What Is Givinostat?
Givinostat is an FDA-approved medication for the treatment of Chronic Myeloproliferative Neoplasms (cMPN), including conditions such as Polycythemia Vera, Essential Thrombocythemia, and Myelofibrosis. While its precise mechanism of action is still under investigation, Givinostat is understood to influence cellular processes that contribute to these conditions.
Beyond its approved uses, Givinostat is also being studied in various clinical trials for other conditions. These investigations aim to assess its safety, tolerability, and efficacy across a broader range of diseases. As of the latest data, a total of 15 trials involving Givinostat have been conducted or are ongoing, with a cumulative enrollment of 1,086 participants. These studies began in 2009, with the latest trial initiated in 2025. All studies for Givinostat are sponsored by Italfarmaco.
Uses and Conditions Under Study
Givinostat is currently being investigated in clinical trials for several conditions, in addition to its approved uses for Chronic Myeloproliferative Neoplasms. These studies explore its potential benefits and gather more information on its effects.
- Muscular Dystrophy: Givinostat is being studied for Duchenne Muscular Dystrophy and Becker Muscular Dystrophy. Duchenne Muscular Dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. A total of 6 trials are exploring Givinostat's role in these conditions, including specific studies for Duchenne Muscular Dystrophy (DMD).
- Myeloproliferative Neoplasms: Beyond its approved uses, Givinostat continues to be investigated for specific myeloproliferative neoplasms, such as Polycythemia Vera and Chronic Myeloproliferative Neoplasms. These conditions involve the overproduction of blood cells in the bone marrow. There are 4 trials focused on these types of blood disorders.
- Juvenile Idiopathic Arthritis: Givinostat is also under investigation for Juvenile Idiopathic Arthritis and Polyarticular Course Juvenile Idiopathic Arthritis. These are types of arthritis that affect children, causing joint pain, swelling, and stiffness. A total of 2 trials are assessing Givinostat's potential in treating these pediatric rheumatic conditions.
- Drug-Drug Interaction Studies: Several trials, totaling 3 studies, are dedicated to understanding how Givinostat interacts with other medications. These drug-drug interaction studies are crucial for determining safe co-administration with other treatments and for understanding its pharmacokinetic profile.
- Healthy Volunteers: One trial involves healthy volunteers. Studies in healthy individuals help researchers understand how the drug is absorbed, distributed, metabolized, and excreted in the body without the confounding factors of a disease state.
Dosing
Givinostat is primarily studied and administered as an oral suspension. The most common strength investigated is 10 mg/mL. The way Givinostat is taken can vary depending on the specific condition being treated and the patient's individual needs, often involving a flexible dose regimen.
Generally, Givinostat is administered twice daily in a fed state. The dosage is typically adjusted based on the patient's weight, and the starting dose may be reduced according to predefined safety rules to manage potential toxicities or to optimize efficacy. Some specific trial protocols have involved once-daily administration on certain days, or twice-daily dosing with particular timing and fasting requirements.
In pediatric studies, Givinostat has been investigated in different age cohorts, including children from 2 to 4 years old and from 4 to 6 years old. Doses such as 1.0 mg/kg daily and 1.5 mg/kg daily have been explored in these younger populations, reflecting a weight-based approach to dosing.
Side Effects
In clinical trials involving 152 patients taking Givinostat, the most common side effects included:
- A decrease in platelet count was reported by 44.7% of patients taking Givinostat, compared to 11.5% of patients on placebo. Thrombocytopenia, a condition of low platelets, was observed in 16.1% of Givinostat patients in one trial (n=118) versus 0% on placebo.
- Diarrhea occurred in 38.8% of patients on Givinostat, compared to 14.1% on placebo.
- Vomiting was experienced by 23.0% of patients taking Givinostat, versus 10.3% on placebo.
- Abdominal pain affected 17.8% of patients on Givinostat, compared to 11.5% on placebo. Upper abdominal pain was reported by 13.2% of Givinostat patients versus 10.3% on placebo.
- High levels of triglycerides in the blood (hypertriglyceridaemia) were seen in 15.8% of patients taking Givinostat, compared to 2.6% on placebo. Increased blood triglycerides were also reported in 11.8% of Givinostat patients versus 5.1% on placebo.
Other side effects, such as nasopharyngitis, headache, fall, and cough, occurred at similar or lower rates in patients taking Givinostat compared to those on placebo, suggesting they may not be directly related to the drug.
Clinical Trial Results
Polycythemia Vera
In a Phase 2 study (NCT00928707) evaluating Givinostat in combination with hydroxyurea for polycythemia vera, patients showed an overall hematological response. At Week 12, approximately 50% of patients achieved an overall hematological response. This response rate was maintained at approximately 50% at Week 24 following dose escalation after Week 12.
Another study (NCT01901432) further investigated Givinostat in patients with polycythemia vera. In Part A of the study, the overall response rate (ORR) was 72.7% after both 3 and 6 cycles of treatment. In Part B, at the maximum tolerated dose of 100 mg twice daily, the ORR was 80.6% after 3 cycles and remained 80.6% after 6 cycles. This included 71.0% of patients achieving a complete response and 9.7% achieving a partial response after 3 cycles.
Juvenile Idiopathic Arthritis (JIA)
Two studies (NCT01261624 and NCT01557452
Currently Recruiting Trials
Several clinical trials for Givinostat are actively recruiting participants, exploring its potential across different conditions and patient populations. These studies aim to gather more information on the drug's effectiveness, safety, and how it is processed by the body.
One ongoing study, NCT06769633, is a Phase 2 trial focused on Duchenne Muscular Dystrophy (DMD) in younger patients. This open-label study is assessing the pharmacokinetics and safety of Givinostat in children aged from at least 2 years to less than 6 years old. It is divided into two cohorts: one for children aged 4 to 6 years, and another for those aged 2 to 4 years. The study plans for a screening period of approximately four weeks, followed by a core treatment duration of about 48 weeks. It aims to enroll 18 participants.
For patients with Polycythemia Vera, a Phase 3 study, NCT06093672, is comparing the efficacy and safety of Givinostat against hydroxyurea. This trial is specifically designed for Jak2V617F-positive high-risk polycythemia vera patients and seeks to enroll 220 participants.
Another Phase 3 trial, NCT05933057, is investigating Givinostat in non-ambulant male pediatric patients with Duchenne Muscular Dystrophy, specifically those aged 9 to less than 18 years. This randomized, double-blind, placebo-controlled study will evaluate the efficacy, safety, and tolerability of Givinostat, with 138 patients being randomized to receive either Givinostat or a placebo.
Finally, the long-term safety and tolerability of Givinostat in Duchenne Muscular Dystrophy patients is being assessed in NCT03373968. This open-label Phase 2/Phase 3 study is for individuals with DMD who have previously participated in other Givinostat studies. It aims to enroll 206 patients to continue monitoring the drug's effects over an extended period.
Where to Participate
Clinical trials for Givinostat are currently being conducted across a broad geographical area, with study sites located in 24 sites across 23 cities and 18 states. This wide reach aims to make participation accessible to a diverse patient population.
Some of the top locations with active sites include:
- Houston, Texas (2 sites)
- Redlands, California (1 site)
- Sacramento, California (1 site)
- San Diego, California (1 site)
- Englewood, Colorado (1 site)
- Hartford, Connecticut (1 site)
- Gainesville, Florida (1 site)
- Atlanta, Georgia (1 site)
- Iowa City, Iowa (1 site)
- Bethesda, Maryland (1 site)
General eligibility criteria for these studies typically include participants aged between 2 and 18 years. All genders are welcome, and the trials are specifically designed for patients with the relevant conditions, meaning healthy volunteers are not being recruited. Children are eligible to participate.
Development Timeline
The journey of Givinostat began with its first clinical trial initiated on June 26, 2009, marking the start of its development by Italfarmaco. Since then, Italfarmaco has consistently sponsored all 15 clinical trials for Givinostat, demonstrating a dedicated commitment to advancing this compound.
Initially, Givinostat's research focused on conditions such as IBS-C and hyperphosphatemia. Over time, the development pipeline significantly expanded, reflecting a growing understanding of its potential therapeutic applications. The program broadened to include studies in areas like Drug-Drug Interaction, Becker Muscular Dystrophy, and Juvenile Idiopathic Arthritis, including its polyarticular course.
A significant focus emerged in Duchenne Muscular Dystrophy (DMD), with several trials dedicated to this severe genetic condition. Additionally, Givinostat has been explored for Chronic Myeloproliferative Neoplasms. The clinical development has progressed through various phases, including Phase 1, Phase 2, and Phase 3 studies, with some trials spanning combined phases like Phase 1/Phase 2 and Phase 2/Phase 3. The latest trial is projected to conclude by January 10, 2025, continuing the ongoing research into its long-term effects and efficacy. Across all studies, Givinostat has aimed to enroll a total of 1,086 participants.