Trial With HuMax-CD4 in Participants With Rheumatoid Arthritis (RA) Failing Treatment With Methotrexate (MTX) and a TNF-alpha Blocker

A Double-Blind, Placebo-Controlled, Randomized, Parallel Group Clinical Trial of Anti-CD4 Receptor Human Monoclonal Antibody (HuMax-CD4) in Patients With Active Rheumatoid Arthritis Failing Treatment With Methotrexate and TNF-alpha Blocking Agents

The purpose of this study is to determine whether HuMax-CD4 is effective in the treatment of active RA in participants who have failed treatment with MTX and at least one TNF-alpha blocking agent.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: HuMax-CD4; Drug: Humax-CD4

Detailed Description

This is a multi-center, double-blind, placebo-controlled, parallel-group, randomized trial of HuMax-CD4 in the treatment of participants with active RA who have failed treatment with MTX and at least one TNF-alpha blocking agent. Participants are randomized to receive one of two doses of HuMax-CD4 or placebo. The drug will be administered as a subcutaneous infusion (given just under the skin), more often in the beginning and then followed by a maintenance dose. There is a 4 week follow up period, and the final evaluation of the clinical endpoints takes place 26 weeks after treatment start. The trial lasts about 28 weeks in all.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 3J5
      • CIADS, Medical Arts Building
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital-General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook/Women's College Research Health Science Center
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Institute de Rhumtologie de Montreal
• United States
  • Alabama
    • Montgomery, Alabama, United States, 36111-2654
      • Rheumatology Associates
  • California
    • Long Beach, California, United States, 90813-3412
      • Pro Health Partners, Inc.
    • Rancho Cucamonga, California, United States, 91730
      • Rheumatology & Internal Medicine, Boling Clinical Trials
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
    • San Diego, California, United States, 92108
      • Radiant Research, Inc.
    • Van Nuys, California, United States, 91405
      • West Coast Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Arthritis Center of CT
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Arthritis Associates of South Florida
    • Ocala, Florida, United States, 34474
      • Ocala Rheumatology Research Center
    • Saint Petersburg, Florida, United States, 33707
      • nTouch Research
    • Stuart, Florida, United States, 34996
      • Radiant Research, Inc.
    • Tampa, Florida, United States, 33614
      • Tampa Medical Group Research
  • Georgia
    • Decatur, Georgia, United States, 30033
      • nTouch Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • North Western Center for Clinical Research
    • Chicago, Illinois, United States, 60612
      • Rheumatology Associates, P.C.
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Indiana
    • Evansville, Indiana, United States, 47714
      • West Pharmaceutical Services
    • Meridian Hills, Indiana, United States, 83642
      • Idaho Arthritis & Osteoporosis Center
  • Iowa
    • Des Moines, Iowa, United States, 50322
      • Mercy Arthritis Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Osteoporosis and Clinical Trials Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Arthritis Education and Treatment Center
    • Kalamazoo, Michigan, United States, 49001
      • Midwest Arthritis Center
    • Lansing, Michigan, United States, 48910
      • Fiechtner Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Westroads Medical Group
  • Nevada
    • Reno, Nevada, United States, 89502
      • Arthritis Center of Reno
  • New York
    • Syracuse, New York, United States, 13210
      • One Crouse Medical Plaza
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • C.A.R.E. Center
  • Ohio
    • Canfield, Ohio, United States, 44406
      • DataPharm, Inc.
    • Cincinnati, Ohio, United States, 45219
      • Disease Study Group / Deaconess Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
    • Medford, Oregon, United States, 97504
      • Rheumatology Clinic
    • Portland, Oregon, United States, 97213
      • Providence Arthritis Center
    • Portland, Oregon, United States, 97225
      • Northwest Rheumatology Associates, PC
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Pennsylvania Rheumatology
    • Duncansville, Pennsylvania, United States, 16635-0909
      • Altoona Arthritis & Osteoporosis Center
    • West Reading, Pennsylvania, United States, 19611
      • Clinical Research Center of Reading
  • Texas
    • Dallas, Texas, United States, 75231
      • Presbyterian Hospital of Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • IHC Clinical Research Foundation
  • Virginia
    • Richmond, Virginia, United States, 23298-0647
      • Medical College of Virginia, Div. of Rheum.
    • Salem, Virginia, United States, 24153
      • Lewis Gayle Clinic
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Medical & Dental Center
    • Olympia, Washington, United States, 98502
      • South Puget Sound Clinical Research Center
    • Seattle, Washington, United States, 98104
      • Minor & James Med., First Hill Medical Building
    • Yakima, Washington, United States, 98902
      • Internal Medicine Association of Yakima, Inc., P.S.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Medical Arts Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A diagnosis of rheumatoid arthritis according to the American College of Rheumatology 1987 revised criteria (ACR) of at least 6 months duration.
• Active disease at the time of screening.
• Failure to tolerate MTX, or lack of efficacy after a minimum of 6 months treatment with MTX.

Exclusion Criteria:

• Active autoimmune disease requiring therapy (other than rheumatoid arthritis and secondary Sjögren's disease).
• Syndromes such as Fibromyalgia which require chronic pain treatment.
• Most past or current cancers.
• Chronic or current infectious disease such as, but not limited to, chronic renal infection, chronic chest, nasal or throat infections, tuberculosis, hepatitis B and C.
• History of infected joint prosthesis within 5 years.
• Most active medical conditions such as heart disease, kidney disease, liver disease, blood diseases, hormonal disturbances, lung disease, psychiatric disease.
• Drug or alcohol abuse.
• Pregnant or breast-feeding women may not participate. Women of childbearing potential must use either contraceptive pills or an intra-uterine device for the entire study period.

Note: Other protocol defined Inclusion and Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo was administered as a subcutaneous infusion twice (BID) with 2 weeks interval followed by administration every 4 weeks up to Week 22.
Experimental: HuMax-CD4 80 milligrams (mg)	Drug: HuMax-CD4; HuMax-CD4 80 mg was administered as a subcutaneous infusion BID with 2 weeks interval followed by administration every 4 weeks up to Week 22.; Other Names: Zanolimumab
Experimental: HuMax-CD4 160 mg	Drug: Humax-CD4; HuMax-CD4 160 mg was administered as a subcutaneous infusion BID with 2 weeks interval followed by administration every 4 weeks up to Week 22.; Other Names: Zanolimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with American College of Rheumatology (ACR) 20 Response	At Week 14 and Week 18
Change from Baseline in Disease Activity Score (DAS)	Baseline up to Week 26
Change from Baseline in SFP-36 questionnaire at Week 10 and 26	Baseline, Week 10 and Week 26
Change from Baseline in C-Reactive Protein (CRP)	Baseline up to Week 26
Change from Baseline in Erythrocyte Sedimentation Rate (ESR)	Baseline up to Week 26
Number of Participants with Adverse Events (AEs)	Day 1 up to end of study (Week 26)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Positive Human Anti Human Antibodies (HAHA) Titres	Up to 26 weeks
Number of Participants With Clinically Significant Laboratory Abnormalities	Up to 26 weeks

Collaborators and Investigators

• Sponsor: Genmab

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2002
• Primary Completion (Actual): March 31, 2003
• Study Completion (Actual): March 31, 2003

Study Registration Dates

• First Submitted: July 29, 2002
• First Submitted That Met QC Criteria: July 31, 2002
• First Posted (Estimate): August 1, 2002

Study Record Updates

• Last Update Posted (Actual): April 28, 2023
• Last Update Submitted That Met QC Criteria: April 26, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• 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; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antibodies, Monoclonal; Zanolimumab
• Other Study ID Numbers: Hx-CD4-004

Drug and device information, study documents

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