A 2-Part Study to Assess the Safety and Tolerability, pk, Effects on Histology and Some Clinical Parameters of Givinostat in Ambulant Children With DMD
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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|
- 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 in additional histological endpoints (i.e., cross-sectional area, inflammation, necrosis, fibrosis, and muscle regeneration) after 12 months of treatment with Givinostat at the selected daily dose [ Time Frame: baseline and 12 months ]
- Change in muscular function after 12 months of treatment with Givinostat at the selected daily dose based on the 6MWT, NSAA and PUL [ Time Frame: baseline and 12 months ]
- Type, incidence, and severity of treatment-emergent AEs and SAEs correlated with dose [ Time Frame: baseline and 12 months ]
- Individual Givinostat concentrations tabulated by dose cohort along with descriptive statistics for Part 1 and tabulated along with descriptive statistic for Part 2. [ Time Frame: baseline and 12 months ]
- Change in muscle, fat and fibrosis content after treatment with Givinostat as measured by MRI [ Time Frame: baseline and 12 months ]
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||August 2017|
|Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Givinostat will be administered as 2 oral doses daily while the child is in fed state.
Approximately 20 children will be enrolled in the study as follows: the first 4 children will be treated at a low dose level of Givinostat.
If none of the stopping criteria described in the study protocol are met after 2 weeks of treatment at the low dose, the review team will determine the escalated dose level (i.e., intermediate dose level) to be used for the treatment of an additional 8 children who will be treated at the intermediate dose. The 4 children previously treated at the low dose level will also be switched to the intermediate dose level.
If none of the stopping criteria are met after 2 weeks of treatment at the intermediate dose, the review team will determine the subsequent escalated dose level to be used for the treatment of an additional 8 children who will be treated at the high dose. All children treated at the intermediate dose level will be switched to the high dose level.
Once all 20 children enrolled during the Part 1 of the study have been treated for at least 2 weeks, the review team will 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 will switch to the RD level, which will be administered for the subsequent 12 months of the study (Part 2).
The additional children (if any) will be enrolled during Part 2 of the study and will receive the RD of Givinostat for 12 months.
The total duration of the study is 15 months and an additional 12 months for the extension phase.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01761292
|Azienda Ospedaliera Universitaria Policlinico G. Martino|
|Messina, Italy, 98125|
|IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano|
|Milano, Italy, 20122|
|Policlinico Agostino Gemelli|
|Roma, Italy, 00168|
|Ospedale Pediatrico Bambino Gesù|
|Rome, Italy, 00165|