Study of MDX-1100 (Anti-CXCL10 Human Monoclonal Antibody) in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (RA) (MDX1100-04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01017367
Recruitment Status : Completed
First Posted : November 20, 2009
Last Update Posted : April 23, 2010
Information provided by:
Bristol-Myers Squibb

Brief Summary:

The purpose of this study is to:

  1. determine the American College of Rheumatology (ACR) 20 response rate at Day 85 in subjects with active rheumatoid arthritis(RA) administered MDX 1100 with methotrexate (MTX); and
  2. determine the tolerability and safety of multiple doses of MDX-1100 in combination with MTX in subjects with active RA.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: MDX-1100 Drug: Placebo Phase 2

Detailed Description:

This Phase 2, double-blind, placebo-controlled, randomized, multi-dose, multicenter study of MDX 1100 (anti CXCL10 human monoclonal antibody) in combination with MTX in subjects with active RA. All subjects will continue to receive stable doses of MTX (10 to 25 mg weekly) during the study. Eligible subjects (n=70) will be randomized to receive either placebo (n=35) or MDX-1100 (n=35) at 10 mg/kg intravenously, every other week for a total of 6 doses. Concomitant treatment with stable doses of prednisolone (≤ 10 mg/d, or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDS) and analgesic drugs will be permitted during the study, however, the dose should not be changed until after the Day 85 assessment has been completed unless rescue therapy is required for significant worsening symptoms prior to Day 85. After Day 85, subjects will be followed until Day 141 only for safety and pharmacokinetics, and changes to baseline medications or addition of new medication will be permitted at the Investigator's discretion. Non-steroid anti-inflammatory drugs (NSAIDS) or analgesics should not be administered prior to disease activity assessments on study visit days.

Subjects withdrawn prior to Day 85 will be followed for safety for 70 days following their last dose of study drug.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 2, Multi-dose, Double-blind, Placebo-controlled, Randomized, Multicenter Study of MDX-1100 (Anti-CXCL10 Human Monoclonal Antibody) in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (RA)
Study Start Date : February 2008
Actual Primary Completion Date : January 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: MDX-1100
MDX-1100 10 mg/kg administered i.v. over 60 minutes on days 1, 15, 29, 43, 57, and 71
Drug: MDX-1100
MDX-1100 10 mg/kg i.v. over 60 minutes on days 1, 15, 29, 43, 57 and 71
Other Name: Anti CXCR4 Monocolonal anti-body, anti-IP-10

Placebo Comparator: Placebo
Placebo (saline) administered i.v. over 60 minutes on days 1, 15, 29, 43, 57, and 71
Drug: Placebo

Primary Outcome Measures :
  1. ACR 20 Response rate [ Time Frame: 85 days ]

Secondary Outcome Measures :
  1. Safety and tolerability will be monitored by physical exam, laboratory tests, electrocardiograms, chest x-ray and adverse events experienced and reported by the patient [ Time Frame: 141 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must meet the ACR criteria for RA
  • Must have active RA, characterized by at least 6 out of 66 swollen joints and 6 out of 68 tender joints, and at least 2 of the following: a serum C-reactive protein level greater than the upper limit of normal, an erythrocyte sedimentation rate >= 28 mm per hour, or morning stiffness > 45 minutes
  • Seropositive for rheumatoid factor, as defined by a plasma rheumatoid factor level of at least 20 IU per milliliter and/or be seropositive for anti-cyclic citrullinated peptide antibody
  • Must be on MTX (10 to 25 mg weekly) for at least 6 months receiving a stable dose for 42 days before randomization and no anticipated change in MTX dose while on study

    • Low-dose corticosteroids and NSAIDs are permitted at study entry and must have been stable for at least 28 days before randomization
    • All other disease modifying non-biologic anti-rheumatic drugs (DMARDs) must have been discontinued at least 28 days prior to randomization except for leflunomide (discontinued at least 60 days before randomization). Etanercept (discontinued at least 28 days prior to randomization) and infliximab, adalimumab, and abatacept (discontinued at least 56 days prior to randomization)
  • Screening laboratory values

    • Hemoglobin ≥ 8.5 g/dL
    • White blood cell (WBC) ≥ 3000/mm³
    • Neutrophils ≥ 1.5x10(9)/L
    • Platelets ≥ 125x10(9)/L
    • Serum creatinine < 2 mg/dL
    • Aspartate aminotransferase (AST) ≤ 2xULN
    • Alanine aminotransferase (ALT) ≤ 2xULN
  • Women must be postmenopausal (> 12 months without menses) or surgically sterile or using effective contraception for at least 4 weeks prior to the anticipated Visit 2 date and agree to continue contraception for the duration of their participation in the study
  • Sexually active male subjects must use a barrier method of contraception during the course of the study.

Exclusion Criteria:

  • Prior treatment with B cell depleting therapy
  • Any other monoclonal antibody or immunoglobulin-based fusion proteins ≤ 8 weeks prior to randomization
  • Any other experimental treatment ≤ 4 weeks prior to randomization
  • Primary or secondary immunodeficiency
  • Any other autoimmune disease other than RA (except concurrent Sjogren's syndrome or hypothyroidism)
  • Complications of RA including:

    • Active rheumatoid vasculitis
    • Bed bound or wheelchair bound
    • Clinically significant pulmonary fibrosis
    • Felty's syndrome
  • Any history of malignancy, excluding adequately treated and cured basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ
  • Active major psychiatric disease
  • Evidence of acute or chronic infection
  • Clinically significant cardiac disease requiring medication, unstable angina, myocardial infarction within 6 months of randomization, or congestive heart failure
  • Arrhythmia requiring active therapy, with the exception of clinically insignificant extrasystoles, or minor conduction abnormalities;
  • History of cerebrovascular disease requiring medication/treatment;
  • Concomitant anticoagulation therapy or a known bleeding disorder
  • Seizure disorder requiring active therapy
  • Known drug or alcohol abuse
  • Pregnant or nursing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01017367

Brasov Clinical County Emergency Hospital Rheumatology Department
Brasov, Romania, 500365
"Dr. Carol Davila" Central Military Emergency Clinical Hospital
Bucharest, Romania, 010825
Sana Medical Center
Bucharest, Romania, 011025
"Sf. Maria" Clinical Hospital, Department of Internal Medicine and Rheumatology
Bucharest, Romania, 011172
"Sf. Pantelimon" Emergency Clinical Hospital
Bucharest, Romania, 21659
Cluj Emergency County Clinical Hospital Rheumatology Department
Cluj-Napoca, Romania, 400006
Rehabilitation Hospital, Rheumatology Department
Iasi, Romania, 700656
Targu-Mures County Clinical Hospital Rheumatology Department
Targu-Mures, Romania, 540136
SC Excentric Company SRL, Rheumatology Department
Timisoara, Romania, 300449
M. Gorky National Medical University
Donetsk, Ukraine, 83003
V.K. Gusak Institute of Urgent & Reconstructive Surgery within the Academy of Medical Sciences of Ukraine, Hospital Therapy and Rehabilitation Clinic
Donetsk, Ukraine, 83045
Kharkiv Medical Academy of Postgraduate Education, Department of Cardiology and Functional Diagnostics, Clinical Facility: City Clinical Hospital #8
Kharkiv, Ukraine, 61178
Kyiv City Oleksandrivska Clinical Hospital, Rheumatology Department #2
Kyiv, Ukraine, 01601
O.O. Bogomolets National Medical University, Department of Internal Diseases Propedeutics #2, Clinical facility: City Clinical Hospital #3
Kyiv, Ukraine, 02125
Danylo Halytsky Lviv National Medical University, Department of Clinical Immunology and Allergology, Clinical Facility: Lviv Regional Clinical Hospital, Rheumatology Department
Lviv, Ukraine, 79010
Danylo Halytsky Lviv National Medical University, Department of Internal Diseases #2, Dermatology and Venerology within the Faculty of Continuing Education, Clinical facility: City Clinical Hospital #4, Rheumatology Department
Lviv, Ukraine, 79014
Public Institution O.I. Minakov City Clinical Hospital #9, Rheumatology Department
Odesa, Ukraine, 65026
Zaporizhya State Medical University, Department of Internal Diseases #2, Clinical facility: Medical and Sanitary Unit within the State-Owned Company "Radioprylad"
Zaporizhya, Ukraine, 69118
Sponsors and Collaborators
Bristol-Myers Squibb
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb. Identifier: NCT01017367     History of Changes
Other Study ID Numbers: MDX1100-04
IM129-003 ( Other Identifier: BMS )
First Posted: November 20, 2009    Key Record Dates
Last Update Posted: April 23, 2010
Last Verified: April 2010

Keywords provided by Bristol-Myers Squibb:
inflammatory joint disease

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors