Secukinumab Safety and Efficacy in Juvenile Psoriatic Arthritis (JPsA) and Enthesitis-related Arthritis (ERA)
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| ClinicalTrials.gov Identifier: NCT03031782 |
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Recruitment Status :
Completed
First Posted : January 26, 2017
Results First Posted : August 15, 2022
Last Update Posted : August 15, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Juvenile Psoriatic Arthritis Enthesitis-related Arthritis | Drug: secukinumab Other: placebo | Phase 3 |
TP1: All eligible subjects entered TP1 to receive 12-weeks of open-label secukinumab at a dose predicted to achieve secukinumab serum levels equivalent to adults administered a 150 mg dose regimen. Secukinumab was administered s.c. weekly for the first 4 weeks (Baseline, Weeks 1, 2, 3, 4) and then every 4 weeks thereafter. Clinical response (JIA ACR 30) was assessed at Week 12. Responders advanced to TP2 and non-responders exited the trial (early termination visit and entered into the Post-treatment follow-up period).
TP2: Subjects who were a responder (JIA ACR 30) at Week 12 entered the double-blind withdrawal TP2 and were randomized 1:1 to either secukinumab or placebo on that visit and then every 4 weeks, until either experiencing a disease flare or completion of TP2. TP2 was event driven and was planned to be closed when 33 subjects experienced a disease flare as per JIA definition. Alternatively, the study could be closed when all subjects reached the total study duration of 104 Weeks and therefore subjects who did not experience a disease flare remained in TP2 for the duration of the study and completed the study without entering into TP3
TP3: Subjects experiencing a disease flare in TP2 immediately entered TP3 to receive openlabel secukinumab every 4 weeks until total study duration of 104 weeks for that subject was achieved.
Post-treatment follow-up: The post-treatment follow-up period (lasting 12 weeks from the last study drug administration) was required for all subjects, unless they qualified and entered the secukinumab extension trial. All subjects were expected to participate in the post-treatment follow up period, except for those entering the extension study.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 86 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Three-part Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Secukinumab Treatment in Juvenile Idiopathic Arthritis Subtypes of Psoriatic and Enthesitis-related Arthritis |
| Actual Study Start Date : | May 23, 2017 |
| Actual Primary Completion Date : | October 7, 2020 |
| Actual Study Completion Date : | November 9, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment Period 2 - active
secukinumab (AIN457 - pre-filled syringe) for patients with a minimum American college of Rheumatology (ACR) 30 response in Treatment Period 1
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Drug: secukinumab
secukinumab is a high-affinity fully human monoclonal anti-human antibody that targets IL-17A and neutralizes activity.
Other Name: AIN457 |
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Placebo Comparator: Treatment Period 2 - placebo
placebo comparator (matched to secukinumab treatment) for patients with a minimum American college of Rheumatology (ACR) 30 response in Treatment Period 1
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Other: placebo
Matched placebo to AIN457 for use in the double blind Treatment Period 2 |
- Number of Participants Experiencing a Flare During Treatment Period 2 [ Time Frame: From Week 12 until max Week 104 ]
Survival analysis of time to flare in treatment period 2 (TP2) FAS2
Subjects are either ERA or JPsA
- Percent of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90/100 Response at Week 12 - by JIA Category [ Time Frame: baseline, week 12 ]
Summary of JIA ACR 30/50/70/90/100 for all subjects and each JIA category - TP1 (FAS1)
The adapted ACR Pediatric 30/50/70/90/100 criteria was used to determine efficacy defined as improvement from baseline of at least 30/50/70/90/100% respectively in at least 3 of the following 6 components
- Physician's Global Assessment of disease activity on a 0-100 mm VAS from 0 mm = no disease activity to 100 mm = very severe disease activity.
- Parent's or patient's Global Assessment of Subject's overall wellbeing on a 0-100 mm VAS from 0 mm= very well to 100 mm= very poor.
- Functional ability: Childhood Health Assessment Questionnaire (CHAQ©)
- Number of joints with active arthritis using the ACR definition (The ACR definition of active arthritis is any joint with swelling, or in the absence of swelling, limitation of motion accompanied by either pain on motion or tenderness not due to deformity)
- Number of joints with limitation of motion
- Laboratory measure of inflammation: CRP (mg/L)
- Percent of Participants With Juvenile Idiopathic Arthritis (JIA) American College of Rheumatology (ACR) 30/50/70/90/100 Response at Week 12 - Total [ Time Frame: baseline, week 12 ]
Summary of JIA ACR 30/50/70/90/100 for all subjects - TP1 (FAS1)
The adapted ACR Pediatric 30/50/70/90/100 criteria was used to determine efficacy defined as improvement from baseline of at least 30/50/70/90/100% respectively in at least 3 of the following 6 components
- Physician's Global Assessment of disease activity on a 0-100 mm VAS from 0 mm = no disease activity to 100 mm = very severe disease activity.
- Parent's or patient's Global Assessment of Subject's overall wellbeing on a 0-100 mm VAS from 0 mm= very well to 100 mm= very poor.
- Functional ability: Childhood Health Assessment Questionnaire (CHAQ©)
- Number of joints with active arthritis using the ACR definition (The ACR definition of active arthritis is any joint with swelling, or in the absence of swelling, limitation of motion accompanied by either pain on motion or tenderness not due to deformity)
- Number of joints with limitation of motion
- Laboratory measure of inflammation: CRP (mg/L)
- Percent Change From Baseline for JIA ACR Core Components in TP1 [ Time Frame: baseline, week 12 ]
Summary of JIA ACR core components for all subjects and each JIA category - Treatment period 1
Negative percent change indicates improvement
Physician global assessment of disease activity (VAS mm) 0 (no disease activity) - 100 (very severe); Parent or subject global assessment of overall well-being (VAS mm) 0 (very well) - 100 (very poor); CHAQ (Childhood Health Assessment Questionnaire) 0 - 3 (most severe); Number of joints with active arthritis 0 - 73; Number of joints with limited range of motion 0 - 69.
- Percent Change in C-reactive Protein Standardized Value (mg/L) [ Time Frame: baseline, week 12 ]Median Percent Change from baseline for C-reactive protein standardized value (mg/L)
- Change From Baseline Juvenile Arthritis Disease Activity Score (JADAS) Score [ Time Frame: 12 weeks ]JADAS change from baseline for all subjects in Treatment period 1. JADAS-27 (Juvenile Arthritis Disease Activity Score in 27 joints) ranges from 0 to 57 and JADAS-71 ranges from 0 to 101 (higher scores indicate more disease activity).
- Change From Baseline in Total Enthesitis Events - TP1 (FAS1) [ Time Frame: Baseline and week 12 ]
Enthesitis swollen joint count range is 0-16. Zero is worst, and 16 is best
A total of 16 entheseal sites were assessed for the presence or absence of tenderness of enthesitis.
This is the mean (SD) enthesitis count (range 0-16) for FAS subjects
A zero score means no enthesitis, so a zero score is better for the patient
- Change From Baseline in Total Dactylitis Count [ Time Frame: baseline, week 12 ]
Summary of total dactylitis count for all subjects - TP1 (FAS1)
Total dactylitis count ranges from 0 to 20. A zero score means no dactylitis, so a zero score is better for the patient
- Number of Participants With Anti-secukinumab Anitbodies [ Time Frame: 104 weeks ]Blood samples for immunogenicity (anti-AIN457 antibodies) were taken pre-dose at the scheduled time points. In addition, if a subject discontinued from the study at any time, he/she provided a sample at the last visit. All blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein. An Electrochemiluminescence method was used for the detection of potential anti-secukinumab antibody formation.
- Secukinumab Serum Concentration [ Time Frame: baseline, week 12 ]Summary of pharmacokinetic concentrations - Treatment period 1
- Number of Participants With Inactive Disease Status for All Subjects - TP1 (FAS1) [ Time Frame: week 12 ]
Summary of inactive disease status for all subjects - TP1 (FAS1)
Clinical inactive disease definition was adapted from the JIA ACR criteria.
All were required to be met:
- No joints with active arthritis
- No uveitis
- CRP value within normal limits for the laboratory where tested or, if elevated, not attributable to JIA
- Physician's global assessment of disease activity score ≤ 10mm
- Duration of morning stiffness attributable to JIA ≤15 min
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| Ages Eligible for Study: | 2 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Confirmed diagnosis of Enthesitis-related arthritis (ERA) or Juvenile psoriatic arthritis (JPsA) according to the International League of Associations for Rheumatology (ILAR) classification criteria of at least 6 months duration.
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Active disease (ERA or JPsA) defined as having both:
- at least 3 active joints
- at least 1 site of active enthesitis at baseline or documented by history.
- Inadequate response (at least 1 month) or intolerance to at least 1 nonsteroidal anti-inflammatory drugs(NSAID)
- Inadequate response (at least 2 months) or intolerance to at least 1 Disease-modifying antirheumatic drugs (DMARD)
- No concomitant use of second line agents such as disease-modifying and/or immunosuppressive drugs.
Exclusion Criteria:
- Patients fulfilling any ILAR diagnostic JIA category other than ERA or JPsA.
- Patients who have ever received biologic immunomodulating agents
- Patients taking any non-biologic DMARD except for MTX (or sulfasalazine for ERA patients only).
- Patients with active uncontrolled inflammatory bowel disease or active uncontrolled uveitis.
Other protocol-defined inclusion/exclusion criteria apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03031782
| United States, California | |
| Novartis Investigative Site | |
| Los Angeles, California, United States, 90027 | |
| United States, Idaho | |
| Novartis Investigative Site | |
| Boise, Idaho, United States, 83702 | |
| United States, Ohio | |
| Novartis Investigative Site | |
| Cincinnati, Ohio, United States, 45229 | |
| United States, Oregon | |
| Novartis Investigative Site | |
| Portland, Oregon, United States, 97232 | |
| Belgium | |
| Novartis Investigative Site | |
| Bruxelles, Belgium, 1200 | |
| Novartis Investigative Site | |
| Gent, Belgium, 9000 | |
| Novartis Investigative Site | |
| Laeken, Belgium, 1020 | |
| Germany | |
| Novartis Investigative Site | |
| Berlin, Germany, 13353 | |
| Novartis Investigative Site | |
| Freiburg, Germany, 79106 | |
| Novartis Investigative Site | |
| Hamburg, Germany, 22081 | |
| Novartis Investigative Site | |
| Saint Augustin, Germany, 53757 | |
| Italy | |
| Novartis Investigative Site | |
| Genova, GE, Italy, 16147 | |
| Novartis Investigative Site | |
| Napoli, Italy, 80131 | |
| Poland | |
| Novartis Investigative Site | |
| Krakow, Poland, 31503 | |
| Russian Federation | |
| Novartis Investigative Site | |
| Ekaterinburg, Russian Federation, 620149 | |
| Novartis Investigative Site | |
| Moscow, Russian Federation, 119991 | |
| Novartis Investigative Site | |
| Saint-Petersburg, Russian Federation, 194100 | |
| Novartis Investigative Site | |
| Voronezh, Russian Federation, 394036 | |
| South Africa | |
| Novartis Investigative Site | |
| Cape Town, South Africa, 7925 | |
| Novartis Investigative Site | |
| Panorama, South Africa, 7500 | |
| Spain | |
| Novartis Investigative Site | |
| Santiago de Compostela, Galicia, Spain, 15706 | |
| Novartis Investigative Site | |
| Valencia, Spain, 46026 | |
| Turkey | |
| Novartis Investigative Site | |
| Istanbul, Halkali, Turkey, 34303 | |
| Novartis Investigative Site | |
| Istanbul, TUR, Turkey, 34098 | |
| Novartis Investigative Site | |
| Ankara, Turkey, 06100 | |
| Novartis Investigative Site | |
| Istanbul, Turkey, 34766 | |
| United Kingdom | |
| Novartis Investigative Site | |
| Bristol, United Kingdom, BS2 8BJ | |
| Novartis Investigative Site | |
| Glasgow, United Kingdom, G51 4TF | |
| Novartis Investigative Site | |
| Liverpool, United Kingdom, L12 2AP | |
| Novartis Investigative Site | |
| London, United Kingdom, WC1N 3JH | |
| Novartis Investigative Site | |
| Nottingham, United Kingdom, NG7 2UH | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03031782 |
| Other Study ID Numbers: |
CAIN457F2304 2016-003761-26 ( EudraCT Number ) |
| First Posted: | January 26, 2017 Key Record Dates |
| Results First Posted: | August 15, 2022 |
| Last Update Posted: | August 15, 2022 |
| Last Verified: | August 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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JIA JPsA ERA |
Secukinumab ILAR Arthritis |
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Arthritis Arthritis, Psoriatic Enthesopathy Arthritis, Juvenile Joint Diseases Musculoskeletal Diseases Spondylarthropathies Spondylarthritis Spondylitis Spinal Diseases Bone Diseases |
Psoriasis Skin Diseases, Papulosquamous Skin Diseases Tendinopathy Muscular Diseases Tendon Injuries Wounds and Injuries Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases |