Study in which all the patients take the same investigational drug with the aim of evaluate the long-term safety, tolerability, and efficacy of GIVINOSTAT in all the patients affected with Duchenne Muscolar Dystrophy who have been already treated in one of the GIVINOSTAT studies in the past

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Italfarmaco S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

19 Oct 2017 → ongoing

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ITALFARMACO S.p.A.

External identifiers

EU CT number

2023-504520-26-00

EudraCT number

2017-000397-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

To assess the long-term safety and tolerability of GIVINOSTAT in patients with DMD following core protocols program and with naïve GIVINOSTAT DMD subjects, i.e. subjects screened in study DSC/14/2357/48 who met:
- all the inclusion criteria and none of the exclusion criteria,
and
- never been randomized because the enrollment in the off-target group was completed.

Secondary objectives 3

1. To evaluate the effects of long-term administration of GIVINOSTAT on muscular function and strength;
2. To evaluate the effects of long-term administration of GIVINOSTAT on respiratory function
3. To evaluate the impact on daily activities and quality of life following long-term administration of GIVINOSTAT.

Conditions and MedDRA coding

Duchenne Muscular Dystrophy (DMD)

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000551-PIP04-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subjects 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, had a baseline vastus lateralis muscle fat fraction (VL MFF) assessed by MRS in the range ≤5% or >30%, i.e. included in "off-target" group, never been randomized because the enrollment in the off-target group was completed
2. Subjects aged ≥6 years
3. Subjects are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to local regulations)
4. Subjects must be willing to use adequate contraception: Contraceptive methods must since the previous GIVINOSTAT study through 3 months after the last dose of study drug, and include the following: -True abstinence (absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. -Condom with spermicide and the female partner must use an acceptable method of contraception, such as an oral, transdermal, injectable or implanted steroid-based contraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as for example cervical cap with spermicide jelly.

Exclusion criteria 13

1. Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to be enrolled in this study (e.g., growth hormone); Vitamin D, calcium, and any other supplements will be allowed;
2. Use of any current investigational drug other than Givinostat
3. Have presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results
4. Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD
5. Have platelets count, White Blood Cell and Hemoglobin at screening < Lower Limit of Normal (LLN) (for abnormal screening laboratory test results (
6. Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit* (for abnormal screening laboratory test results (>300mg/dl), the triglycerides will be repeated once; if the repeat test result is still >300mg/dl, then exclusionary
7. Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN) at screening visit. If the value is >2 x ULN, the serum Cystatin C will be repeated once; if the repeated test result is still >2 x ULN, the subject should be excluded);
8. Have heart failure (New York Heart Association Class III or IV)
9. Have a current liver disease or impairment, including but not limited to an elevated total bilirubin(i.e. > 1.5 x ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert's
10. Have a baseline 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)
11. Have a psychiatric illness/social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures
12. Have any hypersensitivity to the components of study medication;
13. Have a sorbitol intolerance or sorbitol malabsorption or have the hereditary form of fructose intolerance

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Type, incidence, and severity of treatment related/not related AEs and SAEs

Secondary endpoints 9

1. For ambulant patients: Change from baseline in physical function as measured by 6MWT, NSAA, Time function tests (e.g. time to rise from floor, time to climb 4-stairs, time to 10m walk) (week 48 and then yearly till the end of the study)
2. For ambulant patients: Change from baseline in muscle strength (e.g. knee extension and elbow flexion) as measured by HHM (week 48 and then yearly till the end of the study)
3. For non-ambulant patients: Change in physical function from baseline in the Egen Klassifikation (EK) score (week 48 and then yearly till the end of the study)
4. For non-ambulant patients: Change in patient and/or parent/caregiver reports of activities of daily living as measured by Barthel Index (week 48 and then yearly till the end of the study)
5. For non-ambulant patients: Change in upper limbs muscle strength (week 48 and then yearly till the end of the study) evaluated by handheld myometry (HHM)
6. For all patients: Change from baseline in physical function as measured by the Performance of Upper Limb (PUL) and MFM (week 48 and then yearly till the end of the study)
7. For all patients: Change from baseline in respiratory function (week 48 and then yearly till the end of the study) (e.g. FVC, FEV1, PEF)
8. For all patients: Change in patient and/or parent/caregiver reports of quality of life as measured by PedsQL for paediatric patients and by SF-36 for adults patients (week 48 and then yearly till the end of the study)
9. For all patients: Age to major disease milestones (e.g. age at loss of ambulation, age at respiratory support needed during the day, age at scoliosis surgery, age at death)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Italfarmaco S.p.A.

Sponsor organisation

Italfarmaco S.p.A.

Address

Via Dei Lavoratori 54

City

Cinisello Balsamo

Postcode

20092

Country

Italy

Scientific contact point

Organisation

Italfarmaco S.p.A.

Contact name

Nicoletta Coceani

Public contact point

Organisation

Italfarmaco S.p.A.

Contact name

Patient Advocacy Representative og Italfarmaco S.p.A

Third parties 16

Locations

6 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 285 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications