Back to resultsEfficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis
Primary Purpose
Polyarticular Course Juvenile Idiopathic Arthritis
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Givinostat
Sponsored by
About this trial
This is an interventional treatment trial for Polyarticular Course Juvenile Idiopathic Arthritis focused on measuring poly JIA
Eligibility Criteria
Inclusion Criteria:
- patients of both genders, aged 2 to 17 years, with established diagnosis of polyarticular course Juvenile Idiopathic Arthritis (see before for specific subtypes) according to ILAR (International League Against Rheumatism) criteria (Petty RE et al., 2004) for at least six months before the study entry
- age at polyarticular JIA diagnosis < 16 years
- active disease for at least 6 months prior to enrolment as defined by the following criteria:
- presence of at least 5 active joints (those with swelling or, in the absence of swelling, limited range of motion accompanied by pain/tenderness)
- inadequate response to, or intolerance to, at least one biologic agent such as, but not limited to, etanercept, infliximab, and adalimumab.
- maximum allowed steroid dose 0.2 mg/kg/day or 10 mg/day (whichever is lower) of prednisone or equivalent
- in case of concomitant methotrexate treatment, it has to be on a stable dose ≤15 mg/m2 weekly for at least 1 month before patient's enrolment
- other disease-modifying anti-rheumatic drugs possibly previously introduced have to be discontinued for a period of at least five half-lives
- concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at least four weeks before patient's enrolment
Exclusion Criteria:
- patient with fever related to JIA or other systemic features of JIA during 12 months before entering the study
- active bacterial or mycotic infection requiring antimicrobial treatment
- episode of macrophage activation syndrome in the last 6 months
- a baseline prolongation of QT/QTc interval, use of concomitant medications that prolong the QT/QTc interval or history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) (Appendix C)
- clinically significant cardiovascular disease
- clinically significant illness i.e. any condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
- psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
- inherited metabolic diseases
- presence of malignancy
- pregnancy or lactation
- positive blood test for HIV
- active EBV infection, active B and/or C hepatitis
- platelet count <100x109/L
- absolute neutrophil count <1.5x109/L
- serum creatinine >2xULN (Upper limit of normal).
- total serum bilirubin >1.5xULN.
- serum AST/ALT > 3xULN.
- congenital heart and/or central nervous system disorders
Sites / Locations
- Universitair Ziekenhuis Gent
- 1st Faculty of Medicine and General Faculty Hospital
- Ospedale Meyer
- Policlinico G. Martino
- Istituto Gaetano Pini
- Azienda Ospedaliera-Università di Padova
- Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
- Spitalul Clinic de Urgenta pentru Copii "M.S. Curie"
- Mother and Child Health Institute "Dr Vukan Cupic"
- Institute of Rheumatology Belgrade
- University Clinical Center Nis
- Children's Hospital - University Medical Centre Ljubljana
- Hospital Ramón y Cajal
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Givinostat 1.0 mg/kg daily
Givinostat 1.5 mg/kg daily
Arm Description
Outcomes
Primary Outcome Measures
ACR Pediatric Response Level (ACRPRL) 30 After 12 Weeks of Treatment
ACR Pediatric variables include: Physician's Global Assessment of disease activity on a 0-100 mm visual analogue scale from 0 mm = no disease activity to 100 mm = very severe disease activity; Parent's or patient's Global Assessment of Patient's overall well-being on a 100 mm VAS from 0 mm = very well to 100 mm = very poor; Functional ability: Childhood Health Assessment Questionnaire; Number of joints with active arthritis using the ACR definition (any joint with swelling, or in the absence of swelling, limitation of motion accompanied by pain/tenderness not due to bone deformity); Number of joints with limitation of motion; Laboratory measure of inflammation: C-reactive protein (mg/L) Patients were considered as responders if they achieve at least an ACR Pediatric Criteria level 30 of response, defined as a 30% improvement as compared to baseline in at least 3 of the 6 variables listed above, with no more than 1 variable worsening by > than 30%
Secondary Outcome Measures
ACR Pediatric Response Level (ACR 50, 70, 90 and 100) at Week 12
ACR Pediatric variables include: Physician's Global Assessment of disease activity on a 0- 100 mm visual analogue scale from 0 mm = no disease activity to 100 mm = very severe disease activity; Parent's or patient's Global Assessment of Patient's overall well-being on a 100 mm VAS from 0 mm = very well to 100 mm = very poor; Functional ability: Childhood Health Assessment Questionnaire; Number of joints with active arthritis using the ACR definition (any joint with swelling, or in the absence of swelling, limitation of motion accompanied by pain/tenderness not due to bone deformity); Number of joints with limitation of motion; Laboratory measure of inflammation: C-reactive protein (mg/L) Patients were considered as responders if they achieve at least an ACR Pediatric Criteria level 50, 70, 90 and 100 of response, defined as a 50%, 70%, 90% and 100% improvement as compared to baseline in at least 3 of the 6 variables listed above, with no more than 1 variable worsening by > than 30%
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01261624
Brief Title
Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis
Official Title
A Multicenter, Open Label, Dose Finding Study to Evaluate Efficacy and Safety of Givinostat Administered in Two Different Doses in Patients With Poly JIA Not Adequately Responding to the Standard Treatment.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2014
Overall Recruitment Status
Terminated
Why Stopped
The primary reason for the decision to discontinue the study is lack of enrolment; this decision is not related to any tolerability concerns with Givinostat
Study Start Date
October 2010 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Italfarmaco
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The present study has been designed in order to evaluate the efficacy and safety of two doses of Givinostat in subjects with polyarticular course JIA
Givinostat ready-to-use suspension especially intended for paediatric administration, will be administered orally at different daily doses.
Patients with an established diagnosis of one of the following JIA forms (Polyarticular JIA rheumatoid factor positive or negative, Oligoarticular extended JIA, Systemic JIA without active systemic features) will be enrolled.
The treatment regimen will remain unchanged for 12 weeks and the clinical response will by assessed by applying the ACR Pediatric response criteria. Patients achieving at least an ACR Pediatric 30 response will continue receiving the assigned dose for 12 further weeks.
After the end of study (week 24) responder patients will be allowed to extend the treatment until they maintain a clinical benefit.
Detailed Description
Non-clinical data on Givinostat, support a potent anti-inflammatory mechanism of action which can potentially slow the arthritic destructive process. This rationale seems to be confirmed by the preliminary evidences collected in a previous Phase II clinical trial conducted in children and young adults with systemic JIA.
The present protocol is aimed at collecting new information on safety and efficacy of two doses of Givinostat for the treatment of JIA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polyarticular Course Juvenile Idiopathic Arthritis
Keywords
poly JIA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Givinostat 1.0 mg/kg daily
Arm Type
Experimental
Arm Title
Givinostat 1.5 mg/kg daily
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Givinostat
Intervention Description
1.0 mg/kg daily (0.5 mg/kg twice a day) in fed condition 1.5 mg/kg daily (0.75 mg/kg twice a day) in fed condition
Primary Outcome Measure Information:
Title
ACR Pediatric Response Level (ACRPRL) 30 After 12 Weeks of Treatment
Description
ACR Pediatric variables include: Physician's Global Assessment of disease activity on a 0-100 mm visual analogue scale from 0 mm = no disease activity to 100 mm = very severe disease activity; Parent's or patient's Global Assessment of Patient's overall well-being on a 100 mm VAS from 0 mm = very well to 100 mm = very poor; Functional ability: Childhood Health Assessment Questionnaire; Number of joints with active arthritis using the ACR definition (any joint with swelling, or in the absence of swelling, limitation of motion accompanied by pain/tenderness not due to bone deformity); Number of joints with limitation of motion; Laboratory measure of inflammation: C-reactive protein (mg/L) Patients were considered as responders if they achieve at least an ACR Pediatric Criteria level 30 of response, defined as a 30% improvement as compared to baseline in at least 3 of the 6 variables listed above, with no more than 1 variable worsening by > than 30%
Time Frame
12 weeks of treatment
Secondary Outcome Measure Information:
Title
ACR Pediatric Response Level (ACR 50, 70, 90 and 100) at Week 12
Description
ACR Pediatric variables include: Physician's Global Assessment of disease activity on a 0- 100 mm visual analogue scale from 0 mm = no disease activity to 100 mm = very severe disease activity; Parent's or patient's Global Assessment of Patient's overall well-being on a 100 mm VAS from 0 mm = very well to 100 mm = very poor; Functional ability: Childhood Health Assessment Questionnaire; Number of joints with active arthritis using the ACR definition (any joint with swelling, or in the absence of swelling, limitation of motion accompanied by pain/tenderness not due to bone deformity); Number of joints with limitation of motion; Laboratory measure of inflammation: C-reactive protein (mg/L) Patients were considered as responders if they achieve at least an ACR Pediatric Criteria level 50, 70, 90 and 100 of response, defined as a 50%, 70%, 90% and 100% improvement as compared to baseline in at least 3 of the 6 variables listed above, with no more than 1 variable worsening by > than 30%
Time Frame
at week12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients of both genders, aged 2 to 17 years, with established diagnosis of polyarticular course Juvenile Idiopathic Arthritis (see before for specific subtypes) according to ILAR (International League Against Rheumatism) criteria (Petty RE et al., 2004) for at least six months before the study entry
age at polyarticular JIA diagnosis < 16 years
active disease for at least 6 months prior to enrolment as defined by the following criteria:
presence of at least 5 active joints (those with swelling or, in the absence of swelling, limited range of motion accompanied by pain/tenderness)
inadequate response to, or intolerance to, at least one biologic agent such as, but not limited to, etanercept, infliximab, and adalimumab.
maximum allowed steroid dose 0.2 mg/kg/day or 10 mg/day (whichever is lower) of prednisone or equivalent
in case of concomitant methotrexate treatment, it has to be on a stable dose ≤15 mg/m2 weekly for at least 1 month before patient's enrolment
other disease-modifying anti-rheumatic drugs possibly previously introduced have to be discontinued for a period of at least five half-lives
concomitant nonsteroidal anti-inflammatory drugs, if any, on a stable dose for at least four weeks before patient's enrolment
Exclusion Criteria:
patient with fever related to JIA or other systemic features of JIA during 12 months before entering the study
active bacterial or mycotic infection requiring antimicrobial treatment
episode of macrophage activation syndrome in the last 6 months
a baseline prolongation of QT/QTc interval, use of concomitant medications that prolong the QT/QTc interval or history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) (Appendix C)
clinically significant cardiovascular disease
clinically significant illness i.e. any condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
inherited metabolic diseases
presence of malignancy
pregnancy or lactation
positive blood test for HIV
active EBV infection, active B and/or C hepatitis
platelet count <100x109/L
absolute neutrophil count <1.5x109/L
serum creatinine >2xULN (Upper limit of normal).
total serum bilirubin >1.5xULN.
serum AST/ALT > 3xULN.
congenital heart and/or central nervous system disorders
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Zulian, MD
Organizational Affiliation
Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitair Ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
1st Faculty of Medicine and General Faculty Hospital
City
Praha 2
State/Province
Praha
ZIP/Postal Code
12109
Country
Czech Republic
Facility Name
Ospedale Meyer
City
Firenze
State/Province
FI
ZIP/Postal Code
50139
Country
Italy
Facility Name
Policlinico G. Martino
City
Messina
State/Province
ME
ZIP/Postal Code
98125
Country
Italy
Facility Name
Istituto Gaetano Pini
City
Milano
State/Province
MI
ZIP/Postal Code
20122
Country
Italy
Facility Name
Azienda Ospedaliera-Università di Padova
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
City
Bucarest
ZIP/Postal Code
020395
Country
Romania
Facility Name
Spitalul Clinic de Urgenta pentru Copii "M.S. Curie"
City
Bucarest
ZIP/Postal Code
041451
Country
Romania
Facility Name
Mother and Child Health Institute "Dr Vukan Cupic"
City
Novi Beograd
State/Province
Belgrade
ZIP/Postal Code
11070
Country
Serbia
Facility Name
Institute of Rheumatology Belgrade
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
University Clinical Center Nis
City
Nis
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Children's Hospital - University Medical Centre Ljubljana
City
Ljubljana
ZIP/Postal Code
SI-1000
Country
Slovenia
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
12. IPD Sharing Statement
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Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis
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