Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo Controlled, Multi-centre Phase II Study of Atacicept in Anti-TNFα-naïve Patients With Moderate to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Brief Summary: The primary objective of this study is to evaluate the efficacy of atacicept compared to placebo in the treatment of signs and symptoms in a subject population with active rheumatoid arthritis (RA), inadequate response to methotrexate (MTX) and no previous exposure to anti-tumor necrosis factor alpha (anti-TNFalpha) therapy.


Options:
A: Inclusion Criteria:

* Male or female subjects greater than or equal to (\>=) 18 years of age at the time of informed consent who have RA satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 6 months
* Subjects must have active disease, defined by \>=8 swollen joints (out of 66), \>=8 tender joints (out of 68) and CRP \>=10 milligram per liter (mg/L) and/or erythrocyte sedimentation rate (ESR) \>=28 millimeter per hour (mm/hr), despite treatment with MTX at a dose of \>=15 milligram per week (mg/week) for greater than (\>) 3 months
* Other protocol-defined inclusion criteria could apply

Exclusion Criteria:

* Inflammatory joint disease other than RA
* Previous or concurrent treatment with any approved or investigational biological compound for RA, including but not restricted to any anti-TNFalpha agents, rituximab, abatacept, tocilizumab, interleukin-1 receptor antagonist (IL-1Ra) and belimumab
* Treatment with disease-modifying anti-rheumatic drug (DMARDs) other than MTX
* Participation in any interventional clinical trial within 1 month before study Day 1
* MTX dose \>25 mg/week, prednisone dose \>10 mg/day (or equivalent), or change in steroid or non-steroidal anti-inflammatory drug (NSAID) dosing regimen within 28 days before study Day 1
* Immunization with live vaccine or immunoglobulin (Ig) treatment within 28 days before study Day 1 or need for such treatment during the study (including follow-up)
* Any history or presence of active or latent tuberculosis, major infection requiring hospitalization or intravenous anti-infectives within 28 days before study Day 1
* Other major concurrent illness or organ dysfunction as specified in the protocol
* Serum IgG below 6 gram per liter (g/L)
* Known hypersensitivity to atacicept or to any of the components of the formulated atacicept
* Other protocol-defined exclusion criteria could apply
B: 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.
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: A