Open Label, Multicentre Trial to Assess Safety and Efficacy of ITF2357 in Active Systemic Juvenile Idiopathic Arthritis

NCT00570661 | Completed Phase 2 Results

• 1 other identifier: DSC/05/2357/19
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 5

Brief Summary

This study has the following objectives: Primary objective: \- To determine the safety and tolerability of oral ITF2357 in patients with active SOJIA with inadequate response or intolerance to standard therapy with oral steroids and methotrexate, with or without previously used biologic agents. Secondary objectives:

• to evaluate the effect of ITF2357 on disease activity in patients with active SOJIA
• to investigate the possibility of steroid dose tapering in patients with active SOJIA during ITF2357 treatment
• to assess the effect of ITF2357 on levels of circulating cytokines
• to assess the pharmacokinetic properties of ITF2357

Conditions

Active Systemic; Onset Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Patients Completing Week 12 of Treatment

  The primary endpoint describes the number of patients who has completed week 12 of treatment with ITF2357, both in the Per protocol (PP) population and in the Intention to treat (ITT) population. ITF2357 hard gelatine capsules were administered orally, in fed conditions, at the cumulative daily dose of 1.5 mg/kg achieved by administration of 0.75 mg/kg at 12-hour interval for 4 weeks initially. The doses of 1.5 mg/kg/day were achieved by administration of an appropriate number of capsules of definite strength. Treatment was further prolonged up to 12 weeks in total if so suggested by the observed benefits and the lack of treatment-limiting toxicity.

  At week 12

Secondary Outcomes (19)

• JIA Outcome Core Set Variables - Patient Global Assessment

  At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

• JIA Outcome Core Set Variables - Physician Global Assessment

  At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

• JIA Outcome Core Set Variables - Number of Joints With Active Arthritis

  At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

• JIA Outcome Core Set Variables - Number of Joints With Limitation

  At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

• JIA Outcome Core Set Variables - CHAQ

  At pretreatment visit, at weeks 2, 4, 6, 8, 10 and 12 (End of treatment), 1 month and 3 months follow up (FU1, FU3) in the PP and ITT populations respectively.

Study Arms (1)

ITF2357

EXPERIMENTAL

ITF2357 hard gelatine capsules were administered orally, in fed conditions, at the cumulative daily dose of 1.5 mg/kg achieved by administration of 0.75 mg/kg at 12-hour interval for 4 weeks initially. The doses of 1.5 mg/kg/day were achieved by administration of an appropriate number of capsules of definite strength (dose strengths of 7.5, 10, 12.5, 15, 20 mg and 50 mg). Treatment was further prolonged up to 12 weeks in total if so suggested by the observed benefits and the lack of treatment-limiting toxicity

Drug: ITF2357

Interventions

ITF2357 DRUG

ITF2357 orally administered at the cumulative daily dose of 1.5 mg/kg, achieved by administration of different dose strengths identifiable by different colours.

Also known as: Givinostat, histone deacetylase inhibitor

ITF2357

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Established diagnosis of Systemic SOJIA according to ILAR criteria for at least six months before the study entry, with inadequate response or intolerance to standard therapy with oral steroids and/or methotrexate, with or without previously used biologic agents.
• Active disease for at least one month prior to enrolment as defined by the following criteria:
• Presence of arthritis plus at least one of the following:
• Fever, defined as a body temperature \>= 37,5 C degree at least once a day during at least five consecutive days or presence of typical SOJIA intermittent temperature chart
• Rash, defined by presence of typical SOJIA salmon pink rash on the trunk and elsewhere during the febrile episodes
• Serositis (pericarditis, pleuritis, peritonitis) confirmed by ultrasound and/or X-ray exploration or by presence of typical ECG findings in the case of pericarditis
• Lymphadenopathy, defined by lymph nodes enlargement to 1,5 cm or more localized anywhere within the body, and/or hepatomegaly and/or splenomegaly, confirmed by ultrasound evaluation and established after comparison to age standards for organ size
• ESR \>= 20 mm/h (first hour) and/or CRP \>= 10 mg/L. in the absence of arthritis, two definite or one definite and one probable diagnostic criteria plus ESR \>=20 mm/h (first hour) and/or CRP \>=10 mg/L
• Age at enrolment between 2 and 25 years
• Age at first SOJIA diagnosis \< 16 years
• Previously introduced standard treatment of disease with steroids without satisfactory effect and concomitant treatment with oral steroids at a dose equivalent to \>= 0,2 mg/kg/day of prednisolone, unmodified for at least four weeks before patient's enrolment
• In case of concomitant methotrexate treatment, it has to be on stable dose \>= 10mg/m2 weekly for al least 4 weeks before pt enrollment
• Previous treatment with biologics, if any, during at least three months without satisfactory effect or with drug intolerability, discontinued for at least the period specified below before patient's enrolment:
• Two months for etanercept
• Six months for infliximab

You may not qualify if:

• Ongoing clinical relevant viral infection (eg.: Herpes Zoster, Ebstein barr, CMV, Systemic fungal infections or history of recurrent serious bacterial infection)
• History of macrophage activation syndrome
• 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
• Congenital heart and/or central nervous system disorders
• Inherited metabolic diseases
• Positive serological testing for anti HCV, anti HIV and HBsAg (to be performed at screening)
• Pregnant or lactating women
• Presence of malignancy
• Any previous evidence, irrespective of its severity, of coronary disease, cardiac rhythm abnormalities or congestive heart failure
• QTc interval \> 450 msec at screening evaluation
• Serum magnesium and potassium below the LLN at screening
• Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (5)

Clinica Institute Fundeni.Pediatric Clinic 258 Sos. Fundeni,

Bucharest, 022328, Romania

Location

Clinical Emergency Children Hospital "M.S. Curie" Paediatric Clinic no. I 20 Ctin. Brancoveanu Bvd., 041451 Bucharest 4th district

Bucharest, 041451, Romania

Location

University Clinical Centre NisClinic of Paediatrics Department for Rheumatology Bul Dr Zoran Djindjica

Niš, Nis, 18000, Serbia

Location

Mother and Child Health Institute "Dr. Vukan Cupic" Clinic of Paediatrics Radoja Dakica

Belgrade, Novi Belgrade, 6-811070, Serbia

Location

Institute of Rheumatology Belgrade Resavska

Belgrade, 6911000, Serbia

Location

Related Publications (2)

• Vojinovic J, Damjanov N, D'Urzo C, Furlan A, Susic G, Pasic S, Iagaru N, Stefan M, Dinarello CA. Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2011 May;63(5):1452-8. doi: 10.1002/art.30238.

  PMID: 21538322 DERIVED

• Vojinovic J, Damjanov N. HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol Med. 2011 May-Jun;17(5-6):397-403. doi: 10.2119/molmed.2011.00030. Epub 2011 Feb 4.

  PMID: 21308151 DERIVED

MeSH Terms

Interventions

givinostat hydrochloride; givinostat; Histone Deacetylase Inhibitors

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Maurizio Caserini, MD
• Organization: Italfarmaco SpA

m.caserini@italfarmaco.com

+39 0264431

Study Officials

• Nemanja Damjanov, MD, PhD

  Institute of Rheumatology Belgrade

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Not applicable. The study was open label.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2007
• First Posted: December 11, 2007
• Study Start: September 12, 2006
• Primary Completion: August 25, 2008
• Study Completion: June 10, 2013
• Last Updated: May 4, 2021
• Results First Posted: May 4, 2021

Record last verified: 2021-04

Locations

SE (3); RO (2)