Sarilumab for Juvenile Idiopathic Arthritis

Recruiting at 87 trial locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sanofi

Must not be taking: Anti-IL-6, Biologics, JAK inhibitors, others

Disqualifiers: Severe systemic symptoms, Lung disease, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing sarilumab, a medication that reduces inflammation, in children and teenagers with a specific type of arthritis called sJIA. The medication works by blocking a protein that causes inflammation.

Will I have to stop taking my current medications?

The trial requires that certain medications be stable for a period before starting, like NSAIDs for 2 weeks and non-biologic DMARDs for 6 weeks. Some treatments, like biologics for sJIA, must be stopped for a specific time before the trial. Check with the trial team for details on your specific medications.

What data supports the effectiveness of the drug Sarilumab (Kevzara) for treating Juvenile Idiopathic Arthritis?

While there is no direct data on Sarilumab for Juvenile Idiopathic Arthritis, similar drugs like tocilizumab, which also targets inflammation, have shown effectiveness in treating polyarticular-course juvenile idiopathic arthritis, suggesting potential benefits of Sarilumab for similar conditions. ^{1 2 3 4 5}

Is Sarilumab safe for use in humans?

Sarilumab, also known as Kevzara, has been approved for treating rheumatoid arthritis in adults and is being studied for juvenile idiopathic arthritis. It has been shown to be generally safe, but like other similar treatments, it may cause side effects such as serious infections. Ongoing monitoring and data collection are important to ensure its safety in children. ^{6 7 8 9 10}

How is the drug Sarilumab different from other treatments for juvenile idiopathic arthritis?

Sarilumab is unique because it targets the interleukin-6 receptor, which is a different mechanism compared to other treatments like adalimumab that target tumor necrosis factor. This different approach may offer an alternative for patients who do not respond well to other treatments. ^{11 12 13 14 15}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for children and adolescents aged 1-17 with Systemic Juvenile Idiopathic Arthritis (sJIA) who haven't responded well to current treatments. They should not have used certain arthritis drugs recently, can't be on high doses of steroids, or have had live vaccines in the last month. Participants must weigh between 10 kg and 60 kg for initial dose groups.

Inclusion Criteria

I have been diagnosed with systemic juvenile idiopathic arthritis.

I have systemic JIA with fever and 2 active joints despite stable glucocorticoid treatment.

My current arthritis treatment isn't working, and my doctor thinks I need a stronger medication.

Exclusion Criteria

I have not received any live vaccines in the last 4 weeks.

I have severe heart problems because of my systemic juvenile idiopathic arthritis.

I have a history of lung problems like interstitial lung disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Core Treatment

Participants receive sarilumab by subcutaneous injection during the core treatment phase

12 weeks

Extension Treatment

Participants continue to receive sarilumab during the extension phase

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• Sarilumab (Monoclonal Antibodies)

Trial Overview The study tests Sarilumab's effects, dosage, and safety in young patients with sJIA. It aims to find the right dose for effective treatment by observing how the drug behaves in their bodies (pharmacokinetics) and its impact on the disease (pharmacodynamics).

Participant Groups

Group I: Sarilumab Experimental Treatment 1 Intervention

Participants will receive one of two ascending doses (or an additional intermediate dose based on available data) of sarilumab by subcutaneous (SC) injection based on body weight. All the participants will receive the selected dose once the selected dose is identified. Sarilumab will be given during 12-week core treatment phase followed by a 144- week extension treatment phase.

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

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]

In a 2-year pilot study involving 24 young adults with refractory juvenile idiopathic arthritis (JIA), the combination of infliximab and methotrexate (MTX) led to significant improvements in joint activity and pain levels, with many patients showing a 20% improvement in their condition.

The treatment was generally safe, with 50% of patients experiencing adverse events, but it demonstrated high effectiveness in reducing disease activity and improving overall health, indicating potential for further research in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. Gerloni, V., Pontikaki, I., Gattinara, M., et al.[2015]

Juvenile idiopathic arthritis treatment has significantly improved over the past 20 years due to new medications and collaborative efforts, but many patients still do not respond to current therapies.

Future advancements in treatment will rely on better defining the disease types, identifying biomarkers for personalized therapy, and developing new drugs that specifically target inflammatory pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future perspectives in the management of juvenile idiopathic arthritis. Ruperto, N., Martini, A.[2019]

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]

Despite the availability of many biological and targeted treatments for Juvenile Idiopathic Arthritis (JIA), over 50% of affected children and young people continue to experience significant disease activity and require ongoing immune suppression into adulthood.

Current treatment strategies for JIA rely on a trial-and-error approach due to the lack of validated tools and biomarkers for selecting specific therapies, highlighting the need for a molecular-based approach to improve treatment precision and clinical trial design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis. Wedderburn, LR., Ramanan, AV., Croft, AP., et al.[2023]

Sarilumab is a fully human monoclonal antibody that effectively inhibits IL-6 signaling by binding to both soluble and membrane-bound IL-6 receptors, making it a targeted treatment for rheumatoid arthritis.

Approved in Canada for adults with moderate to severe rheumatoid arthritis who did not respond adequately to other treatments, sarilumab is also being investigated for juvenile idiopathic arthritis and is under review in multiple countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarilumab: First Global Approval. Scott, LJ.[2018]

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]

Adalimumab demonstrated long-term safety and efficacy in treating juvenile idiopathic arthritis (JIA) over 6 years, with significant clinical responses observed in 66% to 96% of patients achieving various levels of improvement by week 104.

The treatment was well tolerated, with only 12 serious infections reported among 171 patients over 592.8 patient-years, and no severe adverse events like heart failure or malignancies, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate. Lovell, DJ., Brunner, HI., Reiff, AO., et al.[2021]

In a study involving 536 rheumatoid arthritis patients, sarilumab was found to be effective in reducing disease activity in those who had previously not responded to Janus kinase inhibitors (JAKi) and tocilizumab, with consistent safety results over a 6-month treatment period.

The safety profile of sarilumab remained as expected, with no new safety concerns identified, and the rates of patients discontinuing the study were similar across different treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sarilumab reduces disease activity in rheumatoid arthritis patients with inadequate response to janus kinase inhibitors or tocilizumab in regular care in Germany. Tony, HP., Feist, E., Aries, PM., et al.[2022]

In a study involving patients with rheumatoid arthritis, both sarilumab and tocilizumab showed similar safety profiles, with no significant differences in treatment-emergent adverse events, indicating that both medications can be considered safe options.

Common adverse events included neutropenia and infections, but there was no link between decreased neutrophil counts and increased infection rates, suggesting that these treatments can be tolerated well by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis. Emery, P., Rondon, J., Parrino, J., et al.[2020]

In a study of 39 patients with juvenile idiopathic arthritis (JIA) and refractory uveitis, adalimumab significantly reduced inflammation in both the anterior and posterior segments of the eye after 6 months of treatment, indicating its efficacy.

The treatment also led to a significant decrease in the need for corticosteroids, suggesting that adalimumab may help manage symptoms while reducing reliance on more potent immunosuppressive therapies, with no major side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. García-De-Vicuña, C., Díaz-Llopis, M., Salom, D., et al.[2022]

Adalimumab is highly effective in treating juvenile idiopathic arthritis (JIA), with significant improvements in disease activity observed in both biologics-naive patients and those switching from other biologic treatments, as indicated by the American College of Rheumatology Pediatric response criteria.

The treatment is considered safe, with a low incidence of serious adverse events (2.5 per 100 patient-years) and no reported malignancies, suggesting that adalimumab is a viable option for managing JIA in children and adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adalimumab as the first and second biologic agent in juvenile idiopathic arthritis: the German Biologics JIA Registry. Schmeling, H., Minden, K., Foeldvari, I., et al.[2016]

In a study of 11 juvenile idiopathic arthritis (JIA) patients with uveitis, adalimumab was effective as a first-line treatment, with 63.64% achieving complete remission after two years.

No relapses of uveitis were observed during the treatment, and patients were able to taper off topical steroids, indicating both safety and efficacy of adalimumab in managing JIA with associated uveitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes. Lazarević, D., Nikolić, I., Ratković-Janković, M., et al.[2022]

Adalimumab significantly improved inflammation in patients with early onset, chronic anterior uveitis associated with juvenile idiopathic arthritis, showing a 30% reduction in inflammation at month 2 compared to placebo (9 out of 16 responders vs. 3 out of 15, P=0.038).

The treatment was generally safe, with no serious adverse events linked to adalimumab, suggesting it is a viable option for patients who do not respond adequately to topical steroids and methotrexate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Quartier, P., Baptiste, A., Despert, V., et al.[2019]

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]

References

1. 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]

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

Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistently active, refractory juvenile idiopathic arthritis: results of an open-label prospective study. [2015]

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

Current and future perspectives in the management of juvenile idiopathic arthritis. [2019]

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. England pubmed.ncbi.nlm.nih.gov

Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Sarilumab: First Global Approval. [2018]

7. England pubmed.ncbi.nlm.nih.gov

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

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

Long-term outcomes in patients with polyarticular juvenile idiopathic arthritis receiving adalimumab with or without methotrexate. [2021]

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

Sarilumab reduces disease activity in rheumatoid arthritis patients with inadequate response to janus kinase inhibitors or tocilizumab in regular care in Germany. [2022]

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

Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis. [2020]

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

Usefulness of adalimumab in the treatment of refractory uveitis associated with juvenile idiopathic arthritis. [2022]

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

Efficacy and safety of adalimumab as the first and second biologic agent in juvenile idiopathic arthritis: the German Biologics JIA Registry. [2016]

13. Turkey pubmed.ncbi.nlm.nih.gov

Outcome of Juvenile Idiopathic Arthritis Associated Uveitis in Two Disease Subtypes. [2022]

14. England pubmed.ncbi.nlm.nih.gov

ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. [2019]

15. 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]