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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00105976
• Other study ID #: MM-093-01-200
• Status: Completed
• Phase: Phase 2
• First received: March 18, 2005
• Last updated: July 10, 2008
• Start date: February 2005

Study information

• Verified date: July 2008
• Source: Merrimack Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MM-093

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merrimack Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	To evaluate the safety and tolerability of 3 different dose levels of MM-093