Clinical trial NCT00105976: Efficacy Study of MM-093 in Rheumatoid Arthritis Patients on Methotrexate (MTX)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Merrimack Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2005-03-21
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
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
measure: To evaluate the safety and tolerability of 3 different dose levels of MM-093
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Montgomery
country: United States
facility: Montgomery Rheumatology Associates
state: Alabama
city: Paradise Valley
country: United States
facility: Arizona Arthritis Research, PLC
state: Arizona
city: Phoenix
country: United States
facility: ArthroCare, Arthritis Care and Research, Inc.
state: Arizona
city: Scottsdale
country: United States
facility: Radiant Research
state: Arizona
city: Santa Maria
country: United States
facility: Arthritis Medical Center of the Central Coast
state: California
city: Upland
country: United States
facility: Boling Clinical Trials
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Bridgeport
country: United States
facility: New England Research Associates
state: Connecticut
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialties
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Ormond Beach
country: United States
facility: International Medical Research
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: South Miami
country: United States
facility: Center for Arthritis and Rheumatic Diseases
state: Florida
city: Coeur d'Alene
country: United States
facility: Coeur d'Alene Arthritis Clinic
state: Idaho
city: Morton Grove
country: United States
facility: Illinois Bone and Joint Institute
state: Illinois
city: Springfield
country: United States
facility: The Arthritis Center
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates
state: Illinois
city: Indianapolis
country: United States
facility: Rheumatology Associates, PC
state: Indiana
city: Wichita
country: United States
facility: Wichita Clinic
state: Kansas
city: Columbia
country: United States
facility: Rx Trials, Inc.
state: Maryland
city: Lincoln
country: United States
facility: Arthritis Center of Nebraska
state: Nebraska
city: Reno
country: United States
facility: Arthritis Center of Reno
state: Nevada
city: Concord
country: United States
facility: Arthritis, Osteoporosis & Musculoskeletal Disease Center
state: New Hampshire
city: Syracuse
country: United States
facility: Arthritis Health Associates
state: New York
city: Asheville
country: United States
facility: Asheville Rheumatology and Osteoporosis Research Associates, Inc
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis Clinic and Carolina Bone and Joint PA
state: North Carolina
city: Raleigh
country: United States
facility: CARE Center
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Arthritis and Allergy Care Center
state: North Carolina
city: Cincinnati
country: United States
facility: Veterans Administration Research Services
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Memphis
country: United States
facility: The Arthritis Group
state: Tennessee
city: Austin
country: United States
facility: Austin Rheumatology Research
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Waco
country: United States
facility: Arthritis and Osteoporosis Clinic
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Division of Rheumatology
state: Utah
Study officials:
References: