Ignite Creation Date:
2024-05-06 @ 1:15 AM
Last Modification Date:
2024-10-26 @ 11:01 AM
Study NCT ID:
NCT01761292
Status:
COMPLETED
Last Update Posted:
2023-11-07
First Post:
2012-12-20
Brief Title:
A Study to Assess SafetyTolerability pk Effects on Histology Clinical Parameters of Givinostat in Children With DMD
Sponsor:
Italfarmaco
Organization:
Italfarmaco
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2020-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
To establish the effects of givinostat administered chronically at the selected daily dose on functional parameters such as the 6-Minute Walk Test 6MWT North Star Ambulatory Assessment NSAA and performance of upper limb PUL
To establish the safety and tolerability of givinostat administered chronically at the selected daily dose in children with Duchenne muscular dystrophy DMD
To explore the effects of givinostat administered chronically at the selected daily dose on parameters such as magnetic resonance imaging MRI and biomarkers
To explore the acceptabilitypalatability of the oral suspension
To explore whether the effects of givinostat on disease progression may be related to the type of DMD mutation
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
To establish the effects of givinostat administered chronically at the selected daily dose on muscular functional parameters such as the 6MWT NSAA and PUL Extensions 1 2 and 3
To explore the effects of givinostat administered chronically at the selected daily dose on parameters such as MRI Extension 1
To collect information related to 2 biomarkers latent Transforming growth factor β TGFβ binding protein 4 LTBP4 and osteopontin genotype at the beginning of Extension 2 only
To collect information related to time to wheelchair and how much time the children spend in wheelchair Extension 3 - only for the children who were not able to complete the 6MWT
The secondary objectives of Parts 1 and 2 of the study were as follows
To establish the effects of givinostat administered chronically at the selected daily dose on functional parameters such as the 6-Minute Walk Test 6MWT North Star Ambulatory Assessment NSAA and performance of upper limb PUL
To establish the safety and tolerability of givinostat administered chronically at the selected daily dose in children with Duchenne muscular dystrophy DMD
To explore the effects of givinostat administered chronically at the selected daily dose on parameters such as magnetic resonance imaging MRI and biomarkers
To explore the acceptabilitypalatability of the oral suspension
To explore whether the effects of givinostat on disease progression may be related to the type of DMD mutation
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
To establish the effects of givinostat administered chronically at the selected daily dose on muscular functional parameters such as the 6MWT NSAA and PUL Extensions 1 2 and 3
To explore the effects of givinostat administered chronically at the selected daily dose on parameters such as MRI Extension 1
To collect information related to 2 biomarkers latent Transforming growth factor β TGFβ binding protein 4 LTBP4 and osteopontin genotype at the beginning of Extension 2 only
To collect information related to time to wheelchair and how much time the children spend in wheelchair Extension 3 - only for the children who were not able to complete the 6MWT
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 375 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 375 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
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 375 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 375 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2012-002566-12 | EUDRACT_NUMBER | None | None |