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

Juvenile Idiopathic Arthritis Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03773978
• Other study ID #: 16276
• Secondary ID: I4V-MC-JAHV2017-
• Status: Completed
• Phase: Phase 3
• Start date: December 17, 2018
• Est. completion date: January 26, 2022

Study information

• Verified date: September 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: January 26, 2022
• Est. primary completion date: January 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Juvenile
• Juvenile Idiopathic Arthritis

Intervention

Drug:
• Baricitinib
Administered orally.
• Placebo
Administered orally.

Locations

Country	Name	City	State
Argentina	Hospital General de Niños Dr. Pedro de Elizalde	Buenos Aires
Argentina	Instituto CAICI SRL	Rosario	Santa Fe
Argentina	Centro Medico Privado de Reumatologia	SAN M. DE Tucuman	Tucumán
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	Royal Childrens Hospital Melbourne	Parkville	Victoria
Australia	The Sydney Children's Hospitals Network	Westmead	New South Wales
Austria	LKH Bregenz	Bregenz	Vorarlberg
Austria	AKH	Wien
Belgium	UCL- Saint Luc	Brussels	Brussels-Capital
Belgium	UZ Gent-Reuma	Gent	East Flanders
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Brazil	Faculdade de Medicina de Botucatu	Botucatu	Sao Paulo
Brazil	Faculdade de Ciências Médicas - UNICAMP	Campinas	Sao Paulo
Brazil	CMIP - Centro Mineiro de Pesquisa	Juiz de Fora	Minas Gerais
Brazil	Universidade Federal de São Paulo - Escola Paulista de Medicina	São Paulo
China	Beijing Children's hospital, Capital Medical University	Beijing
China	Capitol Institute of Pediatrics Children'S Hospital	Beijing
China	Children's Hospital of Chongqing Medical University	Chongqing	Tianjin City
China	Children's hospital of Nanjing	Nanjing	Jiangsu
China	Children's Hospital of Soochow University	Suzhou
Czechia	Centrum detske revmatologie VFN, Klinika detskeho a dorostoveho lekarstvi 1.LFUK a VFN v Praze	Prague
Czechia	Fakultni Nemocnice v Motole	Praha 5
Denmark	Center for Børnereumatologi. Børn og Unge, Århus Universitetshospital	Århus N
Denmark	Paediatric rheumatology Unit	København Ø
France	Hospices Civils de Lyon - Hôpital Femme Mère Enfant	Bron
France	Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre	Le Kremlin Bicetre
France	Centre Hospitalier Universitaire de Nîmes - Hôpital Universitaire Carémeau	Nîmes
France	GH Necker - Enfants Malades	Paris Cedex 15
France	CHU la Miletrie	Poitiers
Germany	Charité Universitätsmedizin Berlin Campus Buch	Berlin
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	Schön Klinik Hamburg Eilbek	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Asklepios Klinik Sankt Augustin	Saint Augustin	Nordrhein-Westfalen
Germany	Universitätsklinikum Tübingen	Tübingen	Baden-Württemberg
India	Sir Ganga Ram Hospital	New Delhi	Delhi
India	Sri Ramachandra MedicaL College & Research Institute	Porur	Chennai
India	Christian Medical College Vellore	Vellore	Tamil Nadu
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Schneider Children's Medical Center	Petah Tiqva
Israel	Sheba Medical Center	Ramat Gan
Italy	ASST Spedali Civili - Università degli Studi	Brescia
Italy	Ospedale SS. Annunziata	Chieti
Italy	Azienda Ospedaliero Universitaria Meyer	Firenze
Italy	Ospedale Pediatrico Gaslini - Istituto Giannina Gaslini	Genova
Italy	Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Ospedale Infantile Burlo Garofolo	Trieste
Japan	Tokyo Medical And Dental University Medical Hospital	Bunkyo	Tokyo
Japan	St. Lukes International Hospital	Chuo-Ku	Tokyo
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kanazawa University Hospital	Kanazawa	Ishikawa
Japan	Niigata University Medical & Dental Hospital	Niigata
Japan	Saitama Children's Medical Center	Saitama-shi	Saitama
Japan	Miyagi Children's Hospital	Sendai	Miyagi
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	Osaka Medical & Pharma Univ Hp	Takatsuki	Osaka
Japan	Kanagawa Children's Medical Center	Yokohama	Kanagawa
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Mexico	Investigacion y Biomedicina de Chihuahua	Chihuahua
Mexico	Clinstile, S.A. de C.V.	Cuauhtemoc	Federal District
Mexico	Instituto de Investigaciones Aplicadas a la Neurociencia A.C	Durango
Mexico	CREA de Guadalajara, S.C.	Guadalajara	Jalisco
Mexico	Hospital Univ. "Dr. José Eleuterio González"	Monterrey	Nuevo León
Poland	Wojewódzki Specjalistyczny Szpital Dzieciecy im. sw. 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
Russian Federation	First Moscow State Medical University n.a. Sechenov	Moscow
Russian Federation	Morozovsky Children's City Clinical Hospital	Moscow
Russian Federation	Scientific Center of Children's Health	Moscow
Russian Federation	V.A. Nasonova Research Institute of Rheumatology	Moscow
Russian Federation	Saint-Petersburg State Pediatric Medical University	Saint Petersburg
Spain	Hospital Sant Joan de Deu	Barcelona	Cataluna
Spain	Complexo Hospitalario Universitario A Coruña, CHUAC	La Coruña
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario La Fe de Valencia	Valencia
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Dokuz Eylul University Hospital	Izmir
United Kingdom	Great Ormond Street Hospital For Children NHS Foundation Trust	Bloomsbury	London
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
United Kingdom	University College Hospital - London	London	Greater London
United Kingdom	Sheffield Children's Hospital	Sheffield	South Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 12 to Week 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 16, 20, 24, 28, 32, 36, 40 and 44
Secondary	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.	Week 28, 32, 36, 40 and 44
Secondary	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.	Baseline, Week 44
Secondary	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.	Baseline, Week 44
Secondary	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.	Baseline, Week 44
Secondary	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.	Baseline, Week 44
Secondary	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.	Baseline, Week 44
Secondary	Pharmacokinetics (PK): Maximum Plasma Baricitinib Concentration at Steady-State (Cmax, ss)	Maximum Plasma Baricitinib Concentration at Steady-State	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)
Secondary	PK: Area Under the Baricitinib Concentration-Time Curve During a Dosing Interval at Steady-State (AUCt,ss)	Area under the concentration-time curve of Baricitinib during a dosing interval at steady state.	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)
Secondary	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.	Baseline, Week 12
Secondary	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.	Pre-Vaccination to 4 and 12 Weeks Post-Vaccination
Secondary	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".	Baseline and week 12

External Links

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