Study to evaluate the micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of givinostat in patients with Becker Muscular Dystrophy

• Register: EUCTR
• Last refreshed on: 25 May 2021
• Main ID: EUCTR2017-001629-41-NL
• Date of registration: 31/05/2018
• Prospective Registration: Yes
• Primary sponsor: ITALFARMACO S.P.A.
• Public title: Study to evaluate the micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of givinostat in patients with Becker Muscular Dystrophy
• Scientific title: A randomised, double-blind, placebo-controlled study to evaluate the micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of givinostat in patients with Becker Muscular Dystrophy - NA
• Date of first enrolment: 15/11/2018
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001629-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy, Netherlands

Contacts

• Name: Clinical Research and Development
• Affiliation: ITALFARMACO S.P.A.

• Name: Clinical Research and Development
• Affiliation: ITALFARMACO S.P.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ambulant male patients aged =18 years to < 65 years at randomization with BMD diagnosis confirmed by genetic testing.
2. Able and willing to give informed consent in writing.
3. Able to perform 6MWT at screening with a minimum distance of 200 m and maximum distance of 450 m.
4. If in treatment with systemic corticosteroids and/or ACE inhibitor, and/or ß or a adrenergic receptor blocker, no significant
change in dosage or dosing regimen (excluding changes related to body weight change) for a minimum of 6 months immediately
prior to start of study treatment.
5. Patients must be willing to use adequate contraception. Contraceptive methods must be used from Randomization through 3
months after the last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 48
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Exposure to another investigational drug within 3 months prior to the start of study treatment.
2. Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength or function within
3 months prior to the start of study treatment (e.g., growth hormone). Vitamin D, calcium, and any other supplements will be
allowed.
3. Surgery that might affect muscle strength or function within 3 months before study entry or planned surgery at any time during
the study.
4. Presence of other clinically significant disease that in the Investigator’s opinion could adversely affect the safety of the patient,
making it unlikely that the course of treatment or follow-up is completed, or could impair the assessment of study results.
5. A diagnosis of other uncontrolled neurological diseases or presence of relevant somatic disorders not related to BMD that may interfere with the ability to perform the muscle function tests and/or to comply with the study protocol procedures.
6. Platelet count, WBC count and hemoglobin at screening < Lower Limit of Normal (LLN). If laboratory screening results are < LLN,
platelet count, WBC count and hemoglobin are to be repeated once, and if again < LLN become exclusionary.
7. Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction <
50% at screening or with heart transplant.
8. Current liver disease or impairment, including but not limited to elevated total bilirubin (> 1.5 x ULN), unless secondary to
Gilbert’s disease or pattern consistent with Gilbert's disease.
9. Inadequate renal function, as defined by serum Cystatin C > 2 x the upper limit of normal (ULN). If the value is > 2 x ULN,
serum Cystatin C will be repeated once, and if again > 2 x ULN becomes exclusionary.
10. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening.
11. Baseline corrected QT interval, Fredericia’s correction (QTcF) > 450 msec, (as the mean of 3 consecutive readings 5 minutes
apart) or history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT
syndrome).
12. Current psychiatric illness/social situations rendering the potential patient unable to understand and comply with the muscle function
tests and/or with the study protocol procedures.
13. Hypersensitivity to the components of study medication.
14. Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose intolerance.
15. Contraindications to muscle biopsy.
16. Contraindications to MRI/MRS (e.g., claustrophobia, metal implants, or seizure disorder).
17. Hypertriglyceridemia (> 1.5 x upper limit of normal [ULN])*
* At screening, patients with hypertriglyceridemia can be enrolled if in stable treatment and with controlled levels of triglycerides (i.e. within normal range) for at least six months.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Distrofia Muscolare di Becker (DMB)
MedDRA version: 20.0 Level: PT Classification code 10059117 Term: Becker's muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Givinostat (hydrochloride monohydrate)
Product Code: ITF2357
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Givinostat (hydrochloride monohydrate)
CAS Number: 732302-99-7
Current Sponsor code: ITF2357
Other descriptive name: GIVINOSTAT
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To establish the histological effects of givinostat versus placebo administered over 12 months.

Timepoint(s) of evaluation of this end point: Before and after 12 months of treatment with givinostat versus placebo

Primary end point(s): Mean change in mean Cross Sectional Area (CSA) comparing the histology of muscle biopsies

Secondary Objective: To establish the macroscopic muscle effects of givinostat versus placebo administered chronically over 12 months assessed by MRI/MRS.
• To establish the other histological effects of givinostat versus placebo administered over 12 months.
• To establish the efficacy of givinostat versus placebo administered chronically over 12 months in slowing disease progression.
• To assess the safety and tolerability of givinostat versus placebo administered chronically.
• To evaluate the pharmacokinetic (PK) profile of givinostat administered chronically in the target population.
• To evaluate the impact of givinostat versus placebo administered chronically on quality of life and activities of daily living.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Before and after 12 months of treatment with givinostat versus placebo;
2. Before and after 12 months of treatment with givinostat versus placebo;
3. Before and after 12 months of treatment with givinostat versus placebo;
4. Before and after 12 months of treatment with givinostat;
5. Before and after 12 months of treatment with givinostat versus placebo;
6. Before and after 12 months of treatment with givinostat versus placebo;
7. Before and after 12 months of treatment with givinostat versus placebo;
8. At the end of study;
9. Baseline through end of study;
10. During the study;
11. Before and after 12 months of treatment with givinostat versus placebo;
12. Before and after 12 months of treatment with givinostat as compared to placebo;

Secondary end point(s): 1. Mean change in fat fraction of vastus lateralis and soleus comparing Magnetic Resonance Spectroscopy (MRS);
2. Mean change in fat fraction of pelvic girdle and lower limb muscles comparing Magnetic Resonance Imaging (MRI);
3 .Mean CSA of pelvic girdle and lower limb muscles comparing MRI;
4. Mean change in other histology parameters (e.g. MFA%, % of total fibrosis, regenerative fibers) comparing the histology biopsies;
5. Mean change in Motor Function Measurement (MFM);
6. Mean change in Time Function Tests (time to climb four standard steps, time to rise from floor and time to walk/run 10 m);
7. Mean change in 6 Minute Walking Test (6MWT);
8. Proportion of patients with < 10% worsening in 6MWT;
9. Proportion of patients who lose the ability to rise from floor;
10. Proportion of patients who lose ambulation;
11. Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM);
12. Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36]);

Secondary ID(s)

DSC/15/2357/53

Source(s) of Monetary Support

ITALFARMACO S.P.A.

Ethics review

Status: Approved
Approval date: 15/11/2018
Contact: