Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Double-blind, Placebo-controlled, Multiple Intravenous, Ascending-Dose Study of CNTO 136 to Evaluate Safety and Pharmacokinetics in Subjects With Cutaneous Lupus Erythematosus and to Evaluate Safety and Pharmacokinetics in a Cohort of Subjects With Systemic Lupus Erythematosus
Brief Summary: The main purpose of this study was to evaluate the safety and pharmacokinetics (PK, the action of a drug in the body over a period of time) of multiple intravenous (IV) administrations of CNTO 136 in patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). The secondary goal of this study was to assess the pharmacodynamics (biochemical and physiological effects of a drug and the mechanisms of action), immune response, and clinical response.


Options:
A: Inclusion Criteria:

* Patients must meet all of the following criteria:
* Adult males and females ≥ 18 years at the time of the first dose of study drug.
* Written informed consent obtained from the patient/patient's legal guardian
* Diagnosis of SLE: Patients must have previously met ≥ 4 of the 11 revised ACR criteria
* Current background treatments may include the following medications prior to randomization: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and antimalarials, such as hydroxychloroquine ≤ 600 mg/day, and prednisone ≤ 20 mg daily (or an equivalent dose of another oral corticosteroid) for at least 28 days
* Sexually active females, unless surgically sterile or at least two years post-menopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, 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 28 days before the first dose of study drug, and must agree to continue using such precautions through the study period of 84 days. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions through Study Day 84.
* Ability to complete follow-up period of 84 days as required by the protocol.

Exclusion Criteria:

* Weight ≥ 120 kg
* Use of cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil or cyclosporine within 28 days before study entry
* Use of doses of corticosteroids higher than the equivalent of prednisone 20 mg/day (or an equivalent dose of another corticosteroid) within 28 days before study entry
* In the opinion of the investigator, a likelihood of requiring initiation of immunosuppressant therapy (e.g., prednisone \>20 mg daily (or an equivalent dose of another oral corticosteroid), azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, or dapsone) within the 28 days after study entry. Antimalarial dosing must be held constant during the study, but analgesics and NSAIDs may be varied.
* Current treatment with coumadin
* Treatment with immunoglobulin or blood products within 28 days before entry into the study
* Treatment with any investigational drug therapy within 28 days before entry into the study; in the case of cell-depleting therapies, such as B or T cell depletion, cell counts that remain below acceptable or baseline levels (use of licensed agents for indications not listed in the package insert is permitted)
* History of primary immunodeficiency
* History of allergic reactions likely to be exacerbated by any component of the study drug
* Previous medical history, or evidence, of an intercurrent illness, other than SLE, that may compromise the safety of the patient in the study
* Clinically significant cardiac disease, including: unstable angina; myocardial infarction within 6 months; congestive heart failure; arrhythmia requiring active therapy, with the exception of clinically insignificant extra systoles, or minor conduction abnormalities; and history of clinically significant abnormality on electrocardiogram
* Evidence of significant active infection, or vaccination with live attenuated viruses, currently or in the 2 weeks before randomization
* Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening
* A history of severe infection with viruses of the herpes family including Epstein-Barr virus requiring hospitalization, disseminated herpes, herpes encephalitis, ophthalmic herpes, or cytomegalovirus
* Herpes zoster ≤ 3 months prior to screening
* Current suppressive antiviral therapy for herpes or other viral infections
* Ongoing, chronic infectious disease such as chronic renal infection or chronic chest infection with bronchiectasis or sinusitis
* Pregnancy (females, unless surgically sterile or at least two years post-menopausal must have a negative serum pregnancy test within 14 days before receiving the study drug and a negative urine pregnancy test on Study Day 0 before receiving the study drug)
* Nursing mother
* History of alcohol or drug abuse within the past 2 years
* Presence of end-stage renal disease, or rapidly progressive glomerulonephritis
* Active central nervous system lupus
* History of stroke, or any cerebrovascular disease requiring medication/treatment.
* History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \>1 year prior to enrollment
* At screening (must be within14 days before entry into the study) any of the following:

  * AST \> 1.5x upper limit of normal range (ULN)
  * ALT \> 1.5x ULN
  * creatinine \> 1.5x ULN for patient's age, sex and weight
  * serum K above or below the normal range
  * hemoglobin \< 8 g/dL
  * white blood cell count \< 1,800/mm3 (Superscript)
  * neutrophils \< 1,500/mm3 (Superscript)
  * platelet count \< 50,000/mm3 (Superscript)
  * other abnormal laboratory values in the screening panel that in the opinion of the principal investigator are judged to potentially confound analysis of study results
B: Inclusion Criteria:

* Diagnosis of SLE by American College of Rheumatology guidelines.
* On stable SLE treatment
* Active SLE disease
* Serologically active
* 18 years of age or older
* Receiving stable doses of prednisone between 7.5 mg and 40 mg per day

Exclusion Criteria:

* Severe active vasculitis, active central nervous system lupus, active lupus nephritis, uncontrolled hypertension, or uncontrolled diabetes.
* Known to be positive for HIV and/or positive at the screening visit for hepatitis B, or hepatitis C.
* Liver disease.
* Anemia, neutropenia, or thrombocytopenia.
* Malignancy within past 5 years
* Active infection requiring hospitalization or treatment with parenteral antibiotics within the past 60 days or history of repeated herpetic viral infections.
* History of active tuberculosis or a history of tuberculosis infection.
* Participation in the active treatment arm of any Phase 2 or Phase 3 clinical trial for a molecule that primarily targets the B cell pathway in the past 18 months.
* Prior administration of any B cell depleting therapy in the past 18 months.
* Pregnant or nursing
* History of congenital immunodeficiency
C: Inclusion Criteria:

* Diagnosis of cutaneous lupus erythematosus (CLE, including subacute cutaneous lupus erythematosus, discoid lupus erythematosus, or lupus erythematosus tumidus) or systemic lupus erythematosus (SLE)

  * Had a body weight less than or equal to 100 kg
  * Patients in Part A who were taking systemic medications for CLE had to be on a stable dose for 4 weeks before the first study agent infusion
  * Patients in Part B taking systemic medications for SLE had to be on a stable dose for at least 3 months before the first study agent infusion
  * Given informed consent and willing and able to adhere to the study visit schedule and other protocol requirements; agreed to avoid alcohol intake; and took adequate measures to prevent pregnancy

Exclusion Criteria:

* Significant history of or concurrent medical condition (other than lupus)
* Use of specific previous or concurrent medications or investigational therapies
* Known or suspected allergy to the study agent or it constituents, having recently donated blood, or having any significant laboratory test values requiring intervention
* Patients with SLE in Part B could not have active central nervous system lupus
D: Inclusion criteria :

* Patients diagnosed as cutaneous lupus erythematosus (CLE)

Exclusion criteria:

* Patients receiving corticosteroid more than 15mg/day of the equivalent dose of prednisolone.
* Patients whose CLASI activity scores were less than 4 point at the initiation of Screening (Visit 1) and Day1 (Visit 2) (evaluated by a dermatology specialist).
* Patients whose fluctuations of CLASI activity scores were ≥20% between Visit 1 and Visit 2 (evaluated by a dermatology specialist). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Answer: C