GIVINOSTAT for Duchenne muscular dystrophy

Inclusion criteria

• {"criterion_text":"- CORE PHASE: Male children aged ≥2 to <6 years at screening (subjects ≥6 years of age at screening will not be enrolled into the study)"}
• {"criterion_text":"- CORE PHASE: Written consent provided by parent/legal guardian and subject written assent, if applicable (according to local regulation)"}
• {"criterion_text":"- CORE PHASE: A genetic diagnosis of DMD"}
• {"criterion_text":"- CORE PHASE: Corticosteroid treatment considerations: a.\tFor subjects receiving a stable dose of oral systemic corticosteroids: No significant change in dose or dosing regimen (except for adjustments due to body weight change) for a minimum of 3 months immediately prior to the start of study drug or b.\tFor subjects without current corticosteroids treatment: Must not start corticosteroids during core phase (ie, first 48 weeks)"}
• {"criterion_text":"- EXTENSION PHASE: Must have participated in the Core Phase study (48 weeks) and have attended the End of Treatment Visit (EOT/V12)"}
• {"criterion_text":"- EXTENSION PHASE: Give informed consent and /or assent in writing signed by the parent/legal guardian and/or subject (according to local regulation)"}
• {"criterion_text":"- EXTENSION PHASE: In stable oral systemic corticosteroids treatment with no significant change in dose or dosing regimen (except for adjustments due to body weight change). For subjects without corticosteroids during the Core Phase, the treatment can be started based on the Investigator’s clinical medical judgement."}

Exclusion criteria

• {"criterion_text":"- CORE PHASE: Exposure to any other investigational drug within 3 months prior to the start of study drug"}
• {"criterion_text":"- EXTENSION PHASE: Current liver disease or impairment, including but not limited to an elevated total bilirubin (ie, >1.5 × ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert disease"}
• {"criterion_text":"- EXTENSION PHASE: Inadequate renal function, as defined by serum Cystatin C result >2 × ULN"}
• {"criterion_text":"- CORE PHASE: Exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study drug"}
• {"criterion_text":"- EXTENSION PHASE: Fasting triglycerides >300 mg/dL (3.42 mmol/L)"}
• {"criterion_text":"- EXTENSION PHASE: 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":"- EXTENSION PHASE: Evidence of psychiatric illness or social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on the Investigator’s clinical medical judgement"}
• {"criterion_text":"- CORE PHASE: Received any gene therapy (eg, Adeno-associated viruses Micro dystrophin delivery) within 12 months prior to the start of study drug"}
• {"criterion_text":"- CORE PHASE: Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to the start of study drug (eg, growth hormone)"}
• {"criterion_text":"- CORE PHASE: Have had surgery that might have an effect on muscle strength or function within 3 months prior to the start of the study drug or planned surgery at any time during the study"}
• {"criterion_text":"- CORE PHASE: The presence of other clinically significant disease, which, in the Investigator’s opinion, could adversely affect subject’s safety, making it unlikely to complete the study or to be compliant with study-specific requirements that could impair the assessment of study results"}
• {"criterion_text":"- CORE PHASE: 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 subject will be excluded)"}
• {"criterion_text":"- CORE PHASE: Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on the Investigator's clinical medical judgement"}
• {"criterion_text":"- CORE PHASE: Platelet count, white blood cells, and/or haemoglobin < lower limit of normal (LLN) at screening (Note: for abnormal screening laboratory test results ["}
• {"criterion_text":"- CORE PHASE: 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"}
• {"criterion_text":"- CORE PHASE: Body weight <10 kg at screening"}
• {"criterion_text":"- CORE PHASE: 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 in fasting condition, the subject should be excluded)"}
• {"criterion_text":"- CORE PHASE: Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening"}
• {"criterion_text":"- CORE PHASE: Baseline corrected QT interval using Fredericia’s formula (QTcF) >450 msec (as the mean of 3 consecutive readings taken 5 minutes apart) or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome)"}
• {"criterion_text":"- CORE PHASE: Psychiatric illness or social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on the Investigator’s clinical medical judgement"}
• {"criterion_text":"- CORE PHASE: Hypersensitivity to any component of the study drug"}
• {"criterion_text":"- CORE PHASE: Sorbitol intolerance or malabsorption, or have the hereditary form of fructose intolerance"}
• {"criterion_text":"- EXTENSION PHASE: Platelet count, white blood cells, and/or haemoglobin < LLN at EOT/V12"}

Primary endpoints

• {"endpoint_text":"- CORE PHASE: Area under the concentration-time curve from dosing (time 0) to time t at steady state (AUC0-T,ss) after at least 7 days of dosing (at Week 1 and at 6 months) CORE PHASE: Maximum plasma concentration at steady state (Cmax,ss) after at least 7 days of dosing (at Week 1 and at 6 months) CORE PHASE: Elimination half life (t1/2) assessed after at least 7 days of dosing dosing (at Week 1 and at 6 months)","definition_or_measurement_approach":"PK parameters measured at steady state after at least 7 days of dosing; assessments scheduled at Week 1 and at 6 months (AUC0-T,ss, Cmax,ss, t1/2)."}
• {"endpoint_text":"- EXTENSION PHASE: •\tType, incidence, and severity of TEAEs and SAEs from baseline up to Week 144 •\tProportion of subjects experiencing TEAEs from baseline to Week 144","definition_or_measurement_approach":"Safety monitoring of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) from baseline through Week 144; calculation of incidence, severity and proportion of subjects with TEAEs."}

Secondary endpoints

• {"endpoint_text":"- CORE PHASE: •\tType, incidence, and severity of treatment-emergent adverse events (TEAEs) and SAEs from baseline to Week 48 •\tProportion of subjects experiencing TEAEs from baseline to Week 48 •\tChange from baseline vital signs and clinical laboratory tests to each postbaseline visit up to Week 48 •\tChange from baseline electrocardiogram (ECG) to each postbaseline visit up to Week 48","definition_or_measurement_approach":"Safety parameters (TEAEs/SAEs incidence and proportion), changes in vital signs, laboratory tests, and ECG compared to baseline through Week 48."}
• {"endpoint_text":"- CORE PHASE: •\tChange in physical function as per the Bayley III Gross Motor scale from baseline to Week 48 for subjects aged ≥2 to <3.5 years of age •\tChange in physical function as per the North Star Ambulatory Assessment (NSAA) total score from baseline to Week 48 for subjects aged ≥3.5 years of age","definition_or_measurement_approach":"Functional assessments: Bayley III Gross Motor scale for subjects ≥2 to <3.5 years, NSAA total score for subjects ≥3.5 years; change from baseline to Week 48."}
• {"endpoint_text":"- CORE PHASE: •\tChange in Paediatric Outcomes Data Collection Instrument (PODCI) from baseline to Week 48 for subjects aged ≥4 years of age in Cohort 1 only","definition_or_measurement_approach":"Change from baseline in PODCI for Cohort 1 subjects aged ≥4 years measured at Week 48."}
• {"endpoint_text":"- EXTENSION PHASE: •\tType, incidence, and severity of TEAEs and SAEs from baseline up to Week 144 •\tProportion of patients experiencing TEAEs from baseline to Week 144 •\tChange from baseline vital signs and clinical laboratory tests to each postbaseline visit up to Week 144 •\tChange from baseline ECG to each postbaseline up to Week 144","definition_or_measurement_approach":"Long-term safety monitoring through Week 144 including TEAEs/SAEs, vital signs, labs and ECG changes from baseline."}

Belgium

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

24

Number Of Sites

1

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

13-09-2024

Latest Decision Or Authorization Date

11-10-2024

Processing Time Days

28

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

03-07-2024

Latest Decision Or Authorization Date

21-11-2024

Processing Time Days

141

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

Italfarmaco S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Fortrea Inc.

Responsibilities

[{"id":577577,"code":"1"},{"id":577578,"code":"11"},{"id":577579,"code":"12"},{"id":577580,"code":"13"},{"id":577581,"code":"14"},{"id":577582,"code":"2"},{"id":577583,"code":"4"},{"id":577584,"code":"5"}]

Name

Syneos Health Clinique Inc.

Responsibilities

[{"id":577589,"code":"4"}]

Third parties

• {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"[{\"id\":577588,\"code\":\"6\"}]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Alira Health","duties_or_roles":"[{\"id\":577586,\"code\":\"10\"},{\"id\":577587,\"code\":\"6\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"[{\"id\":577589,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"[{\"id\":577577,\"code\":\"1\"},{\"id\":577578,\"code\":\"11\"},{\"id\":577579,\"code\":\"12\"},{\"id\":577580,\"code\":\"13\"},{\"id\":577581,\"code\":\"14\"},{\"id\":577582,\"code\":\"2\"},{\"id\":577583,\"code\":\"4\"},{\"id\":577584,\"code\":\"5\"}]","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Blueprint Genetics Oy","duties_or_roles":"[{\"id\":577585,\"code\":\"4\"}]","organisation_type":"Hospital/Clinic/Other health care facility"}