Etanercept Dosing for Arthritis

(PRECISE Trial)

Overseen By Balevic Stephen, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Duke University

Must be taking: Etanercept

Must not be taking: Biologics

Disqualifiers: Malignancy, Heart failure, Severe infections, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the medication etanercept (a TNF receptor fusion protein) works in adults and children with arthritis, focusing on the impact of body weight on its effectiveness. The researchers aim to find the best dose for obese individuals with juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA). They seek participants who are beginning etanercept as part of their regular treatment plan, are obese, and have active arthritis symptoms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking arthritis research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that if you are using oral corticosteroids or DMARDs, you must be on a stable dose for at least 4 weeks before starting the trial.

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

Research has shown that etanercept is generally safe for people with juvenile idiopathic arthritis (JIA). Studies found no new safety issues and no increased risk of cancer or other autoimmune disorders. However, there is a known risk of serious infections that can lead to hospitalization. These infections are a serious concern but do not affect everyone. Overall, many patients tolerate etanercept well, but awareness of these potential risks is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Etanercept is unique because it offers a targeted approach to treating juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA). Unlike traditional treatments that may broadly suppress the immune system, etanercept specifically blocks tumor necrosis factor (TNF), a substance in the body that leads to inflammation and joint damage in these conditions. Researchers are particularly excited about its potential to optimize dosing for obese children and adults, which could enhance effectiveness and minimize side effects, making treatment more personalized and precise.

What evidence suggests that etanercept might be an effective treatment for arthritis?

Research has shown that etanercept effectively treats juvenile idiopathic arthritis (JIA). One study found that 74% of patients experienced noticeable improvement after three months of treatment. The drug has been tested at various doses and consistently helps manage symptoms. Long-term evidence supports its use, with many patients maintaining good health even after five years. This indicates the treatment's effectiveness for many who continue using it. Overall, etanercept has a strong track record of helping patients with JIA and similar conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Stephen Balevic, MD

Principal Investigator

Duke Clinical Research Institute

Are You a Good Fit for This Trial?

This trial is for obese adults and children with active arthritis, specifically Rheumatoid Arthritis or Juvenile Idiopathic Arthritis. Participants must be starting etanercept treatment and have not used biologics recently. They can't join if they're pregnant, planning pregnancy, allergic to etanercept, have certain infections or severe blood, liver or kidney issues.

Inclusion Criteria

My disease activity score is high, indicating active disease.

I have been on a stable dose of oral corticosteroids or DMARDs for at least 4 weeks.

I have been diagnosed with Juvenile Idiopathic Arthritis and I am under 16.

Exclusion Criteria

Positive urine pregnancy test at screening or planned pregnancy during the study period

I haven't taken etanercept or similar drugs recently.

Contraindication to etanercept (e.g., allergy, current or chronic infection [positive tuberculosis screening test, positive hepatitis B surface antigen, positive hepatitis C antibody])

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etanercept as part of their routine medical care, with PK and PD assessments

6 weeks

5 blood samples collected through clinic and home visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etanercept

Trial Overview The study aims to determine the optimal dosing of a drug called Etanercept in obese patients with arthritis. It will assess how different body weights affect the drug's effectiveness and metabolism in both adult and pediatric patients.

How Is the Trial Designed?

Group I: Optimal dosing Experimental Treatment 1 Intervention

Obese children (≥ 2 year old) and adults with juvenile idiopathic arthritis (JIA) or Rheumatoid Arthritis (RA) who are starting etanercept as part of their routine medical care.

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

Approved in United States as Enbrel for:

• Moderate to Severe Rheumatoid Arthritis
• Moderate to Severe Polyarticular Juvenile Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Moderate to Severe Plaque Psoriasis

Approved in European Union as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Approved in Canada as Enbrel for:

• Rheumatoid Arthritis
• Juvenile Idiopathic Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
• Plaque Psoriasis

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

Etanercept has shown preliminary effectiveness in treating methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA), suggesting it could be a valuable option for patients who do not respond to standard treatments.

While most side effects of etanercept have been minor, two patients experienced a urticaria-like rash after injections, indicating that while generally safe, some individuals may have specific adverse reactions that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. Skyttä, E., Pohjankoski, H., Savolainen, A.[2017]

T0001, a new recombinant fusion protein, was found to be safe and well-tolerated in a first-in-human trial involving 56 healthy Chinese volunteers, with no serious adverse events reported.

The pharmacokinetics of T0001 showed a slow absorption and elimination rate, with increasing plasma concentrations of TNFα after administration, although the study could not confirm linear pharmacokinetics across the tested doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and immunogenicity of T0001, a newly developed anti-TNFα fusion protein, in healthy volunteers. Wang, Y., Liu, C., Chen, S., et al.[2018]

A novel hybrid protein, TNFR-hyFc, was developed to reduce unwanted immune responses like antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are concerns with existing TNF-α blockers like etanercept.

Pre-clinical evaluations showed that TNFR-hyFc has a similar biochemical profile to etanercept but is slightly larger and more acidic, suggesting it may offer a safer alternative with reduced side effects in treating conditions related to TNF-α.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical characterization of a new recombinant TNF receptor-hyFc fusion protein expressed in CHO cells. Lee, JH., Yeo, J., Park, HS., et al.[2015]

In a randomized, double-blind, placebo-controlled trial involving 234 patients with active rheumatoid arthritis, etanercept demonstrated significant improvements in disease activity over 6 months, with 59% of patients achieving a 20% improvement compared to only 11% in the placebo group.

Etanercept was well tolerated and showed a dose-dependent effect, with no dose-limiting toxic effects, confirming its safety and efficacy as a treatment for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Moreland, LW., Schiff, MH., Baumgartner, SW., et al.[2022]

Etanercept is a fusion protein that acts as a soluble receptor for tumor necrosis factor (TNF), effectively used to treat various chronic inflammatory diseases in humans, such as rheumatoid arthritis and psoriasis.

To study its effects in mouse models, researchers developed a murine version of the soluble p75-TNF receptor, allowing for better understanding of its mechanism in conditions that mimic human granulomatous infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction and purification of the murine p75-murine IgG1 fusion protein. Kim, HY., Renshaw-Gegg, LW., Balciunas, AM., et al.[2016]

In a 24-week study involving 60 children with juvenile idiopathic arthritis (JIA), treatment with the etanercept biosimilar rhTNFR-Fc combined with methotrexate led to a significant reduction in disease activity, as measured by the cJADAS-10 score, which dropped from 14.66 to 2.4 (P < 0.01).

Approximately half of the patients achieved inactive disease status after 24 weeks, and improvements were also observed in symptoms like morning stiffness and joint effusions, indicating that rhTNFR-Fc is both effective and safe for treating JIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of etanercept biosimilar rhTNFR-Fc in Chinese patients with juvenile idiopathic arthritis: An open-label multicenter observational study. Xu, X., Liu, X., Zheng, W., et al.[2022]

In a 24-week study involving 89 patients with rheumatoid arthritis who were not responding adequately to methotrexate alone, the addition of etanercept significantly improved clinical outcomes, with 71% of patients achieving a 20% improvement in disease activity compared to only 27% in the placebo group.

The combination therapy was safe and well tolerated, with only mild injection-site reactions reported, indicating that etanercept can be a beneficial addition to methotrexate for patients with persistent disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. Weinblatt, ME., Kremer, JM., Bankhurst, AD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1954640/

Effectiveness of a once weekly double dose of etanercept ... Etanercept is effective in juvenile idiopathic arthritis (JIA).,, Currently it is administered subcutaneously at a dose of 0.4 mg/kg (maximum of 25 mg) ...

2. ped-rheum.biomedcentral.com ped-rheum.biomedcentral.com/articles/10.1186/s12969-024-00989-x

Increasing the etanercept dose in a treat-to-target approach in ... Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12297008/

Update on Biologic Therapy in Juvenile Idiopathic Arthritis Data from national registries in Canada showed that biologic prescription increased from 6% in 2005–2010 to 26% in 2017–2021. This trend was ...

4. jrd.or.kr jrd.or.kr/journal/view.html?uid=1396&vmd=Full

Long Term Safety and Efficacy of Etanercept in Juvenile ... The drug survival rates after 5 years were 73% in the systemic onset JIA group, 89% in the extended oligoarticular group, 93% in the RF-negative ...

5. enbrelpro.com enbrelpro.com/efficacy/juvenile-idiopathic-arthritis

Juvenile Idiopathic Arthritis (JIA) Efficacy | Enbrel® (etanercept) 74% of the patients on ENBREL demonstrated a clinical response (JIA 30) at 3 months. ... JIA 30 at 3 months of the single-arm, open-label period.

6. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-020-02326-5

Long-term safety and effectiveness of etanercept in JIA No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9746218/

Outcome of adult patients with JIA treated with the ... To analyze therapy adherence, safety, and outcome in adult patients with juvenile idiopathic arthritis (JIA) treated with the etanercept biosimilar Benepali.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39088092/

Real-life data of etanercept efficacy and safety in juvenile ... Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for ...

9. enbrelpro.com enbrelpro.com/safety/juvenile-idiopathic-arthritis

Juvenile Idiopathic Arthritis (JIA) Safety | Enbrel® (etanercept) Patients treated with ENBREL are at increased risk for developing serious infections that may lead to hospitalization or death.

10. sciencedirect.com sciencedirect.com/science/article/pii/S0003496724149175

Efficacy and safety of open-label etanercept on extended ... To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis ...