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

NCT01261624 | Terminated Phase 2 Results

• 1 other identifier: DSC/08/2357/36
• Study Type: interventional
• Target: 16
• Locations: 7 countries
• Sites: 13

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.

Conditions

Polyarticular Course Juvenile Idiopathic Arthritis

Keywords

poly JIA

Outcome Measures

Primary Outcomes (1)

• 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%

  12 weeks of treatment

Secondary Outcomes (1)

• ACR Pediatric Response Level (ACR 50, 70, 90 and 100) at Week 12

  at week12

Study Arms (2)

Givinostat 1.0 mg/kg daily

EXPERIMENTAL

Drug: Givinostat

Givinostat 1.5 mg/kg daily

EXPERIMENTAL

Drug: Givinostat

Interventions

Givinostat DRUG

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

Givinostat 1.0 mg/kg daily; Givinostat 1.5 mg/kg daily

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (13)

Universitair Ziekenhuis Gent

Ghent, Gent, 9000, Belgium

Location

1st Faculty of Medicine and General Faculty Hospital

Prague, Prague, 12109, Czechia

Location

Ospedale Meyer

Florence, FI, 50139, Italy

Location

Policlinico G. Martino

Messina, ME, 98125, Italy

Location

Istituto Gaetano Pini

Milan, MI, 20122, Italy

Location

Azienda Ospedaliera-Università di Padova

Padua, PD, 35128, Italy

Location

Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"

Bucharest, București, 020395, Romania

Location

Spitalul Clinic de Urgenta pentru Copii "M.S. Curie"

Bucharest, București, 041451, Romania

Location

Institute of Rheumatology Belgrade

Belgrade, Belgrade, 11000, Serbia

Location

Mother and Child Health Institute "Dr Vukan Cupic"

New Belgrade, Belgrade, 11070, Serbia

Location

University Clinical Center Nis

Niš, Nis, 18000, Serbia

Location

Children's Hospital - University Medical Centre Ljubljana

Ljubljana, Ljubljana, SI-1000, Slovenia

Location

Hospital Ramón y Cajal

Madrid, Madrid, 28034, Spain

Location

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

givinostat

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Clinical R&D Director
• Organization: Italfarmaco S.p.A.

p.bettica@italfarmaco.com

026443

Study Officials

• Francesco Zulian, MD

  Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 16, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 16, 2014
• Results First Posted: April 16, 2014

Record last verified: 2014-03

Locations

ES (1); CZ (1); BE (1); SE (3); IT (4); RO (2); SL (1)