Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Condition: Asthma
MeSH terms: Asthma
Intervention: GSK3772847; Placebo
Intervention description: GSK3772847 will be available as 100 mg/vial, white to yellow, uniform lyophilized cake in a 5 milliliter (mL) clear glass vial with closure sealed by red metal and yellow overseal.; Commercially sourced sterile normal saline will be provided as Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized in a 1:1 ratio to receive either 10 mg/kg GSK3772847 or matching placebo intravenously.
Masking: Double (Participant, Investigator)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Asthma Control Questionnaire; Allergic fungal airway disease; Asthma Quality of Life Questionnaire; Holter monitoring; Asthma

Summary:

      This study is multicenter, double-blinded parallel group design, where participants with
      moderate to severe asthma with AFAD will be enrolled. Participants will receive three doses
      of 10 milligrams/kilogram (mg/kg) of GSK3772847 every 4 Weeks versus placebo along with
      standard of care. Participants will be randomized in 1:1 ratio to receive either 10 mg/kg
      GSK3772847 intravenously (IV) or matching placebo IV. Participants will receive study
      treatment on Week 0 (Day 1), Week 4 and Week 8. The total duration of the study will be 28
      Weeks and approximately 46 participants will be randomized.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be at least 18 years of age inclusive, at the time of signing the
             informed consent.

          -  Documented history of physician diagnosed moderate or severe asthma for >=12 months
             based on Guidelines and treated with inhaled corticosteroid (ICS) and long-acting
             beta-2-agonist (LABA) for at least 4 months (>=500 micrograms/day [µg/day])
             fluticasone propionate or equivalent as defined in the guidelines.

          -  Pre-bronchodilator FEV1 35-79% of predicted value for participant inclusive

          -  FeNO >= 25 parts per billion (ppb) at Screening

          -  ACQ-5 score >= 1.5 at Screening

          -  Blood eosinophil >=300 cells/microliter at Screening

          -  Evidence of allergic fungal airway disease like Fungal sensitization to any of the
             fungi Aspergillus fumigatus, Penicillium chrysogenum (notatum) at screening measured
             by serum-specific Immunoglobulin (Ig) E test. A history of exacerbations with at least
             1 severe exacerbation (defined as requiring a minimum of 3 days of high-dose oral
             corticosteroids for asthma symptoms) in the previous 12 months.

          -  Body weight within 50-150 kilogram (kg)

          -  Both male and female gender. A female participant is eligible to participate if she is
             not pregnant not breastfeeding, Not a woman of childbearing potential (WOCBP) or A
             WOCBP who agrees to follow the contraceptive guidance during the treatment period and
             for at least 16 weeks after the last dose of study treatment.

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  Historical diagnosis of cystic fibrosis

          -  Concurrent respiratory diseases: Presence of a known pre-existing, clinically
             important respiratory conditions (example 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 or AFAD

          -  Has a history of chronic or recurrent non-pulmonary infectious disease or ongoing
             non-pulmonary 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 IV antibiotics for an infection, within 8 weeks
             prior to the first administration of study drug.

          -  Evidence of poorly controlled chronic medical conditions other than asthma, example,
             participants with known, pre-existing, clinically significant endocrine, autoimmune,
             metabolic, neurological, renal, cardiovascular, gastrointestinal, hepatic, and
             hematological or any other system abnormalities that are uncontrolled with standard
             treatment.

          -  Cardiovascular disease: Clinically significant organic heart disease

          -  Participants with a diagnosis of malignancy or in the process of investigation for a
             malignancy. Participants with carcinoma that have not been in complete remission for
             at least 5 years. Participants 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 participant has been considered cured by treatment.

          -  Eosinophilic diseases: Other conditions that could lead to elevated eosinophil such as
             hyper-eosinophilic syndromes. Participants with a known, pre-existing parasitic
             infestation within 6 months prior to Screening (Visit 1)

          -  Prohibited medications is not permitted within the defined time intervals prior to
             Screening (Visit 1) and throughout the study.

          -  Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test
             result at screening or within 3 months prior to first dose of study treatment.

          -  A known immunodeficiency such as human immunodeficiency virus infection.

          -  Hypersensitivity: significant allergies to humanized monoclonal antibodies or biologic
             or to any components of the formulation used in this study

          -  Clinically significant multiple or severe drug allergies, intolerance to topical
             corticosteroids, or severe post-treatment hypersensitivity reactions (including, but
             not limited to, erythema multiforme major, linear Ig A dermatosis, toxic epidermal
             necrolysis, and exfoliative dermatitis).

          -  Clinically significant abnormality on 12-lead ECG assessment at screening (Visit 1).
             Site investigators will be provided with ECG over-read conducted by a centralized
             independent cardiologist, to assist in evaluation of participant eligibility.

          -  Sinus bradycardia <45 beats per minute (bpm), sinus tachycardia >= 110 bpm, multifocal
             atrial tachycardia (wandering atrial pacemaker with rate >100bpm), evidence of Mobitz
             II second degree or third degree atrioventricular (AV) block, pathological Q waves
             (defined as wide [>0.04 seconds] and deep [>0.4 millivolts (mV) (4 millimeter [mm]
             with 10mm/mV setting)] or >25% of the height of the corresponding R wave, providing
             the R wave was >0.5mV [5mm with 10mm/mV setting], appearing in at least two contiguous
             leads, evidence of ventricular ectopic couplets, bigeminy, trigeminy or multifocal
             premature ventricular complexes, for participants without complete right bundle branch
             block: QTc for heart rate by Fridericia's formula QTc(F) >= 450 millisecond (msec) or
             an ECG that is unsuitable for QT measurements, for participants with complete right
             bundle branch block: QTc(F) >=480 msec or an ECG that is unsuitable for QT
             measurements, ST-T wave abnormalities, clinically significant conduction abnormalities
             and clinically significant arrhythmias.

          -  Smoking history: current smokers or former smokers with a smoking history >= 10 pack
             years

          -  History of alcohol or illegal substance abuse within 2 years prior to Screening
             (Visit1).

          -  Participants at risk of non-compliance, or unable to comply with the study procedures.
             Participants who are unable to follow study instructions such as visit schedule and
             paper diary completion. Participants 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.