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

Inclusion Criteria:

- Subjects aged 18 - 75 years, inclusive.

- Severe, uncontrolled asthma according to the following criteria: Physician-diagnosed
asthma for >=12 months, and; treatment for at least 3 months with >=880 microgram per
day of fluticasone propionate (FP) dry powder for inhalation (DPI) or its equivalent,
plus a long acting beta agonist (LABA), and' ACQ-7 score >=1.5, and; a documented
history (e.g., medical record verification) in the 12 months prior to Visit 2 of >=1
exacerbation resulting in prescription for systemic oral corticosteroids or
hospitalisation or extended observation in a hospital emergency room or outpatient
centre. [For subjects on maintenance systemic corticosteroids, at least double the
existing maintenance dose for at least 3 days is required] and; pre-bronchodilator
FEV1 35-80% inclusive, with evidence of >=12% (and 200 milliliter [mL]) reversibility
in FEV1 measured 15-30 minutes following 4 actuations of salbutamol (100 microgram per
actuation) or albuterol (90 microgram per actuation) via pre-metered dose inhaler
(pMDI). This reversibility criterion should have been documented in the 12-months
prior to Screening. If no prior data are available this should be demonstrated either
at Screening (Visit 2) or at the Randomization visit (Visit 3); blood eosinophil count
<300 cells per microliter at screening.

- Body mass index 18-45 kilogram per meter square.

- Male or Females and Male subjects with female partners of child bearing potential must
comply with the following contraception requirements from the time of first dose of
study medication until a cycle of spermatogenesis following five terminal half- lives
after the last dose of study medication: Vasectomy with documentation of azoospermia;
Male condom plus partner use of one of the following contraceptive options:
Contraceptive subdermal implant; Intrauterine device or intrauterine system; Combined
estrogen and progestogen oral contraceptive; Injectable progesterone; Contraceptive
vaginal ring; Percutaneous contraceptive patches.

- This is an all-inclusive list of those methods that meet the following GlaxoSmithKline
(GSK) definition of highly effective: having a failure rate of less than 1% per year
when used consistently and correctly and, when applicable, in accordance with the
product label. For non-product methods (e.g., male sterility), the investigator
determines what is consistent and correct use. The GSK definition is based on the
definition provided by The International Council for Harmonization of Technical
Requirements for Pharmaceuticals for Human Use (ICH).

- The investigator is responsible for ensuring that subjects understand how to properly
use these methods of contraception.

- A female subject is eligible to participate if she is of non-child bearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as age greater than 60 or 12 months of spontaneous amenorrhea
with an appropriate clinical profile [in questionable cases a blood sample with
simultaneous follicle stimulating hormone (FSH) >40 milliinternational units per
milliliter (MlU/mL) and estradiol <40 picogram per milliliter (pg/mL) (<140 picomole
per liter [pmol/L] is confirmatory) or if of child-bearing potential is using a highly
effective method for avoidance of pregnancy for the duration of dosing and until 4
months post last-dose.

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

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.