Clinical trial NCT00069017: Effects of MEDI-522 On Disease Activity and Progression of Joint Damage in Patients With Active Rheumatoid Arthritis Suboptimally Responding to Methotrexate
Official title: A Phase II, Randomized, Double-Blind Study to Evaluate the Effects of MEDI-522, a Humanized MAb to Integrin Alpha V Beta 3, On Disease Activity and Progression of Joint Damage in Pts With Active Rheumatoid Arthritis Suboptimally Responding to Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2003-09-17
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To compare, as a preliminary analysis, the effects of MEDI-522 versus placebo at 6 months on disease activity (ACR20) and progression of structural joint damage.

Detailed description: To compare, as a preliminary analysis, the effects of subcutaneously administered MEDI-522 versus placebo at 6 months on disease activity and progression of structural joint damage in patients with rheumatoid arthritis (RA), who have active disease despite ongoing treatment with methotrexate (MTX) with or without hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ).

Eligibility criteria: Patients must meet all of the following criteria:

1. Age greater than or equal to 18 (reached 18th birthday or later) at the time of the first dose of study drug
2. Written informed consent obtained from the patient
3. Sexually active females, unless surgically sterile or at least one year post-menopausal, must use an effective method of avoiding pregnancy (including oral, transdermal, injectable, or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 21 days prior to the first dose of study drug, and must agree to continue using such precautions through 3 months after their last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
4. A diagnosis of RA as defined by American College of Rheumatology (ACR) criteria, which is currently active, as defined by the presence of at least 6 swollen and 6 tender joints involving the hands, wrists, elbows, knees, ankles, or feet and a CRP and/or ESR\>Upper Limits of Normal (ULN).
5. Treatment with a stable dose level and frequency of methotrexate for at least 8 weeks prior to study randomization. The patients may also be taking hydroxychloroquine and/or sulfasalazine concurrently with methotrexate. These drugs must also be at stable dose levels and frequencies for at least 8 weeks prior to randomization. Patients currently receiving treatment with stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, or prednisone (less than or equal to 10 mg/day) will be permitted to continue these medications. Analgesics, including acetaminophen, talwin, propoxyphene, tramadol hydrochloride, codeine or codeine with acetaminophen, hydrocodone, oxycontin, and related medications, will also be permitted. All of these drugs must be at stable dose levels and frequencies for at least 4 weeks prior to study randomization.
6. Prior to randomization (must be within 21 days of the first administration of the study drug), all of the following: WBC ≥ 3,800/mm³; platelet count ≥140,000/mm³; AST, ALT, BUN, or creatinine\<1.5 x ULN; stool negative for occult blood; and thyroxine (T4) within normal limits. (Patients with an elevated T4 but with both free T4 and TSH levels within normal limits may be eligible after review by the MedImmune medical monitor.)
7. Willing to forego other forms of experimental treatment during study through Study Day 364
8. Able and willing to complete assessment questionnaires.
9. Willing to participate in study through Study Day 413.

Exclusion Criteria

Patients must have none of the following:

1. Severe active RA, which in the opinion of the investigator currently requires an alternative form of therapy
2. Acute illness at the start of the study
3. Evidence of significant active infection, such as fever greater than or equal to 38.0°C (100.5°F)
4. Known or suspected infection with human immunodeficiency virus (HIV) or other evidence of clinically significant immune deficiencies
5. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, such as positive HBsAg or positive anti-hepatitis C antibody
6. Insulin-dependent diabetes mellitus that is recent-onset or unstable
7. Evidence of active or latent tuberculosis, which may include a positive PPD skin test result (greater than or equal to 10 mm induration), unless appropriate INH prophylaxis for tuberculosis previously given; a chest X-ray possibly consistent with tuberculosis; or household contact with a patient with active tuberculosis
8. A medical history or evidence of clinically important chronic infection, recurrent (3 or more) infections in the past 6 months requiring antibiotics, or an infection in the past month requiring systemic antibiotics
9. Receipt of any investigational drug therapy, except MEDI-522, within 3 months prior to study randomization (use of licensed agents for indications not listed in the package insert is permitted)
10. Current or any past therapy with anti-TNF biologic antagonists including etanercept, infliximab, and adalimumab
11. Current therapy with cyclosporin A, leflunomide, cyclophosphamide, azathioprine, gold salts, d-penicillamine, mycophenylate mofetil, minocycline or anakinra. These drugs must have been discontinued at least 4 weeks prior to study randomization.
12. Prednisone or equivalent at \>10 mg per day orally in the 8 weeks before study randomization. Intraarticular, periarticular, or other forms of parenteral injection of corticosteroids are also not permitted in the 8 weeks prior to study randomization.
13. History of allergic disease or reactions likely to be exacerbated by any component of MEDI-522
14. History of gastrointestinal bleeding (i.e., stool positive for occult blood or overt bleeding) within the previous 6 months
15. Known bleeding disorder or significant risk of clinically important abnormal bleeding due to anticoagulant therapy with warfarin or heparin
16. Elective surgery planned during the study period through Study Day 413
17. Cardiovascular disease that is unstable, such as recent-onset angina, or angina with increasing frequency or severity, or recent myocardial infarction (within past 1 year without definitive corrective surgery such as coronary bypass graft or angioplasty)
18. Neurological disease, such as multiple sclerosis, previous stroke, clinically significant cerebrovascular disease, or other forms of organic brain disease that is clinically significant
19. Pulmonary, hepatic, renal, or hematological disease that is unstable and progressive, or clinically severe
20. Pregnancy (all females, unless surgically sterile or at least one year post-menopausal, must have a negative urine pregnancy test on Study Day 0, prior to dosing)
21. Nursing mother
22. History of alcohol or drug abuse within past 2 years
23. Evidence on physical examination of rheumatoid or other types of vasculitis.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: Sun Valley Arthritis Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Research & Education
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Fayetteville
country: United States
facility: Fayetteville Diagnostic Clinic, Ltd.
state: Arkansas
city: La Jolla
country: United States
facility: Thornton Hospital
state: California
city: Rancho Cucamonga
country: United States
facility: Boling Clinical Trials
state: California
city: Santa Maria
country: United States
facility: Pacific Arthritis Center Medical Group
state: California
city: Aventura
country: United States
facility: Arthritis and Rheumatic Disease Specialty
state: Florida
city: Fort Lauderdale
country: United States
facility: Centre for Rheumatology, Immunology & Arthritis
state: Florida
city: Ocala
country: United States
facility: Ocala Rheumatology Research Center
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: Decatur
country: United States
facility: Sanford S. Hartman
state: Georgia
city: Wheaton
country: United States
facility: Center for Rheumatology and Bone Research
state: Maryland
city: St. Louis
country: United States
facility: RIMA
state: Missouri
city: St. Louis
country: United States
facility: Arthritis Consultants, Inc.
state: Missouri
city: Teaneck
country: United States
facility: Rheumatology Associates of New Jersey
state: New Jersey
city: Albany
country: United States
facility: The Center for Rheumatology
state: New York
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Center for Arthritis Therapy and Research Inc.
state: Oklahoma
city: Amarillo
country: United States
facility: Amarillo Center for Clinical Research
state: Texas
city: Dallas
country: United States
facility: Radiant Research
state: Texas
city: Lubbock
country: United States
facility: Arthritis & Osteoporosis Associates, LLP
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Hospital
state: Utah
city: Spokane
country: United States
facility: The Physician's Clinic of Spokane
state: Washington
city: Yakima
country: United States
facility: Rheumatology Northwest/Clinical Trials Northwest
state: Washington
city: La Crosse
country: United States
facility: Gundersen Clinic Ltd.
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
city: Richmond
country: Canada
facility: Richmond Health Science Center
state: British Columbia
city: Winnipeg
country: Canada
facility: Manitoba Clinic
state: Manitoba
city: Winnipeg
country: Canada
facility: Arthritis Centre
state: Manitoba
city: Winnipeg
country: Canada
facility: Centre Inflammatory Arthritis Disease Studies
state: Manitoba
city: Hamilton
country: Canada
facility: Charlton Medical Center
state: Ontario
city: Hamilton
country: Canada
facility: MAC Research, Inc.
state: Ontario
city: Kitchener
country: Canada
facility: K-W Musculoskeletal Research, Inc.
state: Ontario
city: Newmarket
country: Canada
facility: The Arthritis Program Research Group Inc.
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Rheumatic Disease Center of Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: Midtown Medical Center
state: Saskatchewan
Study officials:
References: