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Duchenne Muscular DystrophyPhase 3ULYSSESNCT05933057

Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy

A Phase 3 study testing Givinostat in people with Duchenne Muscular Dystrophy, run by Italfarmaco at 29 sites in 12 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy, safety, and tolerability of givinostat in non-ambulant male paediatric (aged 9 to <18 years) patients with DMD. 138 patients will be randomised 2:1 to givinostat or placebo and will be treated for 18 months. Read more about this study

Who is it for?
Ages 9 to 17 years, men only
Conditions the study is for
Duchenne Muscular Dystrophy
What is being tested?
Givinostat
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
138 participants
Where
29 sitesin 12 countries
Study dates
19 Feb 2024to Feb 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 to 17 years
  • Men only
  • No healthy volunteers
  • Child

Who may be able to join

  • Patients must satisfy all the following criteria:
  • Children and adolescent males aged ≥ 9 to <18 years at screening (patients ≥ 18 years of age at screening will not be enrolled into the study)
  • Are able to give informed assent and/or consent in writing signed by the patient and/or parent/legal guardian (according to local regulations)
  • A genetic diagnosis of DMD
  • Non-ambulant, defined as being wheelchair bound and:
  • Unable to perform the 10-meter walk/run test (10MWT), or
Show all 15Show fewer
  • Unable to complete the 10MWT in 30 seconds or less, without any support or devices
  • Performance of the Upper Limb test (PUL version 2.0) entry item scores 3 to 6
  • If on medication for DMD-associated cardiomyopathy (eg, ACE inhibitor, β-blocker, diuretics), stable for ≥1 month immediately prior to start of study treatment, if any
  • Stable corticosteroids, defined as:
  • Receiving systemic corticosteroids for a minimum of 6 months immediately prior to start of study treatment
  • No significant change in dose or dosing regimen (except for adjustments due to body weight change) for a minimum of 6 months immediately prior to start of study treatment
  • Willing to use adequate contraception. Effective contraceptive methods must be used from randomisation visit through 3 months after the last dose of study drug, and include the following:
  • True abstinence (ie, absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, post-ovulation, and symptothermal methods) and withdrawal are not acceptable methods of contraception
  • Condom with spermicide and the female partner must use an effective method of contraception, such as an oral, transdermal, injectable or implanted hormonal contraceptive; intrauterine device; bilateral tubal occlusion, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as for example cervical cap with spermicide jelly.

Who cannot join

  • Patients will be excluded from the study if they satisfy any of the following criteria:
  • Exposure to another investigational drug within 3 months prior to start of study treatment.
  • Have exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study treatment
  • Having received any gene therapy (eg, AAV Micro-dystrophin delivery) prior to start of study treatment
  • Use of any pharmacologic treatment or supplement (other than corticosteroids), that might have had an effect on muscle strength or function within 3 months prior to the start of study treatment (eg, growth hormone); vitamin D, calcium and any other supplements will be allowed
  • Use of testosterone, unless used as a replacement therapy for the treatment of delayed puberty. The testosterone dose and regimen should be stable within 6 months prior to the start of study treatment, and circulating testosterone levels should be within the normal ranges for the patient's age
Show all 25Show fewer
  • Elbow-flexion contractures >30° in the dominant arm
  • Inability to perform consistent PUL 2.0 measurement within ±2 points without shoulder domain or within ±3 points with shoulder domain during paired testing at screening
  • Forced Vital Capacity % of predicted <40%
  • Requirement for daytime ventilator assistance (Note: Night ventilator assistance and use of bi-level positive airway pressure therapy is allowed)
  • Episode of respiratory failure within the 8 weeks prior to screening
  • Symptomatic cardiomyopathy or heart failure and/or left ventricular ejection fraction <45%
  • Baseline corrected QT interval using Fredericia's formula (QTcF) >450 msec (as the mean of 3 consecutive readings 5 minutes apart) or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome)
  • Major surgical procedure (including scoliosis surgery) planned within 1 year of the start of study treatment
  • Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, emphysema, recurrent pneumonia that in the opinion of the Investigator might impact respiratory function
  • Platelets, white blood cells, and/or haemoglobin < lower limit of normal (LLN) at screening (Note: for abnormal screening laboratory test results [<LLN], the platelets count, white blood cell, and haemoglobin will be repeated once; if the repeat test result is still <LLN, the patient should be excluded)
  • Fasting triglycerides >300 mg/dL (3.42 mmol/L) at screening (Note: if the value is >300 mg/dL, the triglycerides will be repeated once; if the repeated test result is still >300 mg/dL, the patient should be excluded)
  • Current or history of liver disease or impairment, including but not limited to a baseline elevated total bilirubin (ie, >1.5 × upper limit of normal [ULN]), unless secondary to Gilbert disease or pattern consistent with Gilbert disease
  • Inadequate renal function, as defined by serum Cystatin C result >2 × ULN (Note: if the value is >2 × ULN, the serum Cystatin C will be repeated once; if the repeated test result is still >2 × ULN, the patient should be excluded)
  • Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
  • Hypersensitivity to any component of study medication
  • Sorbitol intolerance or malabsorption, or have the hereditary form of fructose intolerance
  • Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on Investigator judgement
  • Psychiatric illness or social situations rendering the potential patient unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on Investigator judgement
  • Have contraindications to MRI scan (eg, claustrophobia, metal implants, or uncontrolled seizure disorder), based on Investigator's judgement.

Trial locations and contacts

29 sites in 12 countries. Contact the study team or a site near you to ask about taking part.

Italfarmaco Patient Advocacy contact

+39 02 6443 1

patientadvocacy@italfarmacogroup.com

29 sites in 12 countries

Italy5 sites, 5 recruiting

  • Associazione La Nostra Famiglia - IRCCS Eugenio Medea - Bosisio Parini

    Lecco, 23842

    +39031-877111, grazia.dangelo@lanostrafamiglia.it

    Maria Grazia D´Angelo, MD

    Recruiting

  • Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca' Granda - NeuroMuscular Omnicentre

    Milan, 20162

    (+39) 0291433764, crc@centrocliniconemo.it

    Valeria Sansone, MD

    Recruiting

  • Università degli Studi di Padova - Azienda Ospedaliera di Padova

    Padova, 35128

    +39 049 8213622, elena.pegoraro@unipd.it

    luca.bello@unipd.it

    Recruiting

  • Ospedale Pediatrico Bambino Gesù

    Roma, 00165

    +39 06 68592105, adele2.damico@opbg.net

    clinicineuromuscolari@OPBGMAIL.onmicrosoft.com

    Recruiting

  • Policlinico Universitario Agostino Gemelli - Università Cattolica del Sacro Cuore

    Roma, 00165

    +39 0630158576, eugeniomaria.mercuri@policlinicogemelli.it

    Eugenio M Mercuri, MD

    Recruiting

Other trials in Italy

Canada4 sites, 4 recruiting

  • The University of Western Ontario - Children's Health Research Institute

    London, Ontario, N6A 5W9

    +1 519-685-8441, rhiannon.hicks@lhsc.on.ca

    Craig Campbell, MD

    Recruiting

  • University of Ottawa - Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

    +1 613-737-7600 ext. 4017, ehillsmith@cheo.on.ca

    Hugh McMillan, MD

    Recruiting

  • University of Toronto - Holland Bloorview Kids Rehabilitation Hospital

    Toronto, Ontario, M4G 1R8

    neuromuscular.research@hollandbloorview.ca

    Laura McAdam, MD

    Recruiting

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

    604-875-2345 ext. 6549, Nmartic3@cw.bc.ca

    Kathryn Selby, MD

    Recruiting

Other trials in Canada

Germany4 sites, 4 recruiting

  • Charite-Universitaetsmedizin Berlin

    Berlin, 10117

    neuropaed-studie@charite.de

    Joanna Schneider, MD

    Recruiting

  • Universitätsklinikum Essen Kinder-und Jugendmedizin Neuropadiatrie

    Essen, 45147

    Heike Kolbel, MD, +49 201 723 2508, heike.koelbel@uk-essen.de

    Not yet recruiting

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 53113

    +49 (0)76127043000, muskelzentrum@uniklinik-freiburg.de

    Janbernd Kirschner, MD

    Recruiting

  • Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Kinder- und Jugendmedizin

    Hamburg, 20246

    Jessika Johannsen, MD, +49 40 7410 55512, j.johannsen@uke.de

    Not yet recruiting

Other trials in Germany

France3 sites, 3 recruiting

  • Centre Hospitalier Régional Universitaire de Lille

    Lille, 59037

    +33 (3) 20 44 60 58, cicpediatrie@chru-lille.fr

    Jean-Baptiste Davion, MD

    Recruiting

  • Centre hospitalier universitaire - Hôpitaux de Marseille

    Marseille, 13385

    +33 4 91 38 68 17, cecile.halbert@ap-hm.fr

    Cecile Halbert, MD

    Recruiting

  • Hôpital Armand-Trousseau - I-Motion

    Paris, 75935

    +33 1 44 73 65 37, consultation-imotion@institut-myologie.org

    Marina Colella, MD

    Recruiting

Other trials in France

United Kingdom3 sites

  • NHS Greater Glasgow and Clyde - Royal Hospital for Children

    Glasgow, Scotland, G51 4TF

    Active, not recruiting

  • Newcastle upon Tyne Hospitals NHS Foundation Trust - Newcastle University

    Newcastle upon Tyne, England, NE1 3BZ

    Active, not recruiting

  • Oxford University Hospitals NHS Foundation Trust

    Oxford, England, OX3 9DU

    Withdrawn

Other trials in United Kingdom

Netherlands2 sites, 2 recruiting

  • Leids Universitair Medisch Centrum (LUMC)

    Leiden, 2300 RC

    duchenne@lumc.nl

    Erik Niks, MD

    Recruiting

  • Radboud Universitair Medisch Centrum (Radboudumc)

    Nijmegen, 6500 HB

    +31(0)650176591, clinicaltrials.reval@radboudumc.nl

    Saskia Houwen-van Opstal, MD

    Recruiting

Other trials in Netherlands

Poland2 sites, 2 recruiting

  • Uniwersyteckie Centrum Kliniczne, Klinika Neurologii Rozwojowej

    Gdansk, 80952

    Maria Mazurkiewicz-Bełdzińska, MD, +58 349 23 9, mmazur@gumed.edu.pl

    Not yet recruiting

  • Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny

    Warsaw, 02097

    Anna Putulska-Chromik, +48 602 316 301, apotulska@wum.edu.pl

    Not yet recruiting

Other trials in Poland

Spain2 sites, 2 recruiting

  • Hospital Sant Joan de Déu

    Barcelona, 08950

    Carlos Ortez, MD, +34 627 54 84 53, carlos.ortez@sjd.es

    Recruiting

  • Hospital Universitario y Politécnico La Fe

    Valencia, 46026

    Nuria Muelas Gomez, MD, +34 961 24 40 00, muelas_nur@gva.es

    Recruiting

Other trials in Spain

Belgium1 site, 1 recruiting

  • Universitaire Ziekenhuizen Leuven

    Leuven, 3000

    +3216348177, eline.cuveele@uzleuven.be

    Liesbeth De Waele, MD

    Recruiting

Other trials in Belgium

Czechia1 site, 1 recruiting

  • Klinika dětské neurologie 2. LF, Fakultní nemocnice v Motole

    Prague, 15006

    Jana Haberlova, MD, +420 224 433 301, jana.haberlova@fnmotol.cz

    Not yet recruiting

Other trials in Czechia

Serbia1 site, 1 recruiting

  • Clinic of Neurology and Psychiatry for Children and Youth

    Belgrade, 11000

    Dragana Vucinic, MD, +381112658355, dragana.vucinic.npk@gmail.com

    Not yet recruiting

Other trials in Serbia

Sweden1 site, 1 recruiting

  • Karolinska University Hospital, Solna CKB Centrum för Kliniska Barnstudier

    Stockholm, 17176

    Thomas Sejersen, MD, +46851777342, thomas.sejersen@ki.se

    Not yet recruiting

Other trials in Sweden

About this study

Official title: Randomised, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy

This is a randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy, safety, and tolerability of givinostat in non-ambulant male paediatric (aged 9 to <18 years) patients with DMD. 138 patients will be randomised 2:1 to givinostat or placebo and will be treated for 18 months.

  • Planned screening duration: approximately 4 weeks (±14 days)
  • Planned treatment duration: 18 months (approximately 72 weeks)
  • Planned follow-up duration: 4 weeks (±7 days) (for patients not participating in the long-term safety study)
  • Total duration of study participation: up to 83 weeks (ie, 20-21 months)
Read the detailed description

Duchenne muscular dystrophy is a rare, progressive, debilitating and life-threatening condition for which there is a critical need for novel therapies that are effective and well-tolerated in all DMD patients. Steroids are generally recognised as the standard of care in the general DMD population; however, they are not suitable for all patients.

Givinostat, a HDAC inhibitor, was developed for the treatment of DMD based on: (i) the role that increased HDAC activity is thought to exert in contributing to DMD pathogenesis; and (ii) givinostat's ability to counter the pathophysiological and degenerative mechanisms causing muscle insufficiency in boys with DMD.

This study will evaluate the efficacy, safety, and tolerability of givinostat in non-ambulant patients to further corroborate data from the completed phase 3 pivotal study of givinostat in ambulant patients with DMD (ie, Study DSC/14/2357/48, NCT02851797). Primary Objective of the study is to demonstrate the efficacy of givinostat in reducing muscle decline in non-ambulant DMD patients, as measured by Performance of the Upper Limb (PUL) 2.0. Secondary Objectives of the study are to evaluate the safety and tolerability of givinostat in non-ambulant DMD patients, and to further explore the efficacy of givinostat in non-ambulant DMD patients.

A total of 138 patients are planned for enrolment. Patients will be randomised 2:1 to givinostat or placebo and will be treated for 18 months.

The study will be comprised of:

  • A screening period, during which eligibility will be confirmed within 4 weeks (±14 days)
  • A baseline visit, during which randomisation will be performed
  • A double-blind treatment period, during which patients will receive either givinostat or placebo for 18 months (approximately 72 weeks)
  • An end of study visit, occurring at Week 72 (±7 days) at the end of the treatment period. At the end of study visit, all the patients (regardless of treatment arm) will be offered enrolment in the long-term safety study DSC/14/2357/51 (NCT03373968) during which they will receive givinostat.
  • A follow-up visit, for those patients not consenting to participation in the long-term safety study, that will occur 4 weeks after the end of study visit (ie, Week 76 ±7 days).
Being tested
Givinostat, Placebo
Keywords
Duchenne Muscular Dystrophy, givinostat
Medical subject headings
Muscular Dystrophy, Duchenne

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GivinostatDrug

    Also called ITF2357

    Givinostat has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose could be reduced based on predefined safety rules.

  • PlaceboDrug

    Placebo, manufactured to mimic givinostat, has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose could be reduced based on predefined safety rules.

Study groups in NCT05933057
Study groupRoleWhat they receive
GivinostatExperimentalPatients will receive concomitant corticosteroid treatment as part of the standard of care.
Receives: Drug: Givinostat
PlaceboPlacebo comparatorPatients will receive concomitant corticosteroid treatment as part of the standard of care.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change of Performance of Upper Limb 2.0 (PUL) total score at 18 months of treatment of givinostat compared to placebo group.

    The PUL examines 3 major "dimensions" of upper extremity function: shoulder, middle, and distal functions. It includes 22 scored items; a score of 42 (12 for shoulder; 17 for mid-level, and 13 for distal) indicates the highest level of independent function and 0 the lowest.

    Measured: Baseline and 18 months

Secondary outcomes (8)

  1. Change from baseline of Peak Expiratory Flow percent predicted (PEF%p) at 18 months of treatment of givinostat compared to placebo group

    Measured: Baseline and 18 months

  2. Change from baseline of Forced Vital Capacity percent predicted (FVC%p) at 18 months of treatment of givinostat compared to placebo group

    Measured: Baseline and 18 months

  3. Cumulative loss of PUL total score over 18 months of treatment of givinostat compared to placebo group.

    Measured: Baseline to 18 months

  4. Type, incidence, and severity of treatment-emergent adverse events

    Measured: Baseline to 18 months

  5. Proportion of patients experiencing treatment-emergent adverse events

    Measured: Baseline to 18 months

  6. Change from baseline vital signs and clinical laboratory tests

    Measured: Baseline and 18 months

  7. Change from baseline electrocardiogram and echocardiogram

    Measured: Baseline and 18 months

  8. Time to assisted ventilation and rate of respiratory infection including duration, severity of respiratory infection and use of antibiotics, of givinostat compared to placebo group.

    Measured: Baseline to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2023
  2. Study start19 Feb 2024
  3. Primary completionFeb 2028 (estimated)
  4. Study completionFeb 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
138 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05933057
Sponsor's protocol ID
DSC/14/2357/50
Other IDs
2023-503521-19, U1111-1295-1799, 1008441, 277453, 2023
Acronym
ULYSSES
Status last verified
Jul 2026
First submitted
16 Jun 2023
Last updated
24 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bettica P, Petrini S, D'Oria V, D'Amico A, Catteruccia M, Pane M, Sivo S, Magri F, Brajkovic S, Messina S, Vita GL, Gatti B, Moggio M, Puri PL, Rocchetti M, De Nicolao G, Vita G, Comi GP, Bertini E, Mercuri E. Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Oct;26(10):643-649. doi: 10.1016/j.nmd.2016.07.002. Epub 2016 Jul 11.

    PubMed 27566866

  • Consalvi S, Mozzetta C, Bettica P, Germani M, Fiorentini F, Del Bene F, Rocchetti M, Leoni F, Monzani V, Mascagni P, Puri PL, Saccone V. Preclinical studies in the mdx mouse model of duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat. Mol Med. 2013 May 20;19(1):79-87. doi: 10.2119/molmed.2013.00011.

    PubMed 23552722

  • Mercuri E, Vilchez JJ, Boespflug-Tanguy O, Zaidman CM, Mah JK, Goemans N, Muller-Felber W, Niks EH, Schara-Schmidt U, Bertini E, Comi GP, Mathews KD, Servais L, Vandenborne K, Johannsen J, Messina S, Spinty S, McAdam L, Selby K, Byrne B, Laverty CG, Carroll K, Zardi G, Cazzaniga S, Coceani N, Bettica P, McDonald CM; EPIDYS Study Group. Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2024 Apr;23(4):393-403. doi: 10.1016/S1474-4422(24)00036-X.

    PubMed 38508835

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Givinostat in people with Duchenne Muscular Dystrophy, run by Italfarmaco at 29 sites in 12 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Italy, Canada, Germany, France, United Kingdom and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Italfarmaco Patient Advocacy (+39 02 6443 1, patientadvocacy@italfarmacogroup.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change of Performance of Upper Limb 2.0 (PUL) total score at 18 months of treatment of givinostat compared to placebo group. (time frame: Baseline and 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05933057, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.

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