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Completed

NCT Number: NCT02776735

An Open-label, Ascending, Repeated Dose-finding Study of Sarilumab in Children and Adolescents With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA)

Primary Objective:

To describe the pharmacokinetic (PK) profile of sarilumab in participants aged 2-17 years with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) in order to identify the dose and regimen for adequate treatment of this population

Secondary Objective:

To describe the pharmacodynamic (PD) profile, the efficacy and the long-term safety of sarilumab in participants with pcJIA.

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Key information

Conditions

Juvenile Idiopathic Arthritis Arthritis Arthritis, Juvenile Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

2 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Investigational Site Number : 0320060, CABA, Buenos Aires, Argentina

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About this study

For 73 participants enrolled in the dose-finding and second portions, the total study duration per participant was up to 166 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 144-week extension phase, and a 6-week post-treatment follow-up. For 29 participants enrolled in the third portion, the total study duration per participant was up to 106 weeks that consists of a 4- week screening, a 12-week core treatment phase, a 84-week extension phase, and a 6-week post-treatment follow-up.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male and female participants aged ≥2 and ≤17 years (or country specified age requirement) at the time of the screening visit.
  • Diagnosis of rheumatoid factor-negative or rheumatoid factor positive polyarticular Juvenile Idiopathic Arthritis (JIA) subtype or oligoarticular extended JIA subtype according to the International League of Associations for Rheumatology (ILAR) 2001 Juvenile Idiopathic Arthritis Classification Criteria with at least 5 active joints as per American College of Rheumatology (ACR) definition for "active arthritis" at Screening
  • Participant with an inadequate response to current treatment and considered as a candidate for a biologic disease modifying antirheumatic drug (DMARD) as per investigator's judgment

Exclusion criteria

  • Body weight <10 kg or >60 kg for participants enrolled in the 3 ascending dose cohorts, then body weight <10 kg for participants subsequently enrolled at the selected dose-regimen.
  • If nonsteroidal anti-inflammatory drugs (NSAIDs) [including cyclo oxygenase-2 inhibitors (COX-2)] taken, dose stable for <2 weeks prior to the baseline visit and/or dosing prescribed outside of approved label.
  • If non-biologic DMARD taken, dose stable for <6 weeks prior to the baseline visit or at a dose exceeding the recommended dose as per local labeling.
  • If oral glucocorticoid taken, dose exceeding equivalent prednisone dose 0.5 mg/kg/day (or 30 mg/day) within 2 weeks prior to baseline.
  • Use of parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline.
  • Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.
  • Treatment with any biologic treatment for pcJIA within 5 half-lives prior to the first dose of sarilumab.
  • Treatment with a Janus kinase inhibitor within 4 weeks prior to the first dose of sarilumab; and treatment with growth hormone within 4 weeks prior to the first dose of sarilumab (the required off treatment periods and procedures may vary according to local requirements).
  • Treatment with any investigational biologic or non-biologic product within 8 weeks or 5 half-lives prior to baseline, whichever is longer.
  • Lipid lowering drug stable for less than 6 weeks prior to screening.
  • Exclusion related to tuberculosis (TB).
  • Exclusion criteria related to past or current infection other than tuberculosis.
  • Any live, attenuated vaccine within 4 weeks prior to the baseline visit, such as varicella-zoster, oral polio, rubella vaccines. Killed or inactive vaccine may be permitted based on the Investigator's judgment.
  • Exclusion related to history of a systemic hypersensitivity reaction to any biologic drug and known hypersensitivity to any constituent of the product.
  • Laboratory abnormalities at the screening visit (identified by the central laboratory).
  • Pregnant or breast-feeding female adolescent participants.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Treatment and study plan

Sarilumab

Drug

Pharmaceutical form:Solution Route of administration: Subcutaneous

Other names: SAR153191 (REGN88)

Primary outcomes

  1. Maximum Serum Concentration (Cmax) of Sarilumab at Week 12

    Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

    The Cmax was defined as maximum serum concentration. The values reported are mean and standard deviation.

  2. Area Under the Serum Concentration Versus Time Curve Using the Trapezoidal Method During a Dose Interval (AUC0-t) of Sarilumab at Week 12

    Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

    The AUC0-t was defined as area under the concentration in serum versus time curve calculated using the trapezoidal method during a dose interval (tau). The values reported are mean and standard deviation.

  3. Concentration Before Treatment Administration During Repeated Dosing (Ctrough) of Sarilumab at Week 12

    Time frame: Pre-dose on Days 1, 3, 5, 8, 12 and Weeks 2, 4, 8 and 12

    The Ctrough was defined as concentration observed before treatment administration during repeated dosing from baseline to Week 12. The values reported are mean and standard deviation.

Secondary outcomes

  1. Cohorts 1 and 3: Change From Baseline in High-Sensitivity C-reactive Protein (Hs-CRP) at Week 12

    Time frame: Baseline (Day 1) and Week 12

    Serum concentrations of hs-CRP was determined to assess the Pharmacodynamic (PD) effects of sarilumab. The values reported are mean and standard deviation.

  2. Cohort 2: Change From Baseline in High-Sensitivity C-reactive Protein at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.

  3. Change From Baseline in Interleukin-6 (IL-6) at Week 12

    Time frame: Baseline (Day 1) and Week 12

    Serum concentrations of IL-6 was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.

  4. Change From Baseline in Total Soluble Interleukin-6 Receptor (sIL-6R) at Week 12

    Time frame: Baseline (Day 1) and Week 12

    Serum concentrations of sIL-6R was determined to assess the PD effects of sarilumab. The values reported are mean and standard deviation.

  5. Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology (JIA ACR) 30 Response at Week 12

    Time frame: Week 12

    JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 30% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  6. Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 30 Response at Weeks 12, 24, 48, 96, and 156

    Time frame: Weeks 12, 24, 48, 96, and 156

    JIA ACR30 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 30% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  7. Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Week 12

    Time frame: Week 12

    JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 50% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  8. Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 50 Response at Weeks 12, 24, 48, 96, and 156

    Time frame: Weeks 12, 24, 48, 96, and 156

    JIA ACR50 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 50% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  9. Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Week 12

    Time frame: Week 12

    JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 70% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  10. Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 70 Response at Weeks 12, 24, 48, 96, and 156

    Time frame: Weeks 12, 24, 48, 96, and 156

    JIA ACR70 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 70% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  11. Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Week 12

    Time frame: Week 12

    JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 90% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  12. Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 90 Response at Weeks 12, 24, 48, 96, and 156

    Time frame: Weeks 12, 24, 48, 96, and 156

    JIA ACR90 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 90% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  13. Cohorts 1 and 3: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Week 12

    Time frame: Week 12

    JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 100% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  14. Cohort 2: Percentage of Participants With Juvenile Idiopatic Arthritis American College of Rheumatology 100 Response at Weeks 12, 24, 48, 96, and 156

    Time frame: Weeks 12, 24, 48, 96, and 156

    JIA ACR100 response was defined as a participant with at least 3 out of the 6 JIA core set variables with >= 100% improvement from baseline with no more than 1 of the remaining variables worsened by >= 30%.

  15. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using visual analog scale (VAS), Childhood Health Questionnaire Disability Index (CHAQ-DI) and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)*(71/number of joints with assessment).

  16. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Activity Joint Count-71, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Activity joint count-71 was calculated as sum (joints with active arthritis)*(71/number of joints with assessment).

  17. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)*(67/number of joints with assessment).

  18. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Limited Motion Joint Count, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Limited motion joint count was calculated as sum (joints with limited motion)*(67/number of joints with assessment).

  19. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of "not applicable" is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome.

  20. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Childhood Health Assessment Questionnaire Disability Index, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. The CHAQ questionnaire consists of 30 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities. Each domain is scored on a 4 point scale ranges from 0 to 3: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). An additional response of "not applicable" is available to indicate activities the participant is unable to perform because he/she is too young. The CHAQ-DI total score is the sum of the domain scores divided by the number of domains that have a non-missing score. This overall score ranges from 0 (best) to 3 (worst). Higher scores indicate worse outcome.

  21. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab.

  22. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, C-Reactive Protein, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Serum concentrations of hs-CRP was determined to assess the PD effects of sarilumab.

  23. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.

  24. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Physician Global Assessment of Disease Activity, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Physician global assessment of disease activity was assessed on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.

  25. Cohorts 1 and 3: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.

  26. Cohort 2: Change From Baseline in Juvenile Idiopatic Arthritis American College of Rheumatology Component, Participant/Parent Assessment of Overall Well-Being, at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JIA ACR components included joints with active arthritis (0 to 71 joints), joints with limited motion (0 to 67 joints), physician global assessment of disease activity and participant/parent assessment of overall well-being using VAS, CHAQ-DI and hs-CRP. Participant/parent assessment of overall well-being was rated on an anchored 100 mm horizontal VAS score ranging from 0 to 10 where 0 is considered the best disease activity (no disease activity) and 10 the worst (most disease activity). Higher scores indicate worse outcome.

  27. Cohorts 1 and 3: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score (JADAS-27) at Week 12

    Time frame: Baseline (Day 1) and Week 12

    The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity.

  28. Cohort 2: Mean Change From Baseline in Juvenile Arthritis Disease Activity Score at Weeks 12, 24, 48, 96, and 156

    Time frame: Baseline (Day 1) and Weeks 12, 24, 48, 96, and 156

    The JADAS is used for assessment of disease activity, and it includes 4 measures: Physician global assessment of disease activity (VAS range: 0 to10; where 0= no activity and 10= maximum activity), parent/participant global assessment of well-being (VAS range: 0 to 10; where 0= no activity and10= maximum activity), count of joints with active disease (range: 0 to 27; where 0= no activity and 27= maximum activity), and index of inflammation determined by hs-CRP or ESR (normalized scale range: 0 to 10; where 0= no disease activity and 10= maximum disease activity). The JADAS total score is calculated as the simple sum of the scores of its 4 components. The total score ranges from 0 to 57 where 0= no disease activity and 57= maximum disease activity. Higher scores indicate higher disease activity. Clinical JADAS-27 is without CRP or ESR component and score ranges from 0 to 47 where 0= no disease activity and 47= maximum disease activity.

  29. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)

    Time frame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3

    An adverse events (AEs) is any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with the study treatment. An SAE is any untoward medical occurrence that at any dose results in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity or is a congenital anomaly/birth defect or is an important medical event. TEAEs are defined as AEs that develop or worsen during the on-treatment period [that is, from the time of first dose of study treatment up to 6 weeks after the last administration of the study treatment].

  30. Number of Participants With Local Site Reactions

    Time frame: From the first administration of study treatment (Day 1) up to end of treatment period, maximum of 156 weeks for portions 1 and 2 and 96 weeks for portion 3

    Participants were observed for at least 30 minutes after each study treatment administration either on site or at home and any local reactions were noted in the diary regardless of being clinically significant.

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Collaborators

  • Regeneron Pharmaceuticals

Registry information

Official study title

An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered With Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, With Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase

Acronym: SKYPP

Important dates

Study start
2016
Primary completion
2022
Study completion
2023
First posted
May 18, 2016
Registry last updated
Oct 15, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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