Upadacitinib + Tocilizumab for Juvenile Idiopathic Arthritis

(SELECT-sJIA Trial)

Recruiting in Palo Alto (17 mi)

+46 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AbbVie

Must not be taking: IL-6 inhibitors

Disqualifiers: Other JIA, Autoimmune conditions, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Juvenile Idiopathic Arthritis (JIA) is the most common type of arthritis that affects children. The term "idiopathic" means "of unknown origin". It is a chronic (long-lasting) disease that causes swelling, warmth, and pain of one or more small joints. Systemic JIA ia a rare and serious form of JIA. Systemic" means it may affect not only the joints but other parts of the body, including the liver, lungs and heart. sJIA is more severe and can be more challenging to diagnose and treat than other types of juvenile idiopathic arthritis. It is a lifelong disease for many patients and can continue into adulthood. This study will assess how safe and effective upadacitinib is in treating pediatric and adolescent participants aged 1 to \< 18 with systemic juvenile idiopathic arthritis (sJIA) and will include a tocilizumab treatment arm for reference. Adverse events and change in the disease activity will be assessed. Upadacitinib is an investigational drug being developed for the treatment of sJIA. Participants are assigned to 1 of 2 cohorts. In cohort 1, participants will receive upadacitinib or tocilizumab reference. In cohort 2, participants will receive upadacitinib. Approximately 90 participants with sJIA will be enrolled in approximately 45 sites worldwide. Participants will receive upadacitinib oral tablets once daily or oral solution twice daily or tocilizumab subcutaneous injection or intravenous infusion as per local label for 52 weeks and followed for approximately 30 days. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits/calls during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have an inadequate response to previous treatments, which might imply some changes to your current medication regimen. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug Tocilizumab for treating juvenile idiopathic arthritis?

Research shows that Tocilizumab is effective in treating juvenile idiopathic arthritis, as it helps reduce symptoms in children with both polyarticular-course and systemic-onset forms of the disease.

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Is the combination of Upadacitinib and Tocilizumab safe for treating juvenile idiopathic arthritis?

Tocilizumab has been studied for safety in treating juvenile idiopathic arthritis, showing it is generally safe but can have side effects like serious infections. Long-term safety data from Japan also supports its use, though monitoring for side effects is important.

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How is the drug combination of Upadacitinib and Tocilizumab unique for treating juvenile idiopathic arthritis?

The combination of Upadacitinib and Tocilizumab is unique because it targets different pathways involved in inflammation: Upadacitinib is a JAK inhibitor (a type of drug that blocks certain enzymes involved in inflammation), while Tocilizumab is an anti-interleukin-6-receptor monoclonal antibody (a drug that blocks a specific protein involved in the immune response). This dual approach may offer a new option for patients who do not respond to existing treatments.

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Eligibility Criteria

This trial is for children and adolescents aged 1 to <18 with systemic juvenile idiopathic arthritis (sJIA). They must have at least 2 active joints, fever over 38°C, or elevated inflammation markers. Participants in Cohort 1 can't have had IL-6 inhibitor treatment; those in Cohort 2 must not respond well to it.

Inclusion Criteria

My previous treatments with anti-inflammatory drugs and steroids didn't work well.

I am between 2 and 17 years old and live where SC tocilizumab is not approved for sJIA.

For Cohort 1, participants must not have had previous treatment with any IL-6 inhibitor. For Cohort 2, participants must have an intolerance or inadequate response to an IL-6 inhibitor as judged by the investigator

Exclusion Criteria

I have juvenile idiopathic arthritis but not the systemic kind.

I have a severe illness or a condition related to immune system overactivity in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive upadacitinib or tocilizumab for 52 weeks

52 weeks

Regular visits/calls at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests the safety and effectiveness of Upadacitinib, an oral medication, against Tocilizumab, given as a subcutaneous injection or intravenous infusion. About 90 participants will be randomly assigned to receive one of these treatments for a year.

Group I: Cohort 2 Upadacitinib Experimental Treatment 1 Intervention

Participants will receive upadacitinib for 52 weeks.

Group II: Cohort 1 Upadacitinib Experimental Treatment 1 Intervention

Participants will receive upadacitinib for 52 weeks.

Group III: Cohort 1 Tocilizumab Active Control 1 Intervention

Participants will receive tocilizumab for 52 weeks.

Tocilizumab is already approved in European Union, United States, Canada, Japan, Australia for the following indications:

🇪🇺 Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

🇺🇸 Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

🇨🇦 Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

🇯🇵 Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

🇦🇺 Approved in Australia as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

New York Medical College /ID# 253437 Valhalla, NY

Levine Children's Hospital /ID# 253491 Charlotte, NC

Randall Children's Hospital /ID# 251829 Portland, OR

Who Is Running the Clinical Trial?

AbbVie Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial. [2021] To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA).

2. United States pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of juvenile idiopathic arthritis. [2016] To evaluate the pharmacology, clinical efficacy, safety, and role of tocilizumab for the treatment of juvenile idiopathic arthritis.

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. [2022] Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder.

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. [2022] To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

5. Canada pubmed.ncbi.nlm.nih.gov

Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic Arthritis: 2-year Data from a Phase III Clinical Trial. [2019] Evaluate growth in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ) for up to 2 years in a phase III trial.

6. England pubmed.ncbi.nlm.nih.gov

What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis? [2022] This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication, very common side effects, expected time of response and average cost in the first year). The emphasis of this review is on the immunological side effects that have been encountered for every separate agent in JIA populations. For each agent these adverse events have been calculated as incidence per 100 patient-years for the following categories: serious infections, tuberculosis, malignancies, response to vaccination, new-onset autoimmune diseases and development of anti-drug antibodies. There are large differences in side effects between various agents and there is a clear need for an international and standardized collection of post-marketing surveillance data of biologicals in the vulnerable group of JIA patients. Such an international pharmacovigilance database, called Pharmachild, has now been started.

7. Canada pubmed.ncbi.nlm.nih.gov

Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan. [2022] To assess the longterm safety and effectiveness of tocilizumab (TCZ) in systemic-onset juvenile idiopathic arthritis (sJIA).

8. England pubmed.ncbi.nlm.nih.gov

Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan. [2022] To evaluate the safety and effectiveness of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA) in real-world clinical settings in Japan.

9. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study. [2018] Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA.

10. England pubmed.ncbi.nlm.nih.gov

Investigational drugs for treatment of juvenile idiopathic arthritis. [2022] Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The improvement of knowledge about the pathogenetic mechanisms of JIA and advances in the understanding of pathways linking inflammation and autoimmunity and functions of multiple transcription factors have translated into new drug development for a tailored treatment directed to specific subpopulations of JIA patients. Areas covered: This review provides a digest of new investigational drugs which are currently or have been recently tested for treatment of JIA, and highlights some early phase clinical trials on rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab. Expert opinion: Several studies have been focused on multiple complementary pathways driving synovial inflammation in JIA or molecules implicated in the inflammatory signature of JIA to deliver durable effects and prevent long-term complications. Since JIA is a complex disorder with multiple faces, identifying new treatment options for patients nonresponsive to the current drug armamentarium is of great relevance. A number of agents have been developed in the very last years, such as givinostat and tofacitinib, showing promising results in some cases, but trials remain in an early phase and few agents are currently under evaluation in a further phase setting. Longer-term use in possibly high numbers of patients and adequate data collection using large-scale registries are necessary to confirm clinical efficacy and provide a well-balanced overview of safety issues related to the drugs presented in this review.