Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)

NCT ID: NCT03393806

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-18
• Study Completion Date: 2020-01-06

Brief 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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Participants receiving GSK3772847

Participants will be randomized to receive GSK3772847 as IV infusion. Participants will receive three doses ( Day 1, Day 29 and Day 57) of GSK3772847 every 4 weeks

Group Type: EXPERIMENTAL

GSK3772847

Intervention Type: DRUG

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.

Participants receiving placebo

Participants will be randomized to receive matching placebo as IV infusion

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Commercially sourced sterile normal saline will be provided as Placebo

Interventions

GSK3772847

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.

Intervention Type: DRUG

Placebo

Commercially sourced sterile normal saline will be provided as Placebo

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Brest, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Izhevsk, , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Ulyanovsk, , Russia

GSK Investigational Site

Wythenshawe, Greater Manchester, United Kingdom

GSK Investigational Site

Leicester, Leicestershire, United Kingdom

GSK Investigational Site

Liverpool, Merseyside, United Kingdom

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Bradford, , United Kingdom

GSK Investigational Site

Edgbaston, , United Kingdom

Countries

France; Netherlands; Russia; United Kingdom

References

Akinseye C, Crim C, Newlands A, Fairman D. Efficacy and safety of GSK3772847 in participants with moderate-to-severe asthma with allergic fungal airway disease: A phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial. PLoS One. 2023 Feb 3;18(2):e0281205. doi: 10.1371/journal.pone.0281205. eCollection 2023.

Reference Type: DERIVED

PMID: 36735745 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-003544-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207972

Identifier Type: -

Identifier Source: org_study_id