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A Study of Baricitinib in Participants From 2 Years to Less Than 18 Years Old With Juvenile Idiopathic Arthritis (JUVE-BASIS)

Primary Purpose

Juvenile Idiopathic Arthritis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Baricitinib

Placebo

About this trial

This is an interventional treatment trial for Juvenile Idiopathic Arthritis focused on measuring Polyarticular JIA, Oligoarthritis, Juvenile psoriatic arthritis (JPsA), Enthesitis-related juvenile idiopathic arthritis (ERA)

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants must have had a diagnosis of active JIA (polyarticular, extended oligoarticular, or enthesitis-related juvenile idiopathic arthritis [ERA] including JPsA).
Participants must have had an inadequate response to at least one conventional or biologic disease-modifying antirheumatic drug (DMARD).

Exclusion Criteria:

Participants must not have systemic JIA, with or without active systemic features.
Participants must not have persistent oligoarticular arthritis.
Participants must not have been previously treated with a Janus kinase (JAK) inhibitor.

Sites / Locations

Instituto CAICI SRL
Centro Medico Privado de Reumatologia
Hospital General de Niños Dr. Pedro de Elizalde
The Sydney Children's Hospitals Network
Royal Childrens Hospital Melbourne
Perth Children's Hospital
LKH Bregenz
AKH
UCL- Saint Luc
UZ Gent-Reuma
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
CMIP - Centro Mineiro de Pesquisa
Faculdade de Medicina de Botucatu
Faculdade de Ciências Médicas - UNICAMP
Universidade Federal de São Paulo - Escola Paulista de Medicina
Children's hospital of Nanjing
Children's Hospital of Chongqing Medical University
Capitol Institute of Pediatrics Children'S Hospital
Beijing Children's hospital, Capital Medical University
Children's Hospital of Soochow University
Centrum detske revmatologie VFN, Klinika detskeho a dorostoveho lekarstvi 1.LFUK a VFN v Praze
Fakultni Nemocnice v Motole
Paediatric rheumatology Unit
Center for Børnereumatologi. Børn og Unge, Århus Universitetshospital
Hospices Civils de Lyon - Hôpital Femme Mère Enfant
Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre
Centre Hospitalier Universitaire de Nîmes - Hôpital Universitaire Carémeau
GH Necker - Enfants Malades
CHU la Miletrie
Universitätsklinikum Heidelberg
Universitätsklinikum Tübingen
Asklepios Klinik Sankt Augustin
HELIOS Klinikum Berlin-Buch
Charité Universitätsmedizin Berlin Campus Buch
Schön Klinik Hamburg Eilbek
Sri Ramachandra MedicaL College & Research Institute
Sir Ganga Ram Hospital
Christian Medical College Vellore
Rambam Medical Center
Meir Medical Center
Schneider Children's Medical Center
Sheba Medical Center
ASST Spedali Civili - Università degli Studi
Ospedale SS. Annunziata
Azienda Ospedaliero Universitaria Meyer
Ospedale Pediatrico Gaslini - Istituto Giannina Gaslini
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
Azienda Ospedaliera Universitaria Federico II
Ospedale Infantile Burlo Garofolo
Kanazawa University Hospital
Kanagawa Children's Medical Center
Yokohama City University Hospital
Miyagi Children's Hospital
Osaka Medical ＆ Pharma Univ Hp
Saitama Children's Medical Center
Tokyo Medical And Dental University Medical Hospital
St. Lukes International Hospital
Tokyo Women's Medical University Hospital
Kagoshima University Hospital
Niigata University Medical & Dental Hospital
Clinstile, S.A. de C.V.
CREA de Guadalajara, S.C.
Hospital Univ. "Dr. José Eleuterio González"
Investigacion y Biomedicina de Chihuahua
Instituto de Investigaciones Aplicadas a la Neurociencia A.C
Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie
CSK, Uniwersyteckie Centrum Pediatrii im.M.Konopnickiej,Klinika Kardiologii i Reumatologii Dzieciecej
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji
V.A. Nasonova Research Institute of Rheumatology
Morozovsky Children's City Clinical Hospital
First Moscow State Medical University n.a. Sechenov
Scientific Center of Children's Health
Saint-Petersburg State Pediatric Medical University
Hospital Sant Joan de Deu
Complexo Hospitalario Universitario A Coruña, CHUAC
Hospital Infantil Universitario Niño Jesús
Hospital Universitario Ramón y Cajal
Hospital Universitario La Paz
Hospital Universitario La Fe de Valencia
Istanbul University Cerrahpasa Medical Faculty
Dokuz Eylul University Hospital
University College Hospital - London
Great Ormond Street Hospital For Children NHS Foundation Trust
Sheffield Children's Hospital
Bristol Royal Hospital for Children
Alder Hey Children's NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Baricitinib

Placebo

Arm Description

Baricitinib was administered QD (once daily) as a 4-mg oral tablet for adolescent participants (12 to <18 years of age) and children ≥9 years of age; and 2 mg for children <9 years of age. Participants <6 years of age received an oral suspension. Participants ≥6 to <12 years old had the option of receiving an oral suspension. Participants >12 years old were supplied tablets. The oral suspension dose was administered as 4-mg, 2-mg, 1-mg, and 0.5-mg as needed.

Placebo matched to baricitinib was administered to participants during the DBW period.

Outcomes

Primary Outcome Measures

Time to Disease Flare

A disease flare is defined as a worsening of 30% or more in at least three of the six core Paediatric American College of Rheumatology (PedACR) criteria for juvenile rheumatoid arthritis (JIA) and an improvement of 30% or more in no more than one of the criteria. The six PedACR criteria are: 1) the number of active joints, 2) the number of joints with limited range of motion, 3) physician's global assessment of disease activity, 4) parent's global assessment of the participant's overall well-being, 5) physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ) and 6) acute-phase reactant (high-sensitivity C-reactive protein [hsCRP] and erythrocyte sedimentation rate [ESR]), the ESR measure is only used as an acute phase reactant in the core criteria.

Secondary Outcome Measures

Percentage of Participants Achieving PedACR30 Responder Index

The PedACR30 response is defined as at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The 6 core response variables included in the PedACR criteria are: Number of active joints (defined as a joint that is swollen or in the absence of swelling has loss of passive motion accompanied by either pain on motion or joint tenderness) in 73 joints, Number of joints with limited range of motion in 69 joints, Physician's Global Assessment of Disease Activity (21-circle visual analogue scale [VAS]), Parent's Global Assessment of Patient's Overall Well-being, Physical function as assessed by the CHAQ and Acute-phase reactant (hsCRP and ESR). When PedACR response is analyzed as secondary endpoint, ESR measure is only used as acute-phase reactant in the core criteria.

Percentage of Participants Achieving PedACR50 Responder Index

The PedACR50 response is defined as at least 50% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by > 30%. The 6 core response variables included in the PedACR criteria are: Number of active joints (defined as a joint that is swollen or in the absence of swelling has loss of passive motion accompanied by either pain on motion or joint tenderness) in 73 joints, Number of joints with limited range of motion in 69 joints, Physician's Global Assessment of Disease Activity (21-circle VAS), Parent's Global Assessment of Patient's Overall Well-being, Physical function as assessed by the CHAQ and Acute-phase reactant (hsCRP and ESR). When PedACR response is analyzed as secondary endpoint, ESR measure is only used as acute-phase reactant in the core criteria.

Percentage of Participants Achieving PedACR70 Responder Index

The PedACR70 response is defined as at least 70% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by > 30%. The 6 core response variables included in the PedACR criteria are: Number of active joints (defined as a joint that is swollen or in the absence of swelling has loss of passive motion accompanied by either pain on motion or joint tenderness) in 73 joints, Number of joints with limited range of motion in 69 joints, Physician's Global Assessment of Disease Activity (21-circle VAS), Parent's Global Assessment of Patient's Overall Well-being, Physical function as assessed by the CHAQ and Acute-phase reactant (hsCRP and ESR). When PedACR response is analyzed as secondary endpoint, ESR measure is only used as acute-phase reactant in the core criteria.

Percentage of Participants Achieving PedACR90 Responder Index

The PedACR90 response is defined as at least 90% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by > 30%. The 6 core response variables included in the PedACR criteria are: Number of active joints (defined as a joint that is swollen or in the absence of swelling has loss of passive motion accompanied by either pain on motion or joint tenderness) in 73 joints, Number of joints with limited range of motion in 69 joints, Physician's Global Assessment of Disease Activity (21-circle VAS), Parent's Global Assessment of Patient's Overall Well-being, Physical function as assessed by the CHAQ and Acute-phase reactant (hsCRP and ESR). When PedACR response is analyzed as secondary endpoint, ESR measure is only used as acute-phase reactant in the core criteria.

Percentage of Participants Achieving PedACR100 Responder Index

The PedACR100 response is defined as at least 100% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by > 30%. The 6 core response variables included in the PedACR criteria are: Number of active joints (defined as a joint that is swollen or in the absence of swelling has loss of passive motion accompanied by either pain on motion or joint tenderness) in 73 joints, Number of joints with limited range of motion in 69 joints, Physician's Global Assessment of Disease Activity (21-circle VAS), Parent's Global Assessment of Patient's Overall Well-being, Physical function as assessed by the CHAQ and Acute-phase reactant (hsCRP and ESR). When PedACR response is analyzed as secondary endpoint, ESR measure is only used as acute-phase reactant in the core criteria.

Percentage of Participants With Inactive Disease

Inactive disease is defined as the presence of all of the following: No joints with active arthritis based on Juvenile Arthritis Disease Activity Score (JADAS) - 27 score, No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to JIA as assessed by the investigator, No active uveitis as assessed by the investigator, Normal ESR or hsCRP (i.e., within normal limits in the local laboratory or, if elevated, not attributable to JIA), Physician's Global Assessment of Disease Activity indicating no active disease (Score ranges are 0 to 100 and best possible score on scale is 0) and Duration of morning stiffness ≤15 minutes.

Percentage of Participants With Minimal Disease Activity

Minimal disease activity is calculated based on the scores from the Physician's Global Assessment of Disease Activity Parent's Global Assessment of Well-Being and the number of swollen joints. If the physician's global assessment of disease activity is ≤3.5 (score range: 0-100), the parent's global rating of patient's overall well-being is ≤2.5 (score range: 0-100), and the swollen joint count is ≤1 (score range: 0-73), then the participant reaches minimal disease activity. if not, minimal disease activity is not reached.

Percentage of Participants in Remission

Remission is defined as inactive disease for at least 24 consecutive weeks. Inactive disease is defined as the presence of all of the following: 1) No joints with active arthritis based on Juvenile Arthritis Disease Activity Score (JADAS)-27 score, 2) No fever, rash, serositis, splenomegaly, hepatomegaly, or generalized lymphadenopathy attributable to JIA as assessed by the investigator, 3) No active uveitis as assessed by the investigator, 4) Normal ESR or hsCRP (i.e., within normal limits in the local laboratory or, if elevated, not attributable to JIA), 5) Physician's Global Assessment of Disease Activity indicating no active disease (best possible score on scale [0]) and 6) Duration of morning stiffness ≤15 minutes.

Change From Baseline in Juvenile Arthritis Disease Activity Score-27 (JADAS-27) Score

The JADAS-27 score is based on 4 components: 1) Physician's global assessment of disease activity on a 0-100 mm VAS, 2) Parent's global assessment of overall well-being on a 0-100 mm VAS, 3) normalized ESR and 4) number of joints (maximum of 27) with active arthritis (cervical spine, elbows, wrists, metacarpophalangeal joints [from first to third], proximal interphalangeal joints, hips, knees, and ankles). The scores for the each of the first 3 components range from 0 -10; the score for the final component ranges from 0-27. The overall JADAS-27 score is sum of the 4 components and it ranges from 0-57. A higher score indicates more disease activity. Least square (LS) mean was calculated using Analysis of covariance (ANCOVA) model which includes treatment, baseline, prior biologic JIA therapy, combined JIA category and predose exposure ESR category value as fixed factors.

Change From Baseline in Arthritis-Related Pain Severity as Measured by the Childhood Health Assessment Questionnaire (CHAQ) Pain Visual Analog Scale (VAS) Item

CHAQ assesses the health status and physical function of children with juvenile arthritis over the past week. The CHAQ consists of a Disability Index and a Discomfort Index. The disability index consisted of 30 items grouped into the following 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities. Each item is scored from 0 to 3 (0 = no difficulty; 1 = some difficulty; 2 = much difficulty and 3 = unable to do or not applicable). The scores of 8 domains were averaged to calculate the CHAQ-Disability Index total score. A higher score indicates worse physical function. The discomfort index consisted of Parent's Global Assessment of Well-Being and pain assessment due to illness. The intensity of pain is scored on a VAS scale ranging from 0-100 mm, with zero referring to "no pain" and 100 referring to "very severe pain". A higher score indicates a worse outcome.

Change From Baseline in Psoriasis Area and Severity Index (PASI) Score

PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk and legs); each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). LS mean was calculated using ANCOVA model which includes treatment, baseline, prior biologic JIA therapy, combined JIA category and predose exposure ESR category value as fixed factors.

Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Index

The SPARCC enthesitis is an index used to measure the severity of enthesitis (sites at which tendons and ligaments attach to bones). The SPARCC assesses 16 sites for enthesitis using a score of "0" for no activity or "1" for activity. Sites assessed include Medial epicondyle (left/right [L/R]), Lateral epicondyle (L/R), Supraspinatus insertion into greater tuberosity of humerus (L/R), Greater trochanter (L/R), Quadriceps insertion into superior border of patella (L/R), Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R), Achilles tendon insertion into calcaneum (L/R), and Plantar fascia insertion into calcaneum (L/R). The SPARCC is the sum of all site scores (range 0 to 16). Higher scores indicate more severe enthesitis. LS mean was calculated using ANCOVA model which includes treatment, baseline, prior biologic JIA therapy, combined JIA category and predose exposure ESR category value as fixed factors.

Change From Baseline in Juvenile Spondyloarthritis Disease Activity (JSpADA) Index

The JSpADA index is used to evaluate the disease activity of juvenile spondyloarthritis. The JSpADA index scores will be determined by following 8 components: active joint count, active enthesitis count, pain over the past week, CRP level related to juvenile spondyloarthritis activity, morning stiffness greater than 15 minutes, clinical sacroiliitis, uveitis and back mobility. All items are transformed to values of 0, 0.5, or 1, and the total score ranges from 0 to 8, where higher scores indicate more disease activity. LS mean was calculated using ANCOVA model which includes treatment, baseline, prior biologic JIA therapy, combined JIA category and predose exposure ESR category value as fixed factors.

Pharmacokinetics (PK): Maximum Plasma Baricitinib Concentration at Steady-State (Cmax, ss)

Maximum Plasma Baricitinib Concentration at Steady-State

PK: Area Under the Baricitinib Concentration-Time Curve During a Dosing Interval at Steady-State (AUCτ,ss)

Area under the concentration-time curve of Baricitinib during a dosing interval at steady state.

Change From Baseline in Immunoglobulin Levels

Change from baseline in Serum Immunoglobulin A, Serum Immunoglobulin G and Serum Immunoglobulin M levels at week 12 are presented.

Number of Participants With Change of Immunoglobulin G (IgG) Titers

Number of participants with change of IgG titers eligible for tetanus / diphtheria / acellular pertussis (tDaP) vaccine and pneumococcal conjugate are presented. Participants who were immunized with tDaP or pneumococcal conjugate vaccine had their IgG antibody titers to the antigens evaluated preimmunization and at 4 and 12 weeks postimmunization. A primary immune response was assessed in participants who had never received tDaP or pneumococcal conjugate vaccines previously and secondary/booster responses were assessed if the participants had previously received the vaccines. For pneumococcal conjugate vaccine, number of participants with >= 2-fold increase from baseline in >=6 pneumococcal serotypes at week 4 and 12 is presented. For tDaP vaccine, number of participants with >= 4-fold increase from baseline in participants with baseline titer >=0.1 IU/mL at week 4 and 12 is presented.

Number of Participants With Product Acceptability and Palatability Assessment

The questionnaire for product acceptability and palatability assessed the participants ability to swallow the tablet, experience relating to the taste, smell and ease of administering and taking the suspension. The questionnaire contained following Questions: Question 1) How did you (your child) like the taste of the medicine? Question 2) How did you (your child) like the smell of the medicine? Question 3) How easy was it for you (your child) to take the medicine today? Question 4) How easy was it for you to use the oral syringe to give your child the dose today? and Question 5) How easy was it for you (your child) to swallow the medicine today? Responses: Liked Very Much, Liked, Neither Liked nor Disliked, Disliked, Disliked Very Much, Very Easy, Easy, Neither Easy nor Hard, Difficult (or Hard) and Very Difficult (or Hard). The number of participants with these responses are presented. Data is presented as "Question Number-Response-Time point".

Full Information

NCT ID

NCT03773978

First Posted

December 11, 2018

Last Updated

September 8, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT03773978

Brief Title

A Study of Baricitinib in Participants From 2 Years to Less Than 18 Years Old With Juvenile Idiopathic Arthritis

Acronym

JUVE-BASIS

Official 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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Completed

Study Start Date

December 17, 2018 (Actual)

Primary Completion Date

January 26, 2022 (Actual)

Study Completion Date

January 26, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The reason for this study is to see if the study drug baricitinib given orally is safe and effective in participants with JIA from 2 years to less than 18 years old.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Juvenile Idiopathic Arthritis

Keywords

Polyarticular JIA, Oligoarthritis, Juvenile psoriatic arthritis (JPsA), Enthesitis-related juvenile idiopathic arthritis (ERA)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

220 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Baricitinib

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo matched to baricitinib was administered to participants during the DBW period.

Intervention Type

Drug

Intervention Name(s)

Baricitinib

Other Intervention Name(s)

LY3009104

Intervention Description

Administered orally.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered orally.

Primary Outcome Measure Information:

Title

Time to Disease Flare

Description

Time Frame

Week 12 to Week 44

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving PedACR30 Responder Index

Description

Time Frame