Upadacitinib + Tocilizumab for Juvenile Idiopathic Arthritis

(SELECT-sJIA Trial)

Recruiting at 46 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

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. ^{1 2 3 4 5}

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. ^{1 2 6 7 8}

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. ^{1 2 3 9 10}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

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.

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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]

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]

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]

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]

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

Tocilizumab for the treatment of juvenile idiopathic arthritis. [2016]

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]

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]

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]

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

What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis? [2022]

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]

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]

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]

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

Investigational drugs for treatment of juvenile idiopathic arthritis. [2022]