for the treatment of Duchenne muscular dystrophy (DMD) ... Safety and efficacy of givinostat in boys with Duchenne muscular ...

10. parentprojectmd.org parentprojectmd.org/italfarmaco-addresses-patient-deaths-duvyzat-safety-profile-in-community-letter/

Italfarmaco Addresses Patient Deaths, DUVYZAT Safety ... DUVYZAT was approved by the U.S. Food and Drug Administration (FDA) in March 2024 for individuals 6 years and older living with Duchenne.