Givinostat for Duchenne Muscular Dystrophy

(ULYSSES Trial)

Recruiting at 24 trial locations

Overseen By Italfarmaco Patient Advocacy

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Italfarmaco

Must be taking: Corticosteroids

Must not be taking: Dystrophin restoration, Gene therapy

Disqualifiers: Respiratory failure, Cardiomyopathy, Liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 4

Duration: 72 weeks

138 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called givinostat for boys with Duchenne Muscular Dystrophy (DMD) who use a wheelchair. The goal is to determine the safety and effectiveness of givinostat in improving health outcomes for those unable to walk due to DMD. Participants will receive either the actual treatment or a placebo (a non-active substance) alongside their regular medication for 18 months. Boys diagnosed with DMD, who use a wheelchair, and have stable medication routines might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that if you are on medication for DMD-associated heart issues, it must be stable for at least 1 month before starting the study. If you are on corticosteroids, they must be stable for at least 6 months. Other medications that might affect muscle strength or function should not have been used within 3 months before starting the study.

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

Research shows that givinostat has been studied for use in Duchenne Muscular Dystrophy (DMD) and is approved by the FDA for individuals aged 6 and older with this condition. In earlier studies with ambulatory patients, givinostat was generally well-tolerated, with mostly mild to moderate side effects reported.

Long-term studies suggest that givinostat can help slow the progression of DMD. This ongoing research enhances understanding of the treatment's safety and effectiveness over time.

Although givinostat is now approved for use, the current trial focuses on non-ambulatory patients. The researchers are still assessing its safety in this specific group. Overall, previous research provides a solid basis for its safety, but individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Duchenne Muscular Dystrophy?

Givinostat is unique because it targets the inflammatory processes that contribute to muscle degeneration in Duchenne Muscular Dystrophy (DMD). While standard treatments typically focus on managing symptoms with corticosteroids, Givinostat works by inhibiting histone deacetylases (HDACs), which play a role in muscle repair and inflammation. This different mechanism of action offers the potential for not just slowing muscle damage but also promoting muscle regeneration. Researchers are excited about Givinostat because it could provide a more comprehensive approach to treating DMD, potentially improving both muscle function and 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 may receive, may help slow down Duchenne Muscular Dystrophy (DMD). Studies have found that it can delay important stages of the disease in patients. After 18 months of treatment, patients who took givinostat showed improvements compared to those who took a placebo. This suggests that givinostat could help maintain muscle function longer. The medication's effects were positive in various ways, indicating it may offer significant benefits for people with DMD. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for non-ambulant male children and teens aged 9 to <18 with Duchenne Muscular Dystrophy (DMD). They must have a genetic diagnosis of DMD, be unable to walk or run 10 meters in under 30 seconds without help, and have been on stable corticosteroid treatment for at least 6 months. Participants need parental consent and agree to use contraception during the study.

Inclusion Criteria

Able to give informed assent and/or consent in writing signed by the patient and/or parent/legal guardian

I have been on a stable dose of corticosteroids for at least 6 months.

My arm and hand abilities score is between 3 to 6.

Exclusion Criteria

Exposure to another investigational drug within 3 months prior to start of study treatment

My kidneys are not working well.

I use testosterone only for delayed puberty treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Baseline

Randomisation is performed

1 day

1 visit (in-person)

Treatment

Participants receive either givinostat or placebo for 18 months

72 weeks

Regular visits (in-person)

End of Study

End of study visit at Week 72, offering enrolment in the long-term safety study

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Givinostat

Trial Overview The trial tests Givinostat's effectiveness, safety, and tolerability against a placebo in patients who can't walk due to DMD. It's randomized and double-blind, meaning neither doctors nor participants know who gets the real drug or placebo. The treatment lasts for 18 months with follow-ups.

How Is the Trial Designed?

Group I: Givinostat Experimental Treatment 1 Intervention

Patients will receive concomitant corticosteroid treatment as part of the standard of care.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive concomitant corticosteroid treatment as part of the standard of care.

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+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

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 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]

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, 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]

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]

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. 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.

7. ema.europa.eu ema.europa.eu/en/documents/rmp/duvyzat-epar-risk-management-plan_en.pdf

Duvyzat , INN-givinostat - EMA ... data regarding the efficacy and safety of givinostat in ambulant patients with Duchenne Muscular. Dystrophy in combination with the EPIDYS study results (Meta- ...