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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Golimumab

• Registration Number: NCT01362153
• Lead Sponsor: Centocor, Inc.

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2007-12-26
• Primary Completion: 2009-02-27
• Study Completion: 2009-02-27
• Study First Submitted: 2011-03-10
• Study First Submitted QC: 2011-05-27
• Study First Posted: 2011-05-30
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-28
• Last Update Posted: 2017-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
001	Golimumab	Golimumab IV infusions of 2 mg/kg golimumab on Days 1 and 85.
002	Golimumab	Golimumab SC injection of 100 mg every 4 weeks through Week 20

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) (Cmax, AUClast, AUCinf, t1/2, systemic clearance, and volume of distribution) following IV administration	169 days
Plasma concentrations of golimumab following SC administration	211 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

Secondary Outcome Measures

Name	Time	Method
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
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
ACR (American College of Rheumatology) scores	up to 169 days