A Study to Assess Safety/Tolerability, pk, Effects on Histology, Clinical Parameters of Givinostat in Children With DMD
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ClinicalTrials.gov Identifier: NCT01761292 |
Recruitment Status :
Completed
First Posted : January 4, 2013
Results First Posted : June 23, 2020
Last Update Posted : November 7, 2023
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Tracking Information | ||||
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First Submitted Date ICMJE | December 20, 2012 | |||
First Posted Date ICMJE | January 4, 2013 | |||
Results First Submitted Date ICMJE | January 27, 2020 | |||
Results First Posted Date ICMJE | June 23, 2020 | |||
Last Update Posted Date | November 7, 2023 | |||
Study Start Date ICMJE | April 2013 | |||
Actual Primary Completion Date | December 2014 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Change From Baseline to Part 2 in the Value of Muscle Fiber Area (MFA) % Comparing the Histology Biopsies Before and After 12 Months of Treatment With Givinostat. [ Time Frame: After12 months of treatment ] The primary endpoint was the change in histology comparing the brachial biceps biopsies before and after ≥12 months of treatment with Givinostat.
Muscle biopsies: A first brachial biceps biopsy (baseline) was taken prior to the first dose of study drug. A second brachial biceps biopsy was taken at Visit 10 (12 months) from the opposite arm.
The muscle biopsy samples from the biceps muscle were collected by open biopsy. The minimum amount of muscle tissue required was a piece of muscle of at least 0.5 × 0.5 × 0.5 cm.
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Original Primary Outcome Measures ICMJE |
Change in the value of MFA% comparing the histology biopsies before and after 12 months of treatment with Givinostat. [ Time Frame: baseline and 12 months ] | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures |
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Descriptive Information | ||||
Brief Title ICMJE | A Study to Assess Safety/Tolerability, pk, Effects on Histology, Clinical Parameters of Givinostat in Children With DMD | |||
Official Title ICMJE | A Two-Part Study to Assess the Safety and Tolerability, Pharmacokinetics, and Effects on Histology and Different Clinical Parameters of Givinostat in Ambulant Children With Duchenne Muscular Dystrophy | |||
Brief Summary | The primary objective of Parts 1 and 2 of the study were to establish the histologic effects of givinostat administered chronically at the selected daily dose. The secondary objectives of Parts 1 and 2 of the study were as follows:
The primary objective of the Extension of the study was to evaluate the safety and tolerability of long-term administration of givinostat administered chronically at the selected daily dose in children with DMD. The secondary objectives of the Extensions were:
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Detailed Description | This is a 2-part, phase II study to assess the effects of Givinostat on muscle histologic parameters and on clinical parameters in ambulant children with DMD. The safety, tolerability, and pharmacokinetics of Givinostat will also be assessed. Approximately 20 children were to be enrolled in the study as follows: the first 4 children were to be treated at a low dose level of givinostat (25 mg twice daily [BID] in children who weighed 20 kg to 49 kg and 37.5 mg BID in children who weighed ≥ 50 kg). If none of the stopping criteria were met after 2 weeks of treatment at the low dose, the review team was to determine the escalated dose level (ie, intermediate dose level) to be used for the treatment of an additional 8 children who were to be treated at the intermediate dose. The 4 children previously treated at the low dose level were also switched to the intermediate dose level. If none of the stopping criteria were met after 2 weeks of treatment at the intermediate dose, the review team was to determine the subsequent escalated dose level to be used for the treatment of an additional 8 children who were to be treated at the high dose. All children treated at the intermediate dose level were to be switched to the high dose level. Once all 20 children enrolled during Part 1 of the study had been treated for at least 2 weeks, the review team was to determine the recommended dose (RD) to be used in Part 2 based on the safety and tolerability profile observed and on the pharmacokinetic (PK) analyses. All the children enrolled were switched to the RD level (37.5 mg BID), which was administered for the subsequent 12 months of the study (Part 2). At the end of Part 2 of the study, parents were asked to consent and patients to assent to continuing their participation in the Extension to receive the study treatment at least until the final analysis was performed (Part 3-Extensions; after 52 months of treatment). The patients received givinostat at the same ongoing dose, during the last visit planned at 12 months, and were treated for additional 40 months (Extensions 1, 2, and 3 up to month 52). |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Duchenne Muscular Dystrophy (DMD) | |||
Intervention ICMJE | Drug: Givinostat
Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, administered orally under fed conditions at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1 for two weeks, and 25 mg BID and 37.5 mg BID during Part 2 for 12 months. Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID or 37.5 mg BID during Extension 1, and modified as per patient's weight during Extensions 2 and 3 (up to 52 months).
Other Name: ITF2357
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Study Arms ICMJE | Experimental: Givinostat
Givinostat will be administered as 2 oral doses daily while the child is in fed state.
Intervention: Drug: Givinostat
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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. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
20 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Actual Study Completion Date ICMJE | November 2017 | |||
Actual Primary Completion Date | December 2014 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 7 Years to 11 Years (Child) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Italy | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01761292 | |||
Other Study ID Numbers ICMJE | DSC/11/2357/43 2012-002566-12 ( EudraCT Number ) |
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Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Italfarmaco | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Italfarmaco | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Italfarmaco | |||
Verification Date | June 2020 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |