A study of Baricitinib compared to placebo in children with Juvenile Idiopathic Arthritis (JIA)

• Register: EUCTR
• Last refreshed on: 7 February 2022
• Main ID: EUCTR2017-004518-24-BE
• Date of registration: 14/08/2019
• Prospective Registration: No
• Primary sponsor: Eli Lilly and Company
• Public title: A study of Baricitinib compared to placebo in children with Juvenile Idiopathic Arthritis (JIA)
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Withdrawal, Safety and Efficacy Study of Oral Baricitinib in Patients from 2 Years to Less Than 18 Years Old with Juvenile Idiopathic Arthritis (JIA)
• Date of first enrolment: 16/07/2019
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004518-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Medication-withdrawal If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, China, Czech Republic, Denmark, France, Germany, India, Israel, Italy, Japan, Mexico, Poland, Russian Federation, Spain, Turkey, United Kingdom

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly and Company

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

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 nonpregnant, nonbreastfeeding female patients. Patients of child-bearing potential who are abstinent or in a same-sex relationship must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with the opposite sex. Otherwise, patients and their partners of childbearing potential must agree to use 2 effective methods of contraception.
Are the trial subjects under 18? yes
Number of subjects for this age range: 225
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Juvenile Idiopathic Arthritis
MedDRA version: 21.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Olumiant
Product Name: Olumiant
Product Code: LY3009104
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BARICITINIB
Other descriptive name: baricitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Olumiant
Product Name: Olumiant
Product Code: LY3009104
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BARICITINIB
Other descriptive name: baricitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Olumiant
Product Code: LY3009104
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BARICITINIB
Other descriptive name: baricitinib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Olumiant
Product Code: LY3009104
Pharmaceutical Form: Suspension for oral suspension
INN or Proposed INN: BARICITINIB
Other descriptive name: baricitinib
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Suspension for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Secondary Objective: 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

Timepoint(s) of evaluation of this end point: At Week 12 and during the DBW period.

Main Objective: The primary objective of this protocol is to evaluate the efficacy of baricitinib compared to placebo in children with JIA

Secondary Outcome(s)

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 health-related QOL as measured by the CHQPF50 during the OLLI period and during the DBW period.
- Changes from baseline in caregiver burden as measured by the parent/family domains of the CHQ-PF50 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 OLLI period and 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 as measured by the CHAQ pain 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

Timepoint(s) of evaluation of this end point: Assessed at each visit, except Visit 3.

Secondary ID(s)

I4V-MC-JAHV

2017-004518-24-GB

Source(s) of Monetary Support

Eli Lilly and Company

Ethics review

Status: Approved
Approval date: 16/07/2019
Contact: