| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Juvenile Idiopathic Arthritis |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10059176 |
| E.1.2 | Term | Juvenile idiopathic arthritis |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this protocol is to evaluate the efficacy of baricitinib compared to placebo in children with JIA |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate:
- to evaluate the efficacy of baricitinib in children with JIA
- to evaluate the efficacy of baricitinib compared to placebo in children with JIA
- to assess the efficacy of baricitinib in children with JPsA
- to assess the efficacy of baricitinib compared to placebo in children with JPsA
- to assess the efficacy of baricitinib in children with ERA or JPsA
- to assess the efficacy of baricitinib compared to placebo in children with ERA or JPsA
- to evaluate the potential effects of baricitinib on the cellular and humoral immune system
- to characterize baricitinib PK in the JIA population and explore relationships between baricitinib exposure and study endpoints
- to assess the patient acceptability and palatability of baricitinib tablets and oral suspension
- to assess the safety of baricitinib compared to placebo in patients with JIA |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
[1] Patients are at least 2 years and less than 18 years of age.
[2] Have a diagnosis with onset before the age of 16 years of any of the following
forms of JIA as defined by ILAR criteria:
Polyarticular JIA (positive or negative for RF)
Extended oligoarticular JIA
ERA
JPsA
[3] Have had an inadequate response or intolerance to treatment with ≥1 conventional or bDMARD.
[4] Patients with polyarticular JIA or extended oligoarticular JIA must have at least 5 active joints at screening and baseline. Those with JPsA must have at least 3 active joints at screening and baseline. Those with ERA must have (a) at least 3 active joints at screening and baseline or (b) involvement of at least 1 sacroiliac joint AND a physician global of at least 3 (on the 21-circle numeric rating scale [NRS]).
[5] Both the child or adolescent and a parent or legal guardian are able to understand and fully participate in the activities of the clinical study and sign their assent and consent, respectively, accordance to local guidelines.
[6] Male or non-pregnant, non-breastfeeding female patients. Patients of child-bearing potential who are abstinent (if this is complete abstinence,
and their preferred and usual lifestyle). Otherwise, patients and their partners of childbearing potential must agree to use 2 effective methods
of contraception. |
|
| E.4 | Principal exclusion criteria |
[7] Have systemic JIA, as defined by ILAR criteria, with or without active systemic
features.
[8] Have persistent oligoarticular arthritis as defined by ILAR criteria.
[9] Have a history or presence of any autoimmune inflammatory condition other than JIA, such as Crohn’s disease or ulcerative colitis.
[11] Have active fibromyalgia or other chronic pain conditions that, in the investigator’s opinion, would make it difficult to appropriately assess disease activity for the purposes of this study.
[12] Have a current or recent (<4 weeks prior to baseline) clinically serious viral,
bacterial, fungal, or parasitic infection or any other active or recent infection that, in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
[13] Bone, joint infections within 6 months prior to screening.
[17] Have a positive test for hepatitis B virus (HBV) at screening.
[18] Have hepatitis C virus (HCV) infection.
[19] Have evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies.
[21] Have evidence of active TB or latent TB.
[22] Major surgery within 8 weeks prior to screening or requiring major surgery during the study.
[23] History or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness.
[24] History of a VTE or are considered at high risk of VTE as deemed by the investigator.
[25] Largely or wholly incapacitated, such as being bedridden.
[26] History of lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have primary or recurrent malignant disease.
[27] History of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse within the 2 years prior to screening.
[28] Presence of significant uncontrolled neuropsychiatric disorder, history of a suicide attempt or suicidal ideation, or clinically judged by the investigator to be at risk for suicide.
[31] Have initiated or changed dosage of concomitant cDMARDs (other than MTX) within 4 weeks prior to screening (such as, but not limited to, hydroxychloroquine, sulfasalazine, gold salts, cyclosporine, or azathioprine). The dose of cDMARDs is expected to remain stable throughout the study and may be adjusted only for safety reasons.
[32] MTX use at doses of >20 mg/m2/week.
[33] Are currently receiving concomitant treatment with combination of >2 cDMARDs (including MTX).
[51] Have experienced hypersensitivity to the active substance or to any of the excipients. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Time to disease flare from Week 12 to the end of the DBW period.
Disease flare is defined as a worsening of ≥30% in at least 3 of the 6 PedACR core criteria for JIA and an improvement of ≥30% in no more than 1 of the criteria from the patient's condition at the conclusion of the OLLI period. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At Week 12 and during the DBW period. |
|
| E.5.2 | Secondary end point(s) |
- Proportion of patients with disease flare during the DBW period.
- Changes from baseline in each of the 6 individual components of the PedACR core set variables during the OLLI period and during the DBW period.
- PedACR30/50/70/90/100 response rates during the during the OLLI period and during the DBW period.
- Changes from baseline in the Physical Summary Score (PhS) and Psychosocial Summary Score (PsS) of the Child Health Questionnaire-Parent Form 50 (CHQ-PF50) during the OLLI period and during the DBW period.
- Changes from baseline in caregiver burden as measured by the Parental Impact-Time and Parental Impact-Emotion scales of the CHQPF50 during the OLLI period and during the DBW period.
- Proportion of patients with inactive disease (as defined by Wallace et al. 2011) during the OLLI period and during the DBW period.
- Proportion of patients in remission (as defined by Wallace et al. 2011) during the DBW period.
- Proportion of patients with minimal disease activity (as defined by Consolaro et al. 2012) during the OLLI period and during the DBW period.
- Change from baseline in JADAS-27 during the OLLI period and during the DBW period.
- Changes from baseline in arthritis-related pain severity as measured by the CHAQ pain severity VAS item during the OLLI period and during the
DBW period.
- In patients with JPsA:
o Change from baseline in PASI score during the OLLI period and during the DBW period.
- In patients with JPsA or ERA:
o Change from baseline in SPARCC enthesitis index during the OLLI period and during the DBW period.
o Change from baseline in the JSpADA during the OLLI period and during the DBW period.
- Change in immunoglobulin levels and peripheral blood immunophenotyping (including T and B cells, T cell subsets, and NK cells) from baseline during the OLLI period and during the DBW period.
- Change of IgG titers from pre-vaccination to 4 weeks and 12 week post-vaccination in patients eligible for vaccination with TDaP and/or pneumococcal conjugate vaccine according to local guidelines.
- Assessment of tablet or oral suspension product acceptability and palatability at baseline and Week 12.
-S afety variables |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Assessed at each visit, except Visit 3. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 41 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Brazil |
| China |
| India |
| Israel |
| Japan |
| Mexico |
| Russian Federation |
| Turkey |
| Austria |
| Belgium |
| Czechia |
| Denmark |
| France |
| Germany |
| Italy |
| Poland |
| Spain |
| United Kingdom |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The date of the last visit or last scheduled procedure for the last patient
in the 28-day follow-up period. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 6 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 3 |
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