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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn more about how adult and children's bodies use etanercept and how bodyweight influences how well etanercept works. This study will help us understand the proper dose of etanercept in obese children and adults.

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.

What data supports the effectiveness of the drug Etanercept for arthritis?

Research shows that Etanercept, a drug used to treat rheumatoid arthritis, has been effective in improving symptoms when added to methotrexate therapy, especially in patients who did not fully respond to methotrexate alone. It has also shown effectiveness in managing juvenile idiopathic arthritis, with only minor side effects reported. ^{1 2 3 4 5}

Is Etanercept generally safe for humans?

Etanercept has been shown to be generally safe in humans, with minor side effects like injection site reactions and mild infections. In some cases, a rash may develop, but these side effects typically do not require stopping the treatment. ^{1 3 5 6 7}

What makes the drug Etanercept unique for treating arthritis?

Etanercept is unique because it is a fusion protein that blocks tumor necrosis factor (TNF), a substance in the body that causes inflammation, and it is used to treat various forms of arthritis, including rheumatoid arthritis and juvenile idiopathic arthritis. It is administered as an injection and has shown rapid, dose-dependent improvement in symptoms, making it effective for patients who do not respond to other treatments like methotrexate. ^{1 3 5 6 8}

Research Team

Stephen Balevic, MD

Principal Investigator

Duke Clinical Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

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

Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. [2022]

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

Biochemical characterization of a new recombinant TNF receptor-hyFc fusion protein expressed in CHO cells. [2015]

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

Construction and purification of the murine p75-murine IgG1 fusion protein. [2016]

4. United States 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. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Etanercept and urticaria in patients with juvenile idiopathic arthritis. [2017]

6. Switzerland 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and immunogenicity of T0001, a newly developed anti-TNFα fusion protein, in healthy volunteers. [2018]

8. France pubmed.ncbi.nlm.nih.gov

Collaborative study for the establishment of Etanercept Biological Reference Preparation Batch 1. [2021]