Phase 2
Completed N=20
A Study to Assess Safety/Tolerability, pk, Effects on Histology, Clinical Parameters of Givinostat in Children With DMD
Duchenne Muscular Dystrophy (DMD)
Source: ClinicalTrials.gov NCT01761292 ↗
Enrolled (actual)
20
Serious AEs
14.9%
Results posted
Jun 2020
Primary outcomePrimary: 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. — 12.76 percentage change — p=<0.0001
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 acceptability/palatability 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)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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. |
12.76 | <0.0001 sig |
| SECONDARY Change From Baseline to End of Study in Cross Sectional Area (CSA) |
865.269 | < 0.0001 sig |
| SECONDARY Change From Baseline to End of Study in Fibrosis, Necrosis, Fatty Replacement |
-12.640; -7.585; -5.056; -0.302; -0.964 | — |
| SECONDARY Change From Baseline to End of Study in Number of Hypercontracted Fibers |
-1.204 | — |
| SECONDARY Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test |
-24.6 | — |
| SECONDARY Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) |
-2.8 | — |
| SECONDARY Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) |
-0.2 | — |
| SECONDARY Change From Baseline in Muscular Function After After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test |
-80.0; -127.0; -287.8 | — |
| SECONDARY Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA) |
-5.2; -7.4; -15.2 | — |
| SECONDARY Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL) |
-0.2; -0.2; -4.4 | — |
| SECONDARY Number of Children Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Type and Severity of TEAEs |
20; 20; 20; 16; 9; 1 | — |
Eligibility Criteria
Inclusion Criteria
- Male children aged 7 to 2 x the upper limit of normal.
- Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
- A baseline QTc >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, family history of long QT syndrome).
- Psychiatric illness/social situations rendering the potential child unable to understand and comply with the study protocol.
Data sourced from ClinicalTrials.gov (NCT01761292). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.