Efficacy Study of MM-093 in Rheumatoid Arthritis Patients on Methotrexate (MTX)

A Phase 2, Double-Blind, Parallel, Placebo-Controlled, Randomized Study to Evaluate the Efficacy and Safety of 3 Different Dose Levels (2.5, 7.5 and 20 mg) of MM-093 in Patients With Active Rheumatoid Arthritis on Stable Doses of Methotrexate

The purpose of this clinical study is to see if an experimental drug, called MM-093, is safe and effective in the treatment of rheumatoid arthritis. MM-093 is a genetically engineered version of a naturally occurring protein called alpha fetoprotein (AFP). Adults normally have very small amounts of AFP in their bloodstream. However, during pregnancy, AFP levels in both the mother and the fetus are much higher than normal. It has been observed that women with RA (Rheumatoid Arthritis) have fewer symptoms during pregnancy, particularly during the third trimester. At this time, the levels of AFP in the blood of the mother and fetus are the highest. This observation led researchers to begin examining AFP as a possible treatment for RA.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: MM-093

• Study Type: Interventional
• Enrollment: 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama
    • Montgomery, Alabama, United States, 36111
      • Montgomery Rheumatology Associates
  • Arizona
    • Paradise Valley, Arizona, United States, 85253
      • Arizona Arthritis Research, PLC
    • Phoenix, Arizona, United States, 85012
      • ArthroCare, Arthritis Care and Research, Inc.
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research
  • California
    • Santa Maria, California, United States, 93454
      • Arthritis Medical Center of the Central Coast
    • Upland, California, United States, 91786
      • Boling Clinical Trials
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • New England Research Associates
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Ormond Beach, Florida, United States, 32174
      • International Medical Research
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
    • South Miami, Florida, United States, 33143
      • Center for Arthritis and Rheumatic Diseases
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Coeur D'Alene Arthritis Clinic
  • Illinois
    • Morton Grove, Illinois, United States, 60016
      • Illinois Bone and Joint Institute
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Rheumatology Associates, Pc
  • Kansas
    • Wichita, Kansas, United States, 67208
      • Wichita Clinic
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Rx Trials, Inc.
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Arthritis Center of Nebraska
  • Nevada
    • Reno, Nevada, United States, 89502
      • Arthritis Center of Reno
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • Arthritis, Osteoporosis & Musculoskeletal Disease Center
  • New York
    • Syracuse, New York, United States, 13210
      • Arthritis Health Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Rheumatology and Osteoporosis Research Associates, Inc
    • Charlotte, North Carolina, United States, 28210
      • Arthritis Clinic and Carolina Bone and Joint PA
    • Raleigh, North Carolina, United States, 27609
      • CARE Center
    • Raleigh, North Carolina, United States, 27609
      • North Carolina Arthritis and Allergy Care Center
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Veterans Administration Research Services
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Willow Grove, Pennsylvania, United States, 19090
      • Rheumatic Disease Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • The Arthritis Group
  • Texas
    • Austin, Texas, United States, 78705
      • Austin Rheumatology Research
    • Houston, Texas, United States, 77074
      • Houston Institute for Clinical Research
    • Waco, Texas, United States, 76708
      • Arthritis And Osteoporosis Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Division of Rheumatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-80 years
• Meet ACR (American College of Rheumatology) criteria for RA
• Have active RA consisting of 6 or more swollen and 6 or more tender joints
• Have RA for at least 6 months
• Had disease onset after 16 years old
• Currently being treated with a stable, well-tolerated dose of MTX (10 to 25 mg) given once weekly for at least 6 consecutive weeks prior to the screening visit
• Currently being treated with folic acid
• Willing to remain on a constant, once-weekly dose of MTX and folic/folinic acid throughout the duration of the study.
• Understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed.
• Be able and willing to comply with study visits and procedures per protocol.
• Sexually active men must agree to use a medically acceptable form of contraception during the study and continue for 4 weeks after the last dose of study drug.
• Women of childbearing potential must use a medically acceptable means of birth control during the study and for 4 weeks after the last dose
• Must be able to store study drug in a refrigerator at home

Exclusion Criteria:

• Use of any B-cell depleting therapy in the last 6 months
• Use of Leflunomide or Humira in the last 3 months
• Use of any investigational drug or biologic agent in the last 2 months
• Use of Remicade in the last 2 months
• Use of cyclosporine, sulphasalazine, auranofin, intramuscular gold, azathioprine, D-penicillamine or tacrolimus within the last 6 weeks
• Use of more than 10 mg/day of prednisone or equivalent in the last 4 weeks
• Use of intra-articular corticosteroid injection in the last 4 weeks
• Use of a bolus IM/IV (intramuscular/intravenous) treatment with corticosteroids (>20 mg prednisone or equivalent) in the last 4 weeks
• Use of Enbrel in the last 4 weeks
• Use of Kineret in the last 2 weeks
• Current use of more than 1 NSAID (non-steroidal anti-inflammatory drug) or dose of NSAID greater than the maximum recommended dose in the product information
• Cancer, or a history of cancer (other than successfully resected cutaneous basal and squamous cell carcinoma) within 5 years before the screening visit.
• Any condition for which participation in this study is judged by the physician to be detrimental to the patient, such as history of significant or unstable cardiac, pulmonary, gastrointestinal, neurological, or psychiatric disease, or a DMARD (Disease-Modifying Anti-Rheumatic Drug)-related severe, potentially life-threatening AE (Adverse Event).
• Significant ongoing infection requiring systemic antibiotic, antifungal, antiviral, or any anti-mycobacterial therapy.
• Autoimmune or connective tissue disorder other than rheumatoid arthritis (e.g. systemic lupus erythematosis, scleroderma or psoriatic arthritis).
• Grade 2 or above leukopenia (i.e. white blood cells < 3000/mm3 [SI units: < 3.0 x 10^9/L]).
• Thrombocytopenia or thrombocytosis (platelets < 125,000/mm3 or ≥ 1,000,000/mm3 [SI units: < 125 x 10^9/L or ≥ 1,000 x 10^9/L]), respectively.
• Grade 2 or above liver function abnormality (i.e. total bilirubin > 1.5 x the upper limit of normal; or aspartate aminotransferase [AST/SGOT] or alanine aminotransferase [ALT/SGPT] > 2.5 x upper limit of normal).
• Renal disease (including serum creatinine level > 1.5 x the upper limit of normal).
• Any history of immunodeficiency syndromes or infection with human immunodeficiency virus (HIV), or a history of hepatitis C or chronic hepatitis B.
• Pregnant or breastfeeding women or women planning to become pregnant during the study or within 4 weeks after the last dose of study drug.
• Any major surgery, including joint surgery, within 3 months before screening visit.
• Scheduled elective surgery during study participation.
• Participated in any previous clinical trial using MM-093 or have any prior exposure to MM-093.
• History of severe hypersensitivity to goat, sheep or cow milk or products derived from goat, sheep or cow milk (patients who are lactose intolerant are not excluded).
• Any other condition that the investigator feels would jeopardize the integrity of the study (e.g. a CTCAE [Common Terminology Criteria for Adverse Events] grade 2 or above clinical finding or laboratory result).

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To evaluate the efficacy of 3 different dose levels of MM-093 as measured by the percentage of patients achieving an ACR20 response after 24 weeks compared to placebo
To evaluate the safety and tolerability of 3 different dose levels of MM-093

Collaborators and Investigators

• Sponsor: Merrimack Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2005

Study Registration Dates

• First Submitted: March 18, 2005
• First Submitted That Met QC Criteria: March 18, 2005
• First Posted (Estimate): March 21, 2005

Study Record Updates

• Last Update Posted (Estimate): July 11, 2008
• Last Update Submitted That Met QC Criteria: July 10, 2008
• Last Verified: July 1, 2008

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
• Other Study ID Numbers: MM-093-01-200