Polyarticular Course Juvenile Idiopathic ArthritisPhase 2NCT01261624
Efficacy and Safety Dose Finding Study of Givinostat to Treat Polyarticular Course Juvenile Idiopathic Arthritis
A Phase 2 study testing Givinostat in people with Polyarticular Course Juvenile Idiopathic Arthritis, run by Italfarmaco at 13 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Polyarticular Course Juvenile Idiopathic Arthritis
- What is being tested?
- Givinostat
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 13 sitesin 7 countries
- Study dates
- Oct 2010to Mar 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
Italy4 sites
Ospedale Meyer
Florence, FI, 50139
Policlinico G. Martino
Messina, ME, 98125
Istituto Gaetano Pini
Milan, MI, 20122
Azienda Ospedaliera-Università di Padova
Padova, PD, 35128
Serbia3 sites
Institute of Rheumatology Belgrade
Belgrade, Belgrade, 11000
Mother and Child Health Institute "Dr Vukan Cupic"
New Belgrade, Belgrade, 11070
University Clinical Center Nis
Niš, Nis, 18000
Romania2 sites
Institutul pentru Ocrotirea Mamei si Copilului "Alfred Rusescu"
Bucharest, Bucharest, 020395
Spitalul Clinic de Urgenta pentru Copii "M.S. Curie"
Bucharest, Bucharest, 041451
Czechia1 site
1st Faculty of Medicine and General Faculty Hospital
Prague, Prague, 12109
Slovenia1 site
Children's Hospital - University Medical Centre Ljubljana
Ljubljana, Ljubljana, SI-1000
About this study
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.
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.
Read more
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.
Read the 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.
- Being tested
- Givinostat
- Keywords
- poly JIA
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GivinostatDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Givinostat 1.0 mg/kg daily | Experimental | Not described Receives: Drug: Givinostat |
| Givinostat 1.5 mg/kg daily | Experimental | Not described Receives: Drug: Givinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: 12 weeks of treatment
Secondary outcomes (1)
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%
Measured: at week12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2012
- Study completionMar 2013
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Polyarticular Course Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italfarmaco
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Francesco Zulian, MD, Principal investigator, Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01261624
- Sponsor's protocol ID
- DSC/08/2357/36
- Status last verified
- Mar 2014
- First submitted
- 15 Dec 2010
- Last updated
- 16 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01261624
- Acronym / sponsor ID
- DSC/08/2357/36
- Keywords
- poly JIA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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
- Enrolment
- 16 participants (actual)
- Lead sponsor
- ItalfarmacoIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 16 Dec 2010 (estimated)
- Results
- Posted 16 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Givinostat 1.0 mg/kg daily | Experimental | Drug: Givinostat |
| Givinostat 1.5 mg/kg daily | Experimental | Drug: Givinostat |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Givinostat1.0 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 | Drug | Givinostat 1.0 mg/kg daily, Givinostat 1.5 mg/kg daily |
Primary outcome
ACR Pediatric Response Level (ACRPRL) 30 After 12 Weeks of Treatment
Time frame: 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%
1 secondary outcome
ACR Pediatric Response Level (ACR 50, 70, 90 and 100) at Week 12
Time frame: at week12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Zulian, MD principal investigator
Azienda Ospedaliera-Università di Padova - Unità di Reumatologia Pediatrica
13 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Givinostat in people with Polyarticular Course Juvenile Idiopathic Arthritis, run by Italfarmaco at 13 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Italy, Serbia, Romania, Belgium, Czechia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ACR Pediatric Response Level (ACRPRL) 30 After 12 Weeks of Treatment (time frame: 12 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2014.