Upadacitinib + Tocilizumab for Juvenile Idiopathic Arthritis

(SELECT-sJIA Trial)

Recruiting at 65 trial locations

Overseen By ABBVIE CALL CENTER

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: IL-6 inhibitors

Disqualifiers: Other JIA, Autoimmune conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of the investigational drug upadacitinib for treating systemic juvenile idiopathic arthritis (sJIA), a severe form of arthritis in children that can affect the entire body. Participants will be divided into two groups: one will receive upadacitinib, and the other will receive either upadacitinib or tocilizumab (a known treatment for sJIA) for comparison. The trial aims to determine if upadacitinib can reduce symptoms such as joint swelling and fever. This trial may suit those who have experienced sJIA symptoms for at least six weeks, with at least two joints affected and a poor response to traditional treatments. Participants will take medication for 52 weeks and attend regular check-ups to monitor progress. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that upadacitinib is generally safe for children with juvenile idiopathic arthritis. Studies found that adjusting the dose based on body weight works well and is safe for kids. Common side effects include headache, nausea, and colds, but these are usually mild.

Tocilizumab is also considered safe for children with systemic juvenile idiopathic arthritis (sJIA). Research indicates it helps manage the disease over time. While it might increase the chance of serious infections, many children handle it well. Monitoring for side effects is important, but both treatments have demonstrated promising safety in past studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Upadacitinib is unique because it targets Janus kinase (JAK) pathways, which play a crucial role in the inflammatory process of juvenile idiopathic arthritis. Unlike traditional treatments like methotrexate or biologics such as TNF inhibitors, which broadly suppress the immune system, upadacitinib offers a more targeted approach that can potentially reduce inflammation with fewer side effects. Tocilizumab, on the other hand, is already an established treatment, working by blocking the interleukin-6 (IL-6) receptor, but researchers are excited to compare its efficacy directly with upadacitinib. This comparison could reveal insights into more personalized treatment plans for young patients.

What evidence suggests that this trial's treatments could be effective for systemic juvenile idiopathic arthritis?

Research has shown that upadacitinib, which participants in this trial may receive, holds promise for treating juvenile idiopathic arthritis (JIA). In an earlier study, 61.2% of patients experienced significant symptom improvement as early as the first week of treatment, with further progress by week 24. Upadacitinib has also proven effective in children with other types of arthritis, similar to its effects in adults. Meanwhile, tocilizumab, another treatment option in this trial, is already a well-known treatment for JIA, relieving symptoms by reducing inflammation. This trial tests both treatments to evaluate their effectiveness for systemic JIA, a more severe form of the disease. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tocilizumab
• Upadacitinib

Trial Overview 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.

How Is the Trial Designed?

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 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

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

The review highlights the immunological side effects of various biological therapies used in juvenile idiopathic arthritis (JIA), detailing the incidence of serious infections, tuberculosis, malignancies, and other adverse events per 100 patient-years.

There is a significant variation in side effects among different biological agents, underscoring the need for a standardized international database, Pharmachild, to monitor and collect post-marketing safety data for these treatments in JIA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis? Swart, JF., de Roock, S., Wulffraat, NM.[2022]

Tocilizumab (TCZ) has shown long-term effectiveness in treating systemic-onset juvenile idiopathic arthritis (sJIA), with sustained American College of Rheumatology (ACR) response rates maintained over a median exposure of 3.4 years in 67 patients.

The treatment demonstrated good safety, with a low rate of serious adverse events (34.7 per 100 patient-years) and no reported cases of malignancy or death, indicating that TCZ is a tolerable option for long-term management of sJIA.

NCBI (Pubmed)

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. Yokota, S., Imagawa, T., Mori, M., et al.[2022]

In a real-world study of 417 pediatric patients with systemic juvenile idiopathic arthritis (sJIA) treated with tocilizumab (TCZ) over 52 weeks, the medication was found to be well tolerated, showing acceptable safety and effectiveness.

While TCZ led to significant improvements in symptoms and normal C-reactive protein levels, the study reported higher rates of serious adverse events (SAEs) and serious infections compared to previous clinical trials, likely due to differences in patient characteristics such as higher corticosteroid use.

NCBI (Pubmed)

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. Yokota, S., Itoh, Y., Morio, T., et al.[2022]

Tofacitinib was found to be well tolerated in children with juvenile idiopathic arthritis (JIA), with no serious adverse events reported during the study involving 26 participants aged 2 to 17 years.

The study established effective dosing regimens for tofacitinib based on age and body weight, and confirmed that the oral solution had an acceptable taste, making it suitable for pediatric use.

NCBI (Pubmed)

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. Ruperto, N., Brunner, HI., Zuber, Z., et al.[2018]

In a phase III trial involving 187 patients with polyarticular-course juvenile idiopathic arthritis (pcJIA), treatment with tocilizumab (TCZ) for up to 2 years resulted in a significant increase in height standard deviation score (SDS) by +0.40, indicating improved growth in these patients.

Among those patients who were at Tanner stage ≤ 3 at baseline, 72% experienced an increase in height SDS, with a mean height velocity of 6.7 cm/year, demonstrating the efficacy of TCZ in promoting growth in children with pcJIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth During Tocilizumab Therapy for Polyarticular-course Juvenile Idiopathic Arthritis: 2-year Data from a Phase III Clinical Trial. Bharucha, KN., Brunner, HI., Calvo Penadés, I., et al.[2019]

Tocilizumab is FDA-approved for treating systemic juvenile idiopathic arthritis in patients aged 2 years and older and has shown superior efficacy compared to placebo in Phase 2 and 3 clinical trials.

The treatment is considered safe, with only a few serious adverse events reported, and has demonstrated effectiveness for up to 52 weeks, making it a valuable option for patients who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of juvenile idiopathic arthritis. Decelle, K., Horton, ER.[2016]

In a study involving 188 patients with polyarticular-course juvenile idiopathic arthritis (pcJIA), tocilizumab significantly reduced the risk of disease flare compared to placebo, with 25.6% of patients on tocilizumab experiencing a flare versus 48.1% on placebo (p=0.0024).

Tocilizumab demonstrated substantial efficacy, with 64.6% of patients achieving a JIA-ACR70 response and 45.1% achieving a JIA-ACR90 response, while maintaining a safety profile similar to that observed in adults with rheumatoid arthritis, with infections being the most common serious adverse event.

NCBI (Pubmed)

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. Brunner, HI., Ruperto, N., Zuber, Z., et al.[2022]

In a study of 188 patients aged 2-17 with polyarticular-course juvenile idiopathic arthritis (JIA), tocilizumab (TCZ) demonstrated high efficacy over 2 years, with JIA-ACR50/70/90 response rates of 80.3%, 77.1%, and 59.6% respectively, and over half of the patients achieving inactive disease by week 104.

The safety profile of TCZ was consistent with previous reports, with adverse event rates of 406.5 per 100 patient-years and serious infections at 5.2 per 100 patient-years, indicating that TCZ is a relatively safe option for long-term treatment of JIA.

NCBI (Pubmed)

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. Brunner, HI., Ruperto, N., Zuber, Z., et al.[2021]

Recent advancements in understanding juvenile idiopathic arthritis (JIA) have led to the development of new investigational drugs, such as rilonacept, givinostat, daclizumab, tofacitinib, and sarilumab, aimed at targeting specific pathways involved in the disease.

Early-phase clinical trials for drugs like givinostat and tofacitinib show promising results, but further research with larger patient groups and long-term data collection is essential to confirm their efficacy and safety for treating JIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational drugs for treatment of juvenile idiopathic arthritis. Mauro, A., Rigante, D., Cimaz, R.[2022]

In a study of 56 children with systemic-onset juvenile idiopathic arthritis, tocilizumab showed high efficacy, with 91% of patients achieving a significant response (ACR Pedi 30) after an initial treatment phase.

In the double-blind phase, 80% of patients receiving tocilizumab maintained their response compared to only 17% in the placebo group, highlighting its effectiveness as a treatment option for this challenging condition.

NCBI (Pubmed)

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. Yokota, S., Imagawa, T., Mori, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12038220/

Pharmacokinetics, Efficacy, and Safety of Upadacitinib in ... Response to upadacitinib was rapid, with 61.2% of patients achieving JIA ACR 30 as early as week 1. JIA ACR responses continued to improve at week 24 and were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05609630

NCT05609630 | Study of Oral Upadacitinib and ... This study will assess how safe and effective upadacitinib is in treating pediatric and adolescent participants aged 1 to < 18 with systemic juvenile idiopathic ...

3. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/full/10.1002/cpt.3441

Extrapolation of Upadacitinib Efficacy in Juvenile Idiopathic ... Simulations demonstrate that upadacitinib efficacy in pcJIA and JPsA is predicted to be non-inferior to that in adults with RA or PsA, respectively.

4. rinvoqhcp.com rinvoqhcp.com/rheumatoid-arthritis/efficacy

RINVOQ® (upadacitinib) Efficacy for Rheumatoid Arthritis View clinical trial overview and efficacy data that studied the effects of RINVOQ on moderate to severe Rheumatoid Arthritis.

5. news.abbvie.com news.abbvie.com/2024-06-04-RINVOQ-R-upadacitinib-Now-Available-for-Pediatric-Patients-Two-Years-and-Older-with-Polyarticular-Juvenile-Idiopathic-Arthritis-and-Psoriatic-Arthritis

RINVOQ® (upadacitinib) Now Available for Pediatric ... It is not known if RINVOQ/RINVOQ LQ is safe and effective in children under 2 years of age with polyarticular juvenile idiopathic arthritis or ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3512171/

Efficacy, safety and tolerability of tocilizumab in patients with ... Several phase II and III clinical trials of a humanized anti-IL-6 receptor antibody, tocilizumab, proved its outstanding efficacy and tolerable safety profile ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00642460

A Study of RoActemra/Actemra (Tocilizumab) in Patients ... This study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active systemic juvenile idiopathic arthritis (sJIA) ...

8. academic.oup.com academic.oup.com/rheumatology/article/63/9/2535/7637686

Long-term efficacy and safety of subcutaneous tocilizumab in ... Patients with polyarticular/systemic juvenile idiopathic arthritis experienced long-term disease control with subcutaneous tocilizumab.

9. actemrahcp.com actemrahcp.com/sjia/safety-profile.html

SJIA Safety Profile & Adverse Events - ACTEMRA® (tocilizumab) Patients treated with ACTEMRA are at increased risk for developing serious infections that may lead to hospitalization or death.

10. ard.bmj.com ard.bmj.com/content/74/6/1110

Efficacy and safety of tocilizumab in patients with polyarticular ... Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with ...