A Study of Baricitinib in Participants From 2 Years to Less Than 18 Years Old With Juvenile Idiopathic Arthritis
- Registration Number
- NCT03773978
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo matched to baricitinib was administered to participants during the DBW period. Baricitinib Baricitinib 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.
- Primary Outcome Measures
Name Time Method Time to Disease Flare Week 12 to Week 44 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
Name Time Method Percentage of Participants Achieving PedACR30 Responder Index Week 16, 20, 24, 28, 32, 36, 40 and 44 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 in Remission Week 28, 32, 36, 40 and 44 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 Baseline, Week 44 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.
Percentage of Participants Achieving PedACR90 Responder Index Week 16, 20, 24, 28, 32, 36, 40 and 44 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 With Minimal Disease Activity Week 16, 20, 24, 28, 32, 36, 40 and 44 Minimal disease activity is calculated based on the scores from the
1. Physician's Global Assessment of Disease Activity
2. Parent's Global Assessment of Well-Being and
3. 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 With Inactive Disease Week 16, 20, 24, 28, 32, 36, 40 and 44 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 (Score ranges are 0 to 100 and best possible score on scale is 0) and
6. Duration of morning stiffness ≤15 minutes.Number of Participants With Change of Immunoglobulin G (IgG) Titers Pre-Vaccination to 4 and 12 Weeks Post-Vaccination 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.
Percentage of Participants Achieving PedACR50 Responder Index Week 16, 20, 24, 28, 32, 36, 40 and 44 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.
PK: Area Under the Baricitinib Concentration-Time Curve During a Dosing Interval at Steady-State (AUCτ,ss) For Safety/PK period: Day 1, Day 4, Day 14 (pre dose) and Day 14 (post dose). For OLLI period: Day 1, Day 14, Day 28, Day 56 and 84 (pre dose) Area under the concentration-time curve of Baricitinib during a dosing interval at steady state.
Percentage of Participants Achieving PedACR70 Responder Index Week 16, 20, 24, 28, 32, 36, 40 and 44 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 PedACR100 Responder Index Week 16, 20, 24, 28, 32, 36, 40 and 44 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.
Change From Baseline in Arthritis-Related Pain Severity as Measured by the Childhood Health Assessment Questionnaire (CHAQ) Pain Visual Analog Scale (VAS) Item Baseline, Week 44 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.
Pharmacokinetics (PK): Maximum Plasma Baricitinib Concentration at Steady-State (Cmax, ss) For Safety/PK period: Day 1, Day 4, Day 14 (pre dose) and Day 14 (post dose). For OLLI period: Day 1, Day 14, Day 28, Day 56 and 84 (pre dose) Maximum Plasma Baricitinib Concentration at Steady-State
Number of Participants With Product Acceptability and Palatability Assessment Baseline and week 12 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".
Change From Baseline in Immunoglobulin Levels Baseline, Week 12 Change from baseline in Serum Immunoglobulin A, Serum Immunoglobulin G and Serum Immunoglobulin M levels at week 12 are presented.
Change From Baseline in Psoriasis Area and Severity Index (PASI) Score Baseline, Week 44 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 Baseline, Week 44 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 Baseline, Week 44 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.
Trial Locations
- Locations (86)
Children's Hospital of Soochow University
🇨🇳Suzhou, China
Royal Childrens Hospital Melbourne
🇦🇺Parkville, Victoria, Australia
Centro Medico Privado de Reumatologia
🇦🇷SAN M. DE Tucuman, Tucumán, Argentina
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Hospital General de Niños Dr. Pedro de Elizalde
🇦🇷Buenos Aires, Argentina
Schneider Children's Medical Center
🇮🇱Petah Tiqva, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
LKH Bregenz
🇦🇹Bregenz, Vorarlberg, Austria
Osaka Medical ＆ Pharma Univ Hp
🇯🇵Takatsuki, Osaka, Japan
Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
CMIP - Centro Mineiro de Pesquisa
🇧🇷Juiz de Fora, Minas Gerais, Brazil
AKH
🇦🇹Wien, Austria
UZ Gent-Reuma
🇧🇪Gent, East Flanders, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Children's hospital of Nanjing
🇨🇳Nanjing, Jiangsu, China
Faculdade de Medicina de Botucatu
🇧🇷Botucatu, Sao Paulo, Brazil
Capitol Institute of Pediatrics Children'S Hospital
🇨🇳Beijing, China
Universidade Federal de São Paulo - Escola Paulista de Medicina
🇧🇷São Paulo, Brazil
Faculdade de Ciências Médicas - UNICAMP
🇧🇷Campinas, Sao Paulo, Brazil
Children's Hospital of Chongqing Medical University
🇨🇳Chongqing, Tianjin City, China
Centrum detske revmatologie VFN, Klinika detskeho a dorostoveho lekarstvi 1.LFUK a VFN v Praze
🇨🇿Prague, Czechia
Paediatric rheumatology Unit
🇩🇰København Ø, Denmark
Fakultni Nemocnice v Motole
🇨🇿Praha 5, Czechia
Centre Hospitalier Universitaire de Nîmes - Hôpital Universitaire Carémeau
🇫🇷Nîmes, France
Universitätsklinikum Tübingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Hospices Civils de Lyon - Hôpital Femme Mère Enfant
🇫🇷Bron, France
Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre
🇫🇷Le Kremlin Bicetre, France
GH Necker - Enfants Malades
🇫🇷Paris Cedex 15, France
CHU la Miletrie
🇫🇷Poitiers, France
Asklepios Klinik Sankt Augustin
🇩🇪Saint Augustin, Nordrhein-Westfalen, Germany
HELIOS Klinikum Berlin-Buch
🇩🇪Berlin, Germany
Schön Klinik Hamburg Eilbek
🇩🇪Hamburg, Germany
Sri Ramachandra MedicaL College & Research Institute
🇮🇳Porur, Chennai, India
Sir Ganga Ram Hospital
🇮🇳New Delhi, Delhi, India
Christian Medical College Vellore
🇮🇳Vellore, Tamil Nadu, India
Meir Medical Center
🇮🇱Kfar Saba, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Azienda Ospedaliero Universitaria Meyer
🇮🇹Firenze, Italy
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Federico II
🇮🇹Napoli, Italy
Ospedale Infantile Burlo Garofolo
🇮🇹Trieste, Italy
Kanagawa Children's Medical Center
🇯🇵Yokohama, Kanagawa, Japan
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
Miyagi Children's Hospital
🇯🇵Sendai, Miyagi, Japan
Saitama Children's Medical Center
🇯🇵Saitama-shi, Saitama, Japan
St. Lukes International Hospital
🇯🇵Chuo-Ku, Tokyo, Japan
Tokyo Medical And Dental University Medical Hospital
🇯🇵Bunkyō, Tokyo, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Clinstile, S.A. de C.V.
🇲🇽Cuauhtemoc, Federal District, Mexico
Hospital Univ. "Dr. José Eleuterio González"
🇲🇽Monterrey, Nuevo León, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia A.C
🇲🇽Durango, Mexico
CREA de Guadalajara, S.C.
🇲🇽Guadalajara, Jalisco, Mexico
Investigacion y Biomedicina de Chihuahua
🇲🇽Chihuahua, Mexico
Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie
🇵🇱Krakow, Poland
CSK, Uniwersyteckie Centrum Pediatrii im.M.Konopnickiej,Klinika Kardiologii i Reumatologii Dzieciecej
🇵🇱Lodz, Poland
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji
🇵🇱Warszawa, Poland
Morozovsky Children's City Clinical Hospital
🇷🇺Moscow, Russian Federation
First Moscow State Medical University n.a. Sechenov
🇷🇺Moscow, Russian Federation
V.A. Nasonova Research Institute of Rheumatology
🇷🇺Moscow, Russian Federation
Scientific Center of Children's Health
🇷🇺Moscow, Russian Federation
Saint-Petersburg State Pediatric Medical University
🇷🇺Saint Petersburg, Russian Federation
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Spain
Hospital Sant Joan de Deu
🇪🇸Barcelona, Cataluna, Spain
Complexo Hospitalario Universitario A Coruña, CHUAC
🇪🇸La Coruña, Spain
Dokuz Eylul University Hospital
🇹🇷Izmir, Turkey
Hospital Universitario La Fe de Valencia
🇪🇸Valencia, Spain
Istanbul University Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Great Ormond Street Hospital For Children NHS Foundation Trust
🇬🇧Bloomsbury, London, United Kingdom
Sheffield Children's Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
University College Hospital - London
🇬🇧London, Greater London, United Kingdom
Alder Hey Children's NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
The Sydney Children's Hospitals Network
🇦🇺Westmead, New South Wales, Australia
Charité Universitätsmedizin Berlin Campus Buch
🇩🇪Berlin, Germany
Instituto CAICI SRL
🇦🇷Rosario, Santa Fe, Argentina
UCL- Saint Luc
🇧🇪Brussels, Brussels-Capital, Belgium
Beijing Children's hospital, Capital Medical University
🇨🇳Beijing, China
Center for Børnereumatologi. Børn og Unge, Århus Universitetshospital
🇩🇰Århus N, Denmark
ASST Spedali Civili - Università degli Studi
🇮🇹Brescia, Italy
Ospedale SS. Annunziata
🇮🇹Chieti, Italy
Ospedale Pediatrico Gaslini - Istituto Giannina Gaslini
🇮🇹Genova, Italy
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata, Japan