Last updated: 07/17/2024 17:35:28
Repeat dose study of GSK3772847 in participants with moderate to severe asthma with allergic fungal airway disease (AFAD)
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A double blind (sponsor open) placebo-controlled, stratified, parallel group study to evaluate the efficacy and safety of repeat doses of GSK3772847 in participants with moderate to severe asthma with allergic fungal airway disease (AFAD)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Change from Baseline in blood eosinophils
Timeframe: Baseline and up to Day 88
Change from Baseline in fractional exhaled nitric oxide (FeNO)
Timeframe: Baseline and up to Day 88
Secondary outcomes:
Serum concentrations of GSK3772847
Timeframe: Day 1 post-end of infusion, Day 15, Pre-dose on Day 29, Pre-dose and post-dose on Day 57, Day 85 and Day 169
Serum levels of free soluble suppressor of tumorigenicity 2 (ST2)
Timeframe: Day 1 Pre and post-dose; Day 15; Day 29 Post dose; Day 57 pre and post dose; Day 85, Day 169
Serum levels of total soluble ST2
Timeframe: Day 1 Pre and post-dose; Day 15; Day 29 Post dose; Day 57 pre and post dose; Day 85, Day 169
Number of participants with positive result of serum anti-GSK3772847 antibodies post dosing
Timeframe: Up to Day 172
Titers of serum anti-GSK3772847 antibodies post dosing
Timeframe: Up to Day 172
Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) absolute score at Weeks 2, 4, 8 and 12
Timeframe: Baseline and at Weeks 2, 4, 8 and 12
Change from Baseline in Asthma Quality of Life Questionnaire (AQLQ) total and domain scores at Weeks 2, 4, 8 and 12
Timeframe: Baseline and at Weeks 2, 4, 8 and 12
Number of responders to ACQ-5
Timeframe: Up to Day 88
Number of responders to AQLQ
Timeframe: Up to Day 88
Change from Baseline in forced expiratory volume in 1 second (FEV1)
Timeframe: Up to Day 88
Change from Baseline in forced vital capacity (FVC)
Timeframe: Up to Day 88
Number of participants with treatment emergent adverse events (AE) and serious AEs (SAE)
Timeframe: Up to Day 172
Number of participants with abnormal hematology parameters
Timeframe: Up to Day 172
Number of participants with abnormal clinical chemistry parameters
Timeframe: Up to Day 172
Number of participants with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Up to Day 172
Number of participants with abnormal heart rate
Timeframe: Up to Day 172
Number of participants with abnormal findings in Electrocardiogram (ECG)
Timeframe: Up to Day 88
Number of participants with abnormal 24-hour Holter findings
Timeframe: Day 1
Interventions:
Enrollment:
17
Primary completion date:
2019-09-10
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Chika Akinseye, Courtney Crim, Amy Newlands, David Fairman. 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;18(2):e0281205
DOI: https://doi.org/10.1371/journal.pone.0281205
PMID: 36735745
Medical condition
Asthma
Product
GSK3772847
Collaborators
Not applicable
Study date(s)
April 2018 to January 2020
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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
Inclusion and exclusion 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.
Trial location(s)
Showing 1 - 6 of 18 Results
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2019-09-10
Actual study completion date
2020-06-01
Plain language summaries
Summary of results in plain language
Available language(s): Dutch, English, French, Russian
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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