Effects of MEDI-522 On Disease Activity and Progression of Joint Damage in Patients With Active Rheumatoid Arthritis Suboptimally Responding to Methotrexate

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00069017
• Other study ID #: MI-CP100
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2003
• Last updated: November 26, 2007
• Start date: September 2003
• Est. completion date: April 2006

Study information

• Verified date: November 2007
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• MEDI-522
MEDI-522 is formulated in a sterile isotonic solution of 10 mM histidine-HCl at pH 6 containing 100 mg of MEDI-522 protein at a concentration of 100 mg/mL.

Other:
• Placebo
Placebo for MEDI-522 contains 10 mM histidine-HCl at pH 6, 0.1% Tween-80, 1.5% Mannitol, 4.3 µg/mL Vitamin B12, and 2 µg/mL D&C Yellow #10.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada,