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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01017367
First received: November 16, 2009
Last updated: April 22, 2010
Last verified: April 2010
  Purpose

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 Intervention Phase
Rheumatoid Arthritis
Drug: MDX-1100
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • ACR 20 Response rate [ Time Frame: 85 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 70
Study Start Date: February 2008
Study Completion Date: May 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01017367

Locations
Romania
Brasov Clinical County Emergency Hospital Rheumatology Department
Brasov, Romania, 500365
Sana Medical Center
Bucharest, Romania, 011025
"Dr. Carol Davila" Central Military Emergency Clinical Hospital
Bucharest, Romania, 010825
"Sf. Pantelimon" Emergency Clinical Hospital
Bucharest, Romania, 21659
"Sf. Maria" Clinical Hospital, Department of Internal Medicine and Rheumatology
Bucharest, Romania, 011172
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
Ukraine
V.K. Gusak Institute of Urgent & Reconstructive Surgery within the Academy of Medical Sciences of Ukraine, Hospital Therapy and Rehabilitation Clinic
Donetsk, Ukraine, 83045
M. Gorky National Medical University
Donetsk, Ukraine, 83003
Kharkiv Medical Academy of Postgraduate Education, Department of Cardiology and Functional Diagnostics, Clinical Facility: City Clinical Hospital #8
Kharkiv, Ukraine, 61178
O.O. Bogomolets National Medical University, Department of Internal Diseases Propedeutics #2, Clinical facility: City Clinical Hospital #3
Kyiv, Ukraine, 02125
Kyiv City Oleksandrivska Clinical Hospital, Rheumatology Department #2
Kyiv, Ukraine, 01601
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
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb.
ClinicalTrials.gov Identifier: NCT01017367     History of Changes
Other Study ID Numbers: MDX1100-04, IM129-003
Study First Received: November 16, 2009
Last Updated: April 22, 2010
Health Authority: Romania: Ministry of Public Health
Romania: National Medicines Agency
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Bristol-Myers Squibb:
RA
inflammatory joint disease

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

ClinicalTrials.gov processed this record on April 16, 2014