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

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Golimumab; Drug: Golimumab

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 Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States
  • Florida
    • Aventura, Florida, United States
    • Palm Harbor, Florida, United States
  • Kentucky
    • Lexington, Kentucky, United States
  • Louisiana
    • Baton Rouge, Louisiana, United States
  • Massachusetts
    • Worcester, Massachusetts, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
  • Texas
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Centocor, Inc.

Publications and helpful links

General Publications

• Doyle MK, Rahman MU, Frederick B, Birbara CA, de Vries D, Toedter G, Wu X, Chen D, Ranganath VK, Westerman ME, Furst DE. Effects of subcutaneous and intravenous golimumab on inflammatory biomarkers in patients with rheumatoid arthritis: results of a phase 1, randomized, open-label trial. Rheumatology (Oxford). 2013 Jul;52(7):1214-9. doi: 10.1093/rheumatology/kes381. Epub 2013 Feb 14.
• Zhuang Y, Xu Z, Frederick B, de Vries DE, Ford JA, Keen M, Doyle MK, Petty KJ, Davis HM, Zhou H. Golimumab pharmacokinetics after repeated subcutaneous and intravenous administrations in patients with rheumatoid arthritis and the effect of concomitant methotrexate: an open-label, randomized study. Clin Ther. 2012 Jan;34(1):77-90. doi: 10.1016/j.clinthera.2011.11.015. Epub 2011 Dec 14.

Helpful Links

• 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

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 26, 2007
• Primary Completion (ACTUAL): February 27, 2009
• Study Completion (ACTUAL): February 27, 2009

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: May 27, 2011
• First Posted (ESTIMATE): May 30, 2011

Study Record Updates

• Last Update Posted (ACTUAL): October 2, 2017
• Last Update Submitted That Met QC Criteria: September 28, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: PK; Rheumatoid Arthritis; Golimumab; PD; Simponi
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal; Golimumab
• Other Study ID Numbers: CR015550; C0524T14 (OTHER: Centocor)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No