GIVINOSTAT for Duchenne muscular dystrophy

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Subjects aged ≥6 years"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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

• {"criterion_text":"- 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;"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Have any hypersensitivity to the components of study medication;"}
• {"criterion_text":"- Have a sorbitol intolerance or sorbitol malabsorption or have the hereditary form of fructose intolerance"}
• {"criterion_text":"- Use of any current investigational drug other than Givinostat"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD"}
• {"criterion_text":"- Have platelets count, White Blood Cell and Hemoglobin at screening < Lower Limit of Normal (LLN) (for abnormal screening laboratory test results ("}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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);"}
• {"criterion_text":"- Have heart failure (New York Heart Association Class III or IV)"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Type, incidence, and severity of treatment related/not related AEs and SAEs","definition_or_measurement_approach":"Recording and reporting of adverse events (AEs) and serious adverse events (SAEs): type, incidence and severity will be collected and summarised for treatment-related and non-treatment-related events."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Measured by six-minute walk test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests at week 48 and annually thereafter; change from baseline is the endpoint."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Muscle strength assessed by handheld myometry (HHM) for specified muscle groups at week 48 and annually; change from baseline recorded."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Egen Klassifikation (EK) score assessed at week 48 and annually; change from baseline is evaluated."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Barthel Index questionnaires completed by patient/parent/caregiver at week 48 and annually; change from baseline reported."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Upper limb muscle strength measured by HHM at week 48 and annually; change from baseline assessed."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Performance of Upper Limb (PUL) and Motor Function Measure (MFM) assessments at week 48 and annually; change from baseline recorded."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Pulmonary function tests (e.g. FVC, FEV1, PEF) at week 48 and annually; change from baseline assessed."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Quality of life measured by PedsQL (paediatric) and SF-36 (adult) at week 48 and annually; change from baseline recorded."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Collection of ages at predefined disease milestones from patient history and follow-up; endpoint is age at those events."}

Methods

• Recruitment primarily from subjects who participated in previous GIVINOSTAT studies and have attended the End of Study Visit
• Recruitment of subjects screened in study DSC/14/2357/48 who met all inclusion criteria and none of the exclusion criteria (including those in the "off-target" group defined by VL MFF ≤5% or >30%)

Netherlands

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

10-03-2025

Processing Time Days

200

Number Of Sites

2

Number Of Participants

24

Belgium

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

13-03-2025

Processing Time Days

203

Number Of Sites

2

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

12-03-2025

Processing Time Days

202

Number Of Sites

4

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

20-06-2025

Processing Time Days

302

Number Of Sites

5

Number Of Participants

13

France

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

03-07-2025

Processing Time Days

315

Number Of Sites

4

Number Of Participants

11

Italy

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

11-07-2025

Processing Time Days

323

Number Of Sites

9

Number Of Participants

58

Primary sponsor

Full Name

Italfarmaco S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

IQVIA Limited

Responsibilities

sponsorDuties codes: 1,11,12,13,5,8

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code: 3

Name

Syneos Health Clinique Inc.

Responsibilities

PK Analysis (code 15; value: PK Analysis)

Name

Certara USA Inc.

Responsibilities

Population PK analysis (code 15; value: Population PK analysis)

Name

Eresearchtechnology Inc.

Responsibilities

ECG analysis/review (code 15; value: ECG analysis/review); code 4

Name

Acm Global Central Laboratory Limited

Responsibilities

Primary/ surrogate endpoint test (code 15; value: Primary/ surrogate endpoint test); code 4

Third parties

• {"country":"United Kingdom","full_name":"Illingworth Research Group Limited","duties_or_roles":"Home Nursing (code 15; value: Home Nursing)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fountayn LLC","duties_or_roles":"sponsorDuties code: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"physioterapist training and evaluation (code 15; value: physioterapist training and evaluation)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: 1,11,12,13,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"Primary/ surrogate endpoint test (code 15; value: Primary/ surrogate endpoint test); code 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Patient Primary Limited","duties_or_roles":"Patient Travel reimbursement (code 15; value: Patient Travel reimbursement)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Qualitymetric Incorporated LLC","duties_or_roles":"SF36 questionnaire and proCore software provider (code 15; value: SF36 questionnaire and proCore software provider)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Trinds LLC","duties_or_roles":"IDMC services provider (code 15; value: IDMC services provider)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Alira Health","duties_or_roles":"codes: 10,6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Interpretation Services (code 15; value: Interpretation Services)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"MFM Aide Aux Familles D'Enfants Handicapes Moteurs","duties_or_roles":"MFM physioterapist training and evaluation (code 15; value: MFM physioterapist training and evaluation)","organisation_type":"Health care"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"Population PK analysis (code 15; value: Population PK analysis)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis/review (code 15; value: ECG analysis/review); code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"PK Analysis (code 15; value: PK Analysis)","organisation_type":"Hospital/Clinic/Other health care facility"}