Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II/III, Multicenter, Randomized, Double-Blind, Double-Dummy Study to Assess Similarity of the Efficacy, Pharmacokinetics, Safety and Immunogenicity of Abatacept Administered Subcutaneously or Intravenously in Japanese Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
Brief Summary: The purpose of this study is to assess the efficacy, pharmacokinetics, safety, and immunogenicity of abatacept after subcutaneous and intravenous administration in Japanese participants with active rheumatoid arthritis and inadequate response to methotrexate.


Options:
A: Inclusion Criteria:

* adult patients at least 18 years of age with active RA for at least 3 months;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study or planned major surgery within 6 months after entering study;
* treatment with methotrexate (MTX) within 6 months of entering study;
* patients who have stopped previous MTX treatment due to toxicity or lack of response;
* women who are pregnant or breast-feeding.
B: Inclusion Criteria:

* Patients must be at least 18 years old at the screening visit.
* Patients must have a diagnosis of adult-onset RA of at least six months duration but not longer than fifteen years as defined by the 1987 American College of Rheumatology classification criteria.
* Patients must have active RA disease as defined by:

  * 9 tender joints at Screening and Baseline.
  * 9 swollen joints at Screening and Baseline. and fulfilling 1 of the following 2 criteria during the screening period:
  * 30 mm/hour ESR (Westergren), or CRP \>15 mg/L.
* Patients must have received treatment with MTX (with or without folic acid) for at least 6 months prior to the Baseline visit. The dose of MTX and route of administration must have been stable for at least 2 months prior to the baseline visit. The minimum stable dose of MTX allowed is 10 mg weekly.
* Patients must be willing to complete an X-ray of the hands and feet 24 weeks after randomization even if they are no longer receiving study treatment in the present study, provided they have not withdrawn their informed consent.

Exclusion Criteria:

* Patients must not have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
* Patients must not have a secondary, non-inflammatory type of arthritis (e.g. OA or fibromyalgia)
* Female patients who are breast feeding, pregnant, or plan to become pregnant during the trial or for three months following last dose of study drug.
* Patients with a history of tuberculosis or positive chest X-ray for tuberculosis or positive
* Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bed ridden or wheelchair bound).
* Patients with known human immunodeficiency virus (HIV) infection.
* Patients with an active malignancy of any type or a history of malignancy (except basal cell carcinoma of the skin that has been excised prior to study start).
* Patients with a current or recent history, as determined by the Investigator, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease which would interfere with the patient's participation in the trial.
* Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
C: Key Inclusion Criteria:

* Meeting criteria of the American Rheumatism Association for the diagnosis of rheumatoid arthritis (RA) and the American College of Rheumatology functional Classes I, II, or III.
* Inadequate response (as deemed by investigator) to methotrexate taken for at least 3 months (12 weeks) at a stable dose (6 to 8 mg/week) for 28 days prior to randomization (Day 1).
* Stabilization requirements for concomitant therapy: Oral corticosteroid treatment reduced to the equivalent of ≤10 mg prednisolone daily for 28 days and stabilized for at least 25 of 28 days prior to treatment (Day 1). No intra-articular, intravenous, or intramuscular injections of corticosteroids were permitted within 28 days prior to randomization (Day 1.)
* Washout requirements: Participants receiving combination RA therapy had to discontinue the following therapies at least 28 days prior to treatment (Day 1):

disease-modifying antirheumatic drugs (DMARDs), such as gold (auranofin and aurothiomalate sodium), actarit, bucillamine, azathioprine, salazosulfapyridine, lobenzarit disodium, D-penicillamine, cyclophosphamide, mycophenolate mofetil, mizoribine; cyclosporin, tacrolimus, and other calcineurin inhibitors; and immunoadsorption columns.

* Disease Activity Requirements: At randomization (Day 1), participants had to meet the following disease activity criteria: Swollen joint count: 10 or more swollen joints (66 joint count); tender joint count: 12 or more tender joints (68 joint count); C reactive protein (CRP): ≥0.8 mg/dL (result from screening visit).
* For participants receiving methotrexate plus other DMARDs(washout of a combination therapy required): At screening visit, participants had to meet the following disease activity criteria: Swollen joint count: 6 or more swollen joints (66 joint count); tender joint count: 8 or more tender joints (68 joint count); CRP: no restriction on CRP (not applicable).
* After washout, at randomization (Day 1), participants must meet the following disease activity criteria: Swollen joint count-10 or more swollen joints (66 joint count) and tender joint count-12 or more tender joints (68 joint count) and CRP: ≥0.8 mg/dL (result from screening visit). For those whose screening period were longer than 4 weeks, CRP test needed to be performed on Day
* 28 to Day -3 (prior to treatment Day 1) to verify eligibility.

Key Exclusion Criteria:

* Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease. Concomitant medical conditions that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this study.
* Female participants who had undergone breast cancer screening that was suspicious for malignancy, and in whom the possibility of malignancy could not be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations.
* History of cancer within the last 5 years (other than nonmelanoma skin cell cancers cured by local resection)
* Existing nonmelanoma skin cell cancers had been removed prior to the first administration. Participants with carcinoma in situ, treated with definitive surgical intervention prior to study entry were allowed to participate.
* Clinically significant drug or alcohol abuse
* Any serious acute bacterial infection (such as pneumonia or pyelonephritis unless treated and completely resolved with antibiotics)
* Serious, chronic, or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis)
* Those at risk for tuberculosis (TB). Specifically, those with current clinical, radiographic, or laboratory evidence suggestive of active TB; history of active TB within the last 3 years, even if treated; history of active TB more than 3 years ago unless there was documentation that the prior anti-TB treatment was appropriate in type and duration; latent TB that was not successfully treated. Participants with a positive result on TB screening test indicative of latent TB were not eligible for the study unless active TB infection had been ruled out and treatment for latent TB with isoniazid had been initiated for at least 4 weeks prior to administration of the study drug and the participant had a negative finding for TB on a chest X-ray film at enrollment.
* Herpes zoster resolving less than 2 months prior to enrollment
* Current evidence (as assessed by the investigator) suggestive of active or latent bacterial or viral infections, including human immunodeficiency virus infection.
* Physical examination and laboratory test findings: Hepatitis B surface antigen-positive status; hepatitis C antibody-positive status. Any of the following laboratory values: Hemoglobin concentration: \<.5 g/dL; white blood cell count: \<3,000/μL (3\*10\^9/L); platelet count: \<100,000/mm\^3(100\*10\^9/L); serum creatinine: \>2 times upper limit of normal (ULN); serum alanine aminotransferase: \>2 ULN; serum aspartate aminotransferase: \>2 ULN.
* Prohibited treatments and/or therapies: Prior exposure to abatacept (CTLA4-Ig); prior RA treatment with any biologics, such as anti-tumor necrosis factor therapy; prior exposure to any investigational biologic not currently approved in Japan; exposure to any study medication in any other previous study within 4 weeks or 5 half-lives, whichever was longer; receipt of any live vaccines within 3 months of administration of study medication or scheduled to receive live vaccines.
D: Inclusion Criteria:

* adult patients at least 18 years of age with moderate to severe active RA for at least 6 months;
* inadequate response to a stable dose of MTX;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
* prior treatment failure with an anti-tumor necrosis factor agent;
* women who are pregnant or breast-feeding.

Answer: C