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

NCT01017367 | Completed Phase 2 DMC

• 2 other identifiers: MDX1100-04IM129-003
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 18

Brief Summary

The purpose of this study is to:

1. 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. 2.determine the tolerability and safety of multiple doses of MDX-1100 in combination with MTX in subjects with active RA.

Conditions

Rheumatoid Arthritis

Keywords

RA; inflammatory joint disease

Outcome Measures

Primary Outcomes (1)

• ACR 20 Response rate

  85 days

Secondary Outcomes (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

  141 days

Study Arms (2)

MDX-1100

EXPERIMENTAL

MDX-1100 10 mg/kg administered i.v. over 60 minutes on days 1, 15, 29, 43, 57, and 71

Drug: MDX-1100

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

MDX-1100 DRUG

MDX-1100 10 mg/kg i.v. over 60 minutes on days 1, 15, 29, 43, 57 and 71

Also known as: Anti CXCR4 Monocolonal anti-body, anti-IP-10

MDX-1100

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (18)

Brasov Clinical County Emergency Hospital Rheumatology Department

Brasov, 500365, Romania

Location

"Dr. Carol Davila" Central Military Emergency Clinical Hospital

Bucharest, 010825, Romania

Location

Sana Medical Center

Bucharest, 011025, Romania

Location

"Sf. Maria" Clinical Hospital, Department of Internal Medicine and Rheumatology

Bucharest, 011172, Romania

Location

"Sf. Pantelimon" Emergency Clinical Hospital

Bucharest, 21659, Romania

Location

Cluj Emergency County Clinical Hospital Rheumatology Department

Cluj-Napoca, 400006, Romania

Location

Rehabilitation Hospital, Rheumatology Department

Iași, 700656, Romania

Location

Targu-Mures County Clinical Hospital Rheumatology Department

Târgu Mureş, 540136, Romania

Location

SC Excentric Company SRL, Rheumatology Department

Timișoara, 300449, Romania

Location

M. Gorky National Medical University

Donetsk, 83003, Ukraine

Location

V.K. Gusak Institute of Urgent & Reconstructive Surgery within the Academy of Medical Sciences of Ukraine, Hospital Therapy and Rehabilitation Clinic

Donetsk, 83045, Ukraine

Location

Kharkiv Medical Academy of Postgraduate Education, Department of Cardiology and Functional Diagnostics, Clinical Facility: City Clinical Hospital #8

Kharkiv, 61178, Ukraine

Location

Kyiv City Oleksandrivska Clinical Hospital, Rheumatology Department #2

Kyiv, 01601, Ukraine

Location

O.O. Bogomolets National Medical University, Department of Internal Diseases Propedeutics #2, Clinical facility: City Clinical Hospital #3

Kyiv, 02125, Ukraine

Location

Danylo Halytsky Lviv National Medical University, Department of Clinical Immunology and Allergology, Clinical Facility: Lviv Regional Clinical Hospital, Rheumatology Department

Lviv, 79010, Ukraine

Location

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, 79014, Ukraine

Location

Public Institution O.I. Minakov City Clinical Hospital #9, Rheumatology Department

Odesa, 65026, Ukraine

Location

Zaporizhya State Medical University, Department of Internal Diseases #2, Clinical facility: Medical and Sanitary Unit within the State-Owned Company "Radioprylad"

Zaporizhya, 69118, Ukraine

Location

Related Publications (1)

• Yellin M, Paliienko I, Balanescu A, Ter-Vartanian S, Tseluyko V, Xu LA, Tao X, Cardarelli PM, Leblanc H, Nichol G, Ancuta C, Chirieac R, Luo A. A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2012 Jun;64(6):1730-9. doi: 10.1002/art.34330. Epub 2011 Dec 6.

  PMID: 22147649 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

MDX-1100

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 20, 2009
• Study Start: February 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: May 1, 2009
• Last Updated: April 23, 2010

Record last verified: 2010-04

Locations

RO (9); UA (9)