Efficacy and Safety Study of GSK3772847 in Subjects With Moderately Severe Asthma



Status:Active, not recruiting
Conditions:Asthma
Therapuetic Areas:Pulmonary / Respiratory Diseases
Healthy:No
Age Range:18 - Any
Updated:3/29/2019
Start Date:September 14, 2017
End Date:May 23, 2019

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A Randomized, Double-blind, Parallel Group, Multicenter, Stratified Study Evaluating the Efficacy and Safety of Repeat Doses of GSK3772847 Compared With Placebo in Participants With Moderately Severe Asthma

GSK3772847, an anti-interleukin (IL)33 receptor monoclonal antibody, is a novel treatment for
asthma. This is a phase 2a study which aims to evaluate efficacy, safety, tolerability,
pharmacokinetic (PK) and pharmacodynamic (PD) profiles of GSK3772847 in subjects with
moderately severe asthma. The study will be conducted in 4 phases including screening, run-in
phase, treatment phase and follow-up. In treatment phase, eligible subjects will be
randomized to receive either GSK3772847 or placebo administered via intravenous (IV) route
every 4 weeks in addition to open-label background therapy of fluticasone propionate/
salmeterol (FP/Sal) 500/50 micrograms (mcg) twice daily. During the treatment phase, the
background therapy will be switched to FP 500 mcg for 2 weeks and the dose of FP will be
reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation. The
total duration of study will be approximately 33 weeks and approximately 148 subjects with
moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/
Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.


Inclusion Criteria:

- Age: At least 18 years of age at the time of signing the informed consent.

- Males and females: A female subject is eligible to participate if she is not pregnant,
not breastfeeding, and at least one of the following conditions applies: Not a woman
of childbearing potential (WOCBP) OR A WOCBP who agrees to follow highly effective
contraceptive methods from 4 weeks prior to the first dose of study medication and
until at least 16 weeks after the last dose of study medication and completion of the
follow-up visit.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and in this protocol.

- A subject with a documented diagnosis of moderate severe asthma based on Global
Initiative for Asthma (GINA) 2016 Guidelines, whose asthma has been managed with
regular treatment of high dose ICS defined as FP 500 mcg twice daily (i.e. 1000 mcg
total daily dose) or equivalent, and LABA for at least 4 months. Additional therapy
with a leukotriene receptor antagonist (LTRA) is permissible.

- Airway reversibility of at least 12 percent and 200 milliliter (mL) in FEV1 at
Screening (Visit 1), or documented reversibility prior to Screening (Visit 1), or
documented history of bronchial hyper reactivity (e.g. fall in FEV1 from baseline of
more than or equal to 20percent with standard doses of methacholine or histamine, or
more than or equal to 15 percent with standardized hyperventilation, hypertonic saline
or mannitol challenge) from a bronchoprovocation study [e.g. methacholine challenge
prior to Screening (Visit 1)].

- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Screening (Visit 1).

- Had at least one asthma exacerbation within 12 months prior to screening that required
treatment with systemic corticosteroid and/or hospitalization.

- All subjects must be able to replace their current Short-Acting Beta2-Agonists (SABA)
treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, per
product label, for the duration of the study.

Randomization inclusion criteria:

- ACQ-5 score more than or equal to 1.0 and less than 4.0 at Visit 2.

- Compliance with completion of the Daily eDiary reporting defined as completion of all
questions/assessments on more than or equal to 4 of the last 7 days during the run-in
period.

Exclusion Criteria:

- Current smokers or former smokers with a smoking history more than or equal to 10 pack
years.

- Presence of a known pre-existing, clinically important respiratory conditions (e.g.
pneumonia, pneumothorax, atelectasis segmental or larger, pulmonary fibrotic disease,
bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive
pulmonary disease, or other respiratory abnormalities) other than asthma.

- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Screening
(Visit 1).

- Subjects with a diagnosis of malignancy or in the process of investigation for a
malignancy. Subjects with carcinoma that have not been in complete remission for at
least 5 years. Subjects who have had carcinoma in situ of the cervix, squamous cell
carcinoma and basal cell carcinoma of the skin would not be excluded based on the 5
year waiting period if the subject has been considered cured by treatment.

- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
result at Screening (Visit 1) or within 3 months prior to first dose of study
treatment.

- Site investigators will be provided with ECG over-read conducted by a centralized
independent cardiologist, to assist in evaluation of subject eligibility.

- Weight: less than 50 kilograms (kg) and more than 150 kg.

- Regular use of systemic corticosteroids for conditions including asthma within 3
months prior to Screening (Visit 1).

- Subjects with high parasympathetic tone (e.g. trained athletes with baseline
bradycardia) or chronic conditions associated with parasympathetic surges (e.g.
migraines).

- Other conditions that could lead to elevated eosinophils such as hypereosinophilic
syndromes. Subjects with a known, pre-existing parasitic infestation within 6 months
prior to Screening (Visit 1).

- Clinically significant organic heart disease [e.g. Coronary artery disease (CAD), New
York Heart Association (NYHA) Class III/IV heart failure].

- Ongoing infections (i.e. not resolved within 7 days prior to Screening [Visit 1]) or
recurrent infections (i.e. requiring treatment for an identical diagnosis within 3
months) requiring systemic antibiotics Known, pre-existing parasitic infestations
within 6 months prior to Screening.

- A subject must not have any clinically significant, uncontrolled condition, or disease
state that, in the opinion of the investigator, would put the safety of the subject at
risk through study participation or would confound the interpretation of the efficacy
results if the condition/disease exacerbated during the study.

- A known immunodeficiency such as human immunodeficiency virus infection.

- Subjects with allergy or intolerance to a monoclonal antibody or biologic or to any
components of the formulation used in this study.

- Subjects with a history (or suspected history) of alcohol misuse or substance abuse
within 2 years prior to Screening (Visit 1).

- Subjects who are unable to follow study instructions such as visit schedule, dosing
directions, study eDiary completion, or use of a standard metered dose inhaler.
Subjects who have known evidence of lack of adherence to controller medication and/or
ability to follow physician's recommendations. Any infirmity, disability, or
geographic location that would limit compliance for scheduled visits.

- Subjects who have previously participated in a study of GSK3772847.

- Use of the prohibited medications is not permitted within the defined time intervals
prior to Screening (Visit 1) and throughout the study. Potential subjects should not
be washed out of their medication solely for the purpose on enrolling in the trial.

- A subject will not be eligible for this study if he/she is an immediate family member
of the participating investigator, sub investigator, study coordinator, or employee of
the participating investigator.

- In the opinion of the investigator, any subject who is unable to read and/or would not
be able to complete a diary card/questionnaire.

- Subjects with a history of psychiatric disease, intellectual deficiency, poor
motivation or other conditions that will limit the validity of informed consent to
participate in the study.

Randomization exclusion criteria:

- Evidence of clinically significant abnormal laboratory tests during screening which
are still abnormal upon repeat analysis and are not believed to be due to disease(s)
present. Each Investigator will use his/her own discretion in determining the clinical
significance of the abnormality.

- Evidence of clinically significant abnormal ECG findings at Visit 2.

- An abnormal and significant finding from 24-hour Holter monitoring at Screening (Visit
1). Investigators will be provided with Holter reviews conducted by an independent
cardiologist to assist in evaluation of subject eligibility.

- Liver function at screening (Visit 1): ALT more than 2 x upper limit of normal (ULN)
and bilirubin more than 1.5xULN (isolated bilirubin more than 1.5xULN is acceptable if
bilirubin is fractionated and direct bilirubin less than 35 percent); Current or
chronic history of liver disease, or known hepatic or biliary abnormalities (with the
exception of Gilbert's syndrome or asymptomatic gallstones).

- Subjects with ongoing asthma exacerbation at the time of Visit 2.

- A pre-bronchodilator FEV1 less than 50 percent predicted of normal value at Visit 2.

- Positive pregnancy test at Visit 0, Screening (Visit 1) or Visit 2.

- Ongoing or recurrent infections requiring systemic antibiotics.
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Scottsboro, Alabama 35768
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