A Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Golimumab in Patients With Rheumatoid Arthritis (RA)

Study Overview
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Brief Summary
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This is a Phase 1, pharmacokinetic and pharmacodynamic study of intravenous and subcutaneous administered golimumab in patients with rheumatoid arthritis.

Detailed Description
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A Phase 1, randomized (study drug route of administration assigned by chance), open label (both physician and patient know that golimumab has been assigned), study of golimumab in patients with rheumatoid arthritis (RA). The purpose of this study is to compare the pharmacokinetic (how the body effects the drug) and pharmacodynamic (how the drug effects the body) effects of golimumab administered through a vein in the arm or by injection under the skin. Safety assessments will be performed throughout the study and include obtaining and evaluating laboratory tests, vital signs (eg, blood pressure), and the occurrence and severity of adverse events. The study will also assess the clinical effects of golimumab on RA. The study is planned for approximately 45 patients, which are randomized at a 2:1 ratio to receive golimumab SC or IV. Male or female patients who have been diagnosed with RA for at least 3 months and who are 18 years of age or older may be able to participate. Subcutaneous (SC) injections of 100 mg golimumab every 4 weeks through Week 20 or intravenous (IV) administrations of 2 mg/kg golimumab on Days 1 and 85.

Official Title
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An Open-label Randomized Phase 1 Study to Investigate the Pharmacokinetics and Pharmacodynamics of Subcutaneous and Intravenous Administrations of Golimumab to Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Golimumab
* Drug: Golimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of RA for at least 3 months prior to screening Have no history of latent or active tuberculosis (TB) and test negative for TB Exclusion Criteria: Have inflammatory diseases other than RA Have been treated with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives other than methotrexate (MTX), sulfasalazine, or hydroxychloroquine during the 4 weeks prior to the first administration of study agent Have received intramuscular (IM), IV, or intra-articular corticosteroids within 4 weeks of study agent administration Have a known hypersensitivity to human Ig proteins Have received infliximab, golimumab, adalimumab or abatacept within 3 months, or etanercept or anakinra within 1 month prior to the first administration of study agent Have received alefacept, efalizumab, natalizumab, rituximab, or any B-cell-depleting agent Have been treated with any other biologics or investigational drugs, within 5 half-lives of that drug prior to the first administration of study agent Have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis, prior to screening Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening Have had a serious infection (eg, hepatitis, pneumonia, pyelonephritis, or sepsis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Golimumab IV infusions of 2 mg/kg golimumab on Days 1 and 85. | Drug: Golimumab<br>* IV infusions of 2 mg/kg golimumab on Days 1 and 85.<br>|
| Experimental: 002<br>Golimumab SC injection of 100 mg every 4 weeks through Week 20 | Drug: Golimumab<br>* SC injection of 100 mg every 4 weeks through Week 20<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) (Cmax, AUClast, AUCinf, t1/2, systemic clearance, and volume of distribution) following IV administration |  | 169 days | 
| Pharmacokinetics (PK) [Cmax, tmax, AUC (0-4wk), t1/2 for last dose only, R[AUC(0-4wk)] following SC administration |  | 211 days | 
| Plasma concentrations of golimumab following IV administration |  | 169 days | 
| Plasma concentrations of golimumab following SC administration |  | 211 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD), including C-reactive protein, IL 6, serum amyloid A, tumor necrosis factor alpha, IL 18, E selectin, vascular endothelial growth factor, matrix metalloproteinases, leptin, and haptoglobin |  | up to 211 days | 
| ACR (American College of Rheumatology) scores |  | up to 169 days | 
| The number and severity of adverse events |  | up to 211 days | 
| Efficacy as assessed by percent change in the American College of Rheumatology (ACR) score |  | up to 169 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Golimumab, Simponi, Rheumatoid Arthritis, PK, PD