A Phase 2a Study to Evaluate the Effects of Sirukumab in Subjects With Severe Poorly Controlled Asthma

Exclusion Criteria

• •Presence of a known pre-existing, clinically important lung condition other than asthma. This includes chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or a history of lung cancer.
• •Lower respiratory tract infection (LRTI) or asthma exacerbation requiring antibiotics or systemic corticosteroids within 6 weeks of screening.
• •Evidence of respiratory infection at screening.
• •Has a history of chronic or recurrent infectious disease or ongoing infection including, but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (example, recurrent pyelonephritis, chronic non-remitting cystitis), or open, draining skin wound or an ulcer.
• •Serious infection within 8 weeks of enrolment, including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis; or has been hospitalized for an infection; or has been treated with intravenous (IV) antibiotics for an infection, within 8 weeks prior to the first administration of study drug.
• •Opportunistic infection, example, a nontuberculous mycobacterial infection or cytomegalovirus, pneumocystosis, aspergillosis within 6 months prior to screening.
• •Evidence of poorly controlled chronic medical conditions other than asthma, example, subjects with known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, and haematological or any other system abnormalities that are uncontrolled with standard treatment.
• •Current history of suicidal ideation or a past history of suicide attempt.
• •Lactating, pregnant, or planning to become pregnant during the study.
• •Malignancy within 5 years (except local basal cell carcinoma, or fully excised local dermal, squamous cell carcinoma).
• •Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis.
• •Has a history of gastrointestinal perforation or currently has active diverticulitis.
• •QTcorrected (QTc) \>450 milliseconds (msec) or QTc \>480 msec in subjects with Bundle Branch Block. Notes: The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read; The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
• •Alanine transaminase (ALT) \>1.5 times upper limit of normal (ULN) and bilirubin \>ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• •Laboratory abnormalities: Neutrophils \<1.95 multiplied by 10 raise to 9 per liter; Platelet count \<140 multiplied by 10 raise to 9 per liter; Hemoglobin \<8.5 grams per decilitre (g/dL); WBC count \<3.5 × multiplied by 10 raise to 9 per liter.
• •Use of systemic corticosteroids within 6 weeks of screening. The only exception is subjects who take \<=10 mg prednisolone (or equivalent) orally per day for chronic maintenance therapy, and who have been maintained on this regimen for \>=12 weeks.
• •The subject has received an investigational drug within 30 days or 5-half-lives (whichever is longer) prior to the first dose of study drug.
• •Use of other monoclonal antibodies within 3 months (or 130 days in the case of Xolair) of screening.
• •Live virus or bacterial vaccine from 30 days before screening.
• •Immunomodulatory/suppressive agents including but not limited to cyclophosphamide, a cytotoxic agent, cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 3 months of screening.
• •Bronchial thermoplasty within 12 months of screening.
• •Subjects with a smoking history of \>=10 pack years (pack years = number of cigarettes smoked per day divided by 20 into number of years smoked). Note: Subjects who are current smokers, or ex-smokers (having given up smoking for \>=6 months), are eligible for the study if their smoking history is \<10 pack years.
• •History of alcohol or illegal substance abuse consumption within 2 years of the study start.
• •History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (example, compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments.
• •Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
• •Chest X-Ray (CXR) within 6 months of screening showing evidence of active or inactive tuberculosis (TB), or other clinically significant disease other than asthma. If a CXR is not available, it must be performed at screening.
• •Positive for Mycobacterium tuberculosis using QuantiFERON Gold test at screening.
• •Human Immunodeficiency Virus (HIV) positive or determined to be HIV positive at screening, testing to be conducted in accordance with local practice.
• •Presence of hepatitis B surface antigen (HBsAg) or core antigen (HBcAg). Subjects who are HBsAg negative, but hepatitis core antigen positive may be included if they are polymerase chain reaction (PCR) negative for Hepatitis B deoxyribonucleic acid (DNA).
• •Positive hepatitis C (Hep C) test result at screening or within 3 months prior to first dose of study treatment.