A Seamless, Phase 1/2, Multiple Ascending Dose, Proof of Concept Study of ATN-103Administered to Subjects With Active Rheumatoid Arthritis on a Background ofMethotrexate

• Conditions: Rheumatoid arthritis; MedDRA version: 12.0Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2008-007185-33-GB
• Lead Sponsor: Wyeth Pharmaceuticals Inc., Acting through its division Wyeth Research, a Pfizer Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-07-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Male and female subjects between the ages of = 18 years and = 80 years at the time of signing the ICF.
2. Meets the American College of Rheumatology (ACR, formerly American Rheumatism
Association) 1987 revised criteria for classification of RA at least 24 weeks prior to
screening.
3. ACR functional class I to III.
4. Active RA at the time of screening and at baseline consisting of = 6 swollen and
= 6 tender joints (28-joint count).
5. The hs-CRP = 8 mg/L (.8 mg/dL) at screening (as determined by blood specimen sent to the Central Lab). The screening hs-CRP may be repeated once during the screening period.
6. Must be receiving MTX for at least 12 weeks, with a stable dose and route of MTX
(7.5 - 25 mg weekly) for at least 6 weeks prior to baseline and continuing on that dose for the duration of the study.
7. The report of a chest radiograph performed within 12 weeks of the screening visit (chest radiograph must be performed during the screening if no prior chest radiograph report is available) documenting the absence of any evidence of malignancy, infection, or abnormalities suggestive of tuberculosis must be obtained and available in the subject’s study file prior to baseline.
8. All women of childbearing potential (WOCBP) must have a negative serum pregnancy test result at screening and a negative urine pregnancy test result at baseline.
? WOCBP are defined as women who are biologically capable of becoming pregnant,
including women who are using contraceptives or whose sexual partners are either
sterile or using contraceptives.
? Women of non-childbearing potential (WONCBP) are defined as either
postmenopausal (history of amenorrhea for = 52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed = 52 weeks before screening). This information must be documented in the subject’s source documents.
? WONCBP do not require a serum and urine pregnancy test.
9. WOCBP who have sexual intercourse with a non-surgically sterilized male must agree and commit to the use of the following highly effective methods of contraception for duration of the study (defined as the time of the signing of the ICF through the conclusion of subject participation). Contraceptive methods considered acceptable for use in this study include:
•Established use of oral, injected or implanted hormonal methods of contraception.
•Double barrier contraception: Use of occlusive diaphragm (cap or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
•Intrauterine device or system
10. All men (unless surgically sterile, as defined below) who have sexual intercourse with a WOCBP must agree and commit to use a highly effective methods of contraception for the duration of the study (defined as the time of the signing of the ICF through the conclusion of subject participation). Highly effective methods of contraception include properly used spermicidal condom.
•To be considered surgically sterilized, a male partner must have had a vasectomy at least 24 weeks before study day 1
11. Willingness and ability to participate in all aspects of the study, including SC
administration of investigational product (by unblinded study personnel), completion of subject assessments, attending scheduled clinic visits, and compliance with all protocol requirements as evidenced by written informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18

Exclusion Criteria

1. Pregnant women or nursing mothers.
2. Presence of active infections, fungal infections (minor nail and skin infections will be allowed, ie, Tinea Pedis), or open cutaneous ulcers, any underlying diseases that could predispose subjects to infections, or history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks of baseline visit.
3. Significant concurrent, medical conditions at the time of screening or baseline visit
including, but not limited to:
? Any major illness/condition or evidence of an unstable clinical condition, such as,
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, immunologic
(eg, Felty’s syndrome, human immunodeficiency virus [HIV], infections,
neurological, cerebral psychiatric disease, or evidence of demyelinating disease
which, in the investigator’s judgment, will substantially increase the risk associated with the subject developing an adverse event (AE) or serious adverse event (SAE)
during the study, or preclude the evaluation of the subject’s response.
? A history or current evidence of latent or active tuberculosis infection, evidence of prior or currently active tuberculosis by chest radiography, recent close contact with an individual with active tuberculosis. Subjects who have a positive Mantoux (PPD) tuberculin skin test during screening or within 12 weeks prior to randomization. Documentation of the dose and product used as well as the official test reading must be obtained and available in the subject’s study file.
A positive Mantoux tuberculin skin test is defined as = 5 mm of induration (or as defined by country specific or local standards) at 48-72 hours without consideration of prior Bacillus Calmette-Guérin (BCG) vaccination. However, if the results of the Mantoux tuberculin skin test are thought to represent a false positive eg, < 10 mm, induration possibly due to prior BCG vaccination then performing Interferon Gamma Release Assay (the following are acceptable assays, Quantiferon or T-spot) test is appropriate and must be negative or the patient is excluded. Documentation of prior BCG vaccination and timing (if known), the IGRA product used, the reason for using it and the test result, should be in the subject’s study file.
? A history or suspicion (received antibiotics) of a joint prosthesis infection if
prosthesis not removed or replaced.
? Any rheumatologic disease other than RA, including but not limited to Lyme disease, primary Sjögren’s syndrome, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious arthritis, reactive arthritis (Reiter’s syndrome), or scleroderma.
? Current or history of cancer or lymphoproliferative disease within previous 5 years (resected cutaneous basal cell or squamous cell carcinoma are exempt from time limit) that has been treated with no evidence of recurrence.
? Class III or IV congestive heart failure as defined by the New York Heart Association
? Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris) and
any history of significant cerebrovascular disease within 24 weeks of screening.
? Have a transplanted organ.
? Documented history of any drug-induced liver injury, liver cirrhosis, or fibrosis at any time before baseline visit.
4. Abnormality in hematology or biochemistry profiles at screening:
? Positive hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis C antibody (HepCAb) w

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified