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

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ClinicalTrials.gov Identifier: NCT03393806
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 3, 2018
First Posted Date  ICMJE January 9, 2018
Last Update Posted Date June 13, 2019
Actual Study Start Date  ICMJE April 18, 2018
Estimated Primary Completion Date October 17, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Change from Baseline in blood eosinophils [ Time Frame: Baseline and up to Day 88 ]
    Blood samples will be collected at indicated time points for the assessment of eosinophil
  • Change from Baseline in fractional exhaled nitric oxide (FeNO) [ Time Frame: Baseline and up to Day 88 ]
    FeNO will be measured using a handheld electronic device
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03393806 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2018)
  • Serum concentrations of GSK3772847 [ Time Frame: 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 ]
    Blood samples will be collected at indicated time points for assessment of serum concentrations
  • Serum levels of free soluble suppressor of tumorigenicity 2 (ST2) [ Time Frame: Day 1 Pre and post-dose; Day 15; Day 29 Post dose; Day 57 pre and post dose; Day 85, Day 169 ]
    Blood samples will be collected at indicated time points to measure free soluble ST2
  • Serum levels of total soluble ST2 [ Time Frame: Day 1 Pre and post-dose; Day 15; Day 29 Post dose; Day 57 pre and post dose; Day 85, Day 169 ]
    Blood samples will be collected at indicated time points to measure total soluble ST2
  • Number of participants with positive result of serum anti-GSK3772847 antibodies post dosing [ Time Frame: Up to Day 172 ]
    Blood samples will be collected at indicated time points and anti-GSK3772847 antibodies will be assessed using a tiered approach.
  • Titers of serum anti-GSK3772847 antibodies post dosing [ Time Frame: Up to Day 172 ]
    Blood samples will be collected at indicated time points and anti-GSK3772847 antibodies will be assessed using a tiered approach.
  • Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) absolute score at Weeks 2, 4, 8 and 12 [ Time Frame: Baseline and at Weeks 2, 4, 8 and 12 ]
    ACQ-5 is a 5-item questionnaire that is a measure of the participant's asthma control. The five questions include about the frequency and/or severity of symptoms like nocturnal awakening, activity limitation, shortness of breath and wheeze. The score scales from zero (totally controlled) and 6 (severely uncontrolled)
  • Change from Baseline in Asthma Quality of Life Questionnaire (AQLQ) total and domain scores at Weeks 2, 4, 8 and 12 [ Time Frame: Baseline and at Weeks 2, 4, 8 and 12 ]
    AQLQ is 32 items four domains questionnaire used for evaluation of impact of asthma treatments on the quality of life of participants. The scores are evaluated from 1 (total impairment) and 7 (no impairment)
  • Number of responders to ACQ-5 [ Time Frame: Up to Day 88 ]
    ACQ-5 is a 5 question tool used to measure attributes of asthma control and the score ranges from 0 to 6 where 0 is no impairment/limitation and 6 is total impairment/limitation. A responder to ACQ-5 will be defined as a participant who has a decrease from Baseline in ACQ-5 score of 0.5 or more.
  • Number of responders to AQLQ [ Time Frame: Up to Day 88 ]
    AQLQ is a 32 items four domain questionnaire used to measure quality of life participants due to asthma treatment and the scores ranges from 1 to 7 where 1 indicates total impairment and 7 indicates no impairment. A responder to AQLQ will be defined as a participant who has an increase from Baseline in AQLQ score of 0.5 or more.
  • Change from Baseline in forced expiratory volume in 1 second (FEV1) [ Time Frame: Up to Day 88 ]
    Spirometry assessment will include pre-bronchodilator FEV1
  • Change from Baseline in forced vital capacity (FVC) [ Time Frame: Up to Day 88 ]
    Spirometry assessment will include pre-bronchodilator FVC
  • Number of participants with treatment emergent adverse events (AE) and serious AEs (SAE) [ Time Frame: Up to Day 172 ]
    An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
  • Number of participants with abnormal hematology parameters [ Time Frame: Up to Day 172 ]
    Laboratory assessment for hematology parameters will include Platelet count, hemoglobin, Red blood cell (RBC) count, hematocrit, Red blood cell distribution width (RDW), RBC indices like mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). White blood cell (WBC) count with differential will include neutrophils, lymphocytes, monocytes, eosinophils and basophils.
  • Number of participants with abnormal clinical chemistry parameters [ Time Frame: Up to Day 172 ]
    Laboratory assessment for clinical chemistry parameters will include blood urea nitrogen (BUN), potassium, calcium, sodium, creatinine, non-fasting glucose, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline phosphate, Gamma-glutamyl transferase (GGT), albumin, phosphorus, carbon dioxide, total protein, creatine phosphokinase (CPK), total and direct bilirubin
  • Number of participants with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Up to Day 172 ]
    Blood pressure will be measured in supine position after 5 minutes rest
  • Number of participants with abnormal heart rate [ Time Frame: Up to Day 172 ]
    Heart rate will be measured in supine position after 5 minutes rest
  • Number of participants with abnormal findings in Electrocardiogram (ECG) [ Time Frame: Up to Day 88 ]
    Single 12-lead ECG will be obtained using an ECG machine that automatically measures heart rate, PR, QRS, QT, and QT interval corrected for heart rate (QTc) and ventricular rate
  • Number of participants with abnormal 24-hour Holter findings [ Time Frame: Day 1 ]
    Holter assessment will be used for quantitative assessment of abnormal rhythm events. Holter monitor will be placed 30-60 minutes prior to dosing.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Repeat Dose Study of GSK3772847 in Participants With Moderate to Severe Asthma With Allergic Fungal Airway Disease (AFAD)
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: 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.
  • Drug: Placebo
    Commercially sourced sterile normal saline will be provided as Placebo
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: GSK3772847
  • Placebo Comparator: Participants receiving placebo
    Participants will be randomized to receive matching placebo as IV infusion
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 3, 2018)
46
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 9, 2020
Estimated Primary Completion Date October 17, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE France,   Netherlands,   Russian Federation,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03393806
Other Study ID Numbers  ICMJE 207972
2017-003544-20 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP