Clinical trial NCT01362153: A Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Golimumab in Patients With Rheumatoid Arthritis (RA)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Golimumab
Simponi
Rheumatoid Arthritis
PK
PD
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-30
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Pharmacokinetics (PK) (Cmax, AUClast, AUCinf, t1/2, systemic clearance, and volume of distribution) following IV administration
timeFrame: 169 days
measure: Pharmacokinetics (PK) [Cmax, tmax, AUC (0-4wk), t1/2 for last dose only, R[AUC(0-4wk)] following SC administration
timeFrame: 211 days
measure: Plasma concentrations of golimumab following IV administration
timeFrame: 169 days
measure: Plasma concentrations of golimumab following SC administration
timeFrame: 211 days
Secondary outcomes:
measure: 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
timeFrame: up to 211 days
measure: ACR (American College of Rheumatology) scores
timeFrame: up to 169 days
measure: The number and severity of adverse events
timeFrame: up to 211 days
measure: Efficacy as assessed by percent change in the American College of Rheumatology (ACR) score
timeFrame: up to 169 days
Other outcomes:
Locations:
city: Glendale
country: United States
state: Arizona
city: Aventura
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Lexington
country: United States
state: Kentucky
city: Baton Rouge
country: United States
state: Louisiana
city: Worcester
country: United States
state: Massachusetts
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.