Sarilumab for Juvenile Idiopathic Arthritis

(SKYPS Trial)

Recruiting at 90 trial locations

Overseen By For site information, send an email with site number to

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

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

Disqualifiers: Severe systemic symptoms, Lung disease, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests sarilumab (also known as Kevzara), a medication for children and teens with Systemic Juvenile Idiopathic Arthritis (sJIA), a type of arthritis that causes joint pain and swelling. The main goal is to determine the optimal dose of sarilumab for these young patients. Researchers will also evaluate the drug's long-term effectiveness and safety. Children and teens who haven't found success with their current treatments might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new treatment.

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.

Is there any evidence suggesting that sarilumab is likely to be safe for humans?

Research has shown that sarilumab, also known as Kevzara, has been tested for safety in various conditions, including juvenile idiopathic arthritis (JIA). In past studies, it generally demonstrated a good safety record. For example, in children with polyarticular juvenile idiopathic arthritis (pJIA), common side effects were usually mild, such as a runny nose, low white blood cell counts, and upper respiratory infections.

However, sarilumab carries some risks. It can increase the chance of serious infections, which might require hospital treatment or could even be life-threatening. These infections can result from bacteria, viruses, or fungi. Despite these risks, with careful monitoring, sarilumab has been considered safe enough for treating similar conditions in children.

Overall, while potential risks exist, past studies suggest that with proper medical supervision, sarilumab may be a well-tolerated option for treating Systemic Juvenile Idiopathic Arthritis in young patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Juvenile Idiopathic Arthritis, which often include methotrexate or biologics like TNF inhibitors, Sarilumab is unique because it targets and blocks the interleukin-6 (IL-6) receptor. This mechanism is different from most conventional therapies that focus on tumor necrosis factor (TNF) pathways. Additionally, Sarilumab is administered via subcutaneous injection, which may offer a convenient dosing option for patients compared to intravenous infusions. Researchers are excited because targeting the IL-6 pathway might provide more effective control of inflammation and symptoms for some patients who do not respond well to existing treatments.

What evidence suggests that sarilumab might be an effective treatment for Systemic Juvenile Idiopathic Arthritis?

Research shows that sarilumab effectively treats certain types of arthritis. Studies have confirmed its safety and effectiveness in adults with rheumatoid arthritis. The FDA has approved sarilumab, also known as Kevzara, for treating active polyarticular juvenile idiopathic arthritis, a childhood arthritis affecting multiple joints. This treatment blocks a protein that causes inflammation, helping to reduce pain and swelling. Early research suggests it might also alleviate symptoms of systemic juvenile idiopathic arthritis, but more studies are needed for confirmation. Participants in this trial will receive one of two ascending doses, or an additional intermediate dose based on available data, of sarilumab by subcutaneous injection according to body weight. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Sarilumab

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).

How Is the Trial Designed?

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.

Sarilumab is already approved in European Union, United States for the following indications:

Approved in European Union as Kevzara for:

• Rheumatoid arthritis

Approved in United States as Kevzara for:

• Rheumatoid arthritis
• Polymyalgia rheumatica

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

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02991469

Study Details | NCT02991469 | A Repeated Dose-finding ... To describe the pharmacodynamics (PD) profile, the efficacy, and the long term safety of sarilumab in patients with sJIA. Detailed Description. The total study ...

2. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/kevzarar-sarilumab-approved-fda-treatment-active-polyarticular

Kevzara® (sarilumab) Approved by FDA for the Treatment ... Overall, patients treated with Kevzara are at increased risk for developing serious infections that may lead to hospitalization or death. “This ...

3. kevzara.com kevzara.com/hcp/ra/combination-therapy/efficacy-data

KEVZARA® Combination Therapy Efficacy Data For Polyarticular Juvenile Idiopathic Arthritis: In Study 4, the rate of infections was 146.6 events per 100 patient-years. The most common infections ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6732515/

Clinical evaluation of the safety, efficacy and tolerability ... Three pivotal clinical trials have established sarilumab as one of the safe and efficacious choices for the treatment of RA (mobility, target and monarch ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02776735

Study Details | NCT02776735 | An Open-label, Ascending, ... Primary Objective: To describe the pharmacokinetic (PK) profile of sarilumab in participants aged 2-17 years with Polyarticular-course Juvenile Idiopathic ...

6. kevzara.com kevzara.com/hcp/pmr/safety

KEVZARA® Safety Profile Patients treated with KEVZARA are at increased risk for developing serious infections that may lead to hospitalization or death.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761037s015lbl.pdf

Highlights of prescribing information - accessdata.fda.gov Serious infections leading to hospitalization or death including bacterial, viral, invasive fungal, and other opportunistic infections.

8. kevzara.com kevzara.com/hcp/ra/safety-profile/monotherapy

Monotherapy Safety Profile for KEVZARA Overall, KEVZARA monotherapy long-term safety was studied in 471 patients, with more than 1700 patient-years of exposure, and data were consistent with MONARCH ...

9. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/kevzara

Kevzara | European Medicines Agency (EMA) ... juvenile idiopathic arthritis, Kevzara appears to improve disease symptoms in these children. The safety profile of Kevzara was considered acceptable and in ...

10. empr.com empr.com/home/news/kevzara-approved-for-active-polyarticular-juvenile-idiopathic-arthritis/

Kevzara Approved for Active Polyarticular Juvenile ... The most common adverse reactions reported with sarilumab in patients with pJIA were nasopharyngitis, neutropenia, upper respiratory tract ...