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
  Purpose

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.


Condition Intervention Phase
Polyarticular Course Juvenile Idiopathic Arthritis
Drug: Givinostat
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Italfarmaco:

Primary Outcome Measures:
  • 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%


Secondary Outcome Measures:
  • 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%


Enrollment: 16
Study Start Date: October 2010
Study Completion Date: March 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Givinostat 1.0 mg/kg daily 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 1.5 mg/kg daily 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

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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01261624

Locations
Belgium
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Czech Republic
1st Faculty of Medicine and General Faculty Hospital
Praha 2, Praha, Czech Republic, 12109
Italy
Ospedale Meyer
Firenze, FI, Italy, 50139
Policlinico G. Martino
Messina, ME, Italy, 98125
Istituto Gaetano Pini
Milano, MI, Italy, 20122
Azienda Ospedaliera-Università di Padova
Padova, PD, Italy, 35128
Romania
Spitalul Clinic de Urgenta pentru Copii "M.S. Curie"
Bucarest, Romania, 041451
Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
Bucarest, Romania, 020395
Serbia
Mother and Child Health Institute "Dr Vukan Cupic"
Novi Beograd, Belgrade, Serbia, 11070
Institute of Rheumatology Belgrade
Belgrade, Serbia, 11000
University Clinical Center Nis
Nis, Serbia, 18000
Slovenia
Children's Hospital - University Medical Centre Ljubljana
Ljubljana, Slovenia, SI-1000
Spain
Hospital Ramón y Cajal
Madrid, Spain, 28034
Sponsors and Collaborators
Italfarmaco
Investigators
Principal Investigator: Francesco Zulian, MD Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica
  More Information

No publications provided

Responsible Party: Italfarmaco
ClinicalTrials.gov Identifier: NCT01261624     History of Changes
Other Study ID Numbers: DSC/08/2357/36
Study First Received: December 15, 2010
Results First Received: January 14, 2014
Last Updated: March 11, 2014
Health Authority: Czech Republic: State Institute for Drug Control
Slovenia: Javna agencija Republike Slovenije za zdravila in medicinske pripomočke
Sweden: Medical Products Agency
Spain: Ministerio de Sanidad y Consumo-Agencia Española de Medicamentos y Productos Sanitarios Republic of Serbia: Medicines and Medical Devices Agency of Serbia
Romania: National Medicine and Medical Devices Agency
Belgium: Agence Fédérale des Médicaments et des Produits de Santé (AFMPS)

Keywords provided by Italfarmaco:
poly JIA

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 25, 2014