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

Sponsor

Centocor, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01362153

Collaborator

(none)

Enrollment

Locations

Arms

14.1

Actual Duration (Months)

5.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Golimumab Drug: Golimumab	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 26, 2007

Actual Primary Completion Date :

Feb 27, 2009

Actual Study Completion Date :

Feb 27, 2009

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 001

Golimumab IV infusions of 2 mg/kg golimumab on Days 1 and 85.

Drug: Golimumab

IV infusions of 2 mg/kg golimumab on Days 1 and 85.

Experimental: 002

Golimumab SC injection of 100 mg every 4 weeks through Week 20

Drug: Golimumab

SC injection of 100 mg every 4 weeks through Week 20

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	City	State	Country
1	Glendale	Arizona	United States
2	Aventura	Florida	United States
3	Palm Harbor	Florida	United States
4	Lexington	Kentucky	United States
5	Baton Rouge	Louisiana	United States
6	Worcester	Massachusetts	United States
7	Oklahoma City	Oklahoma	United States
8	Duncansville	Pennsylvania	United States
9	Houston	Texas	United States