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Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis

This study has been terminated.
(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)
Sponsor:
Information provided by (Responsible Party):
Italfarmaco
ClinicalTrials.gov Identifier:
NCT01261624
First received: December 15, 2010
Last updated: March 11, 2014
Last verified: March 2014

December 15, 2010
March 11, 2014
October 2010
June 2012   (final data collection date for primary outcome measure)
ACR Pediatric Response Level (ACRPRL) 30 After 12 Weeks of Treatment [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]
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%
ACR pediatric 30 level of response after 12 weeks of treatment [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01261624 on ClinicalTrials.gov Archive Site
ACR Pediatric Response Level (ACR 50, 70, 90 and 100) at Week 12 [ Time Frame: at week12 ] [ Designated as safety issue: No ]
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%
  • ACR paediatric level of response (ACR 50, 70, 90 and 100) at week 12 [ Time Frame: at week12 ] [ Designated as safety issue: No ]
  • Mean changes over time of the 6 ACR Pediatric variables [ Time Frame: at week 12 ] [ Designated as safety issue: No ]
  • Safety (number of patients experiencing adverse events; type, incidence, and severity of treatment-related adverse events) [ Time Frame: every visit ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis
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.

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Polyarticular Course Juvenile Idiopathic Arthritis
Drug: Givinostat
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
  • Experimental: Givinostat 1.0 mg/kg daily
    Intervention: Drug: Givinostat
  • Experimental: Givinostat 1.5 mg/kg daily
    Intervention: Drug: Givinostat
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
16
March 2013
June 2012   (final data collection date for primary outcome measure)

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
Both
2 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Czech Republic,   Italy,   Romania,   Serbia,   Slovenia,   Spain
 
NCT01261624
DSC/08/2357/36
No
Italfarmaco
Italfarmaco
Not Provided
Principal Investigator: Francesco Zulian, MD Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica
Italfarmaco
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP