AzTrials
AzTrials

AsthmaPhase 2NCT03207243

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

A Phase 2 study testing GSK3772847, Fluticasone propionate/salmeterol and Fluticasone propionate in people with Asthma, run by GlaxoSmithKline at 64 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Asthma
What is being tested?
GSK3772847, Fluticasone propionate/salmeterol and Fluticasone propionate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
165 participants
Where
64 sitesin 6 countries
Study dates
14 Sep 2017to 15 May 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 11Show fewer
  • 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.

Who cannot join

  • 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.
Show all 31Show fewer
  • 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.

Trial locations and contacts

64 sites in 6 countries.

64 sites in 6 countries

United States33 sites

  • GSK Investigational Site

    Adairsville, Georgia, 30103

  • GSK Investigational Site

    Ann Arbor, Michigan, 48109-5360

  • GSK Investigational Site

    Bakersfield, California, 93301

  • GSK Investigational Site

    Baltimore, Maryland, 21224

  • GSK Investigational Site

    Birmingham, Alabama, 35209

  • GSK Investigational Site

    Boerne, Texas, 78006

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599-7248

  • GSK Investigational Site

    Charlotte, North Carolina, 28277

  • GSK Investigational Site

    Cincinnati, Ohio, 45231

  • GSK Investigational Site

    Coral Gables, Florida, 33134

  • GSK Investigational Site

    Hialeah, Florida, 33012

  • GSK Investigational Site

    Long Beach, California, 90806

  • GSK Investigational Site

    Los Angeles, California, 90017

  • GSK Investigational Site

    Madison, Wisconsin, 53792

  • GSK Investigational Site

    Medford, Oregon, 97504

  • GSK Investigational Site

    Miami, Florida, 33134

  • GSK Investigational Site

    Miami, Florida, 33135

  • GSK Investigational Site

    Miami, Florida, 33144

  • GSK Investigational Site

    Miami, Florida, 33174

  • GSK Investigational Site

    Miami, Florida, 33175

  • GSK Investigational Site

    Miami, Florida, 33185

  • GSK Investigational Site

    Miami, Florida, 33186

  • GSK Investigational Site

    Mooresville, North Carolina, 28117

  • GSK Investigational Site

    New Haven, Connecticut, 06510

  • GSK Investigational Site

    Newport Beach, California, 92663

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15213

  • GSK Investigational Site

    Rochester, New York, 14642

  • GSK Investigational Site

    Scottsboro, Alabama, 35768

  • GSK Investigational Site

    St Louis, Missouri, 63108

  • GSK Investigational Site

    Toledo, Ohio, 43617

  • GSK Investigational Site

    Tulsa, Oklahoma, 74136

  • GSK Investigational Site

    Williamsburg, Virginia, 23188

  • GSK Investigational Site

    Winter Park, Florida, 32789

Other trials in United States

Canada9 sites

  • GSK Investigational Site

    Hamilton, Ontario, L8N 3Z5

  • GSK Investigational Site

    Montreal, Quebec, H2X 3E4

  • GSK Investigational Site

    Montreal, Quebec, H4A 3J1

  • GSK Investigational Site

    Ottawa, Ontario, K1G 6C6

  • GSK Investigational Site

    Québec, G1V 4G5

  • GSK Investigational Site

    Sherwood Park, Alberta, T8H 0N2

  • GSK Investigational Site

    Trois-Rivières, Quebec, G8T 7A1

  • GSK Investigational Site

    Vancouver, British Columbia, V5Z 1M9

  • GSK Investigational Site

    Vancouver, British Columbia, V6Z 1Y6

Other trials in Canada

Russia8 sites

  • GSK Investigational Site

    Chelyabinsk, 454106

  • GSK Investigational Site

    Kemerovo, 650000

  • GSK Investigational Site

    Saint Petersburg, 194356

  • GSK Investigational Site

    Saint Petersburg, 195067

  • GSK Investigational Site

    Saint Petersburg, 198328

  • GSK Investigational Site

    Samara, 443068

  • GSK Investigational Site

    Tomsk, 634028

  • GSK Investigational Site

    Ulyanovsk, 432063

Other trials in Russia

Mexico7 sites

  • GSK Investigational Site

    Cuernavaca, Morelos, 62290

  • GSK Investigational Site

    Guadalajara, Jalisco, 44100

  • GSK Investigational Site

    Mérida, Yucatán, 97070

  • GSK Investigational Site

    Mexico City, 03100

  • GSK Investigational Site

    México DF, 14050

  • GSK Investigational Site

    Monterrey, Nuevo León, 64060

  • GSK Investigational Site

    Villahermosa, Tabasco, 86035

Other trials in Mexico

Australia4 sites

  • GSK Investigational Site

    Clayton, Victoria, 3168

  • GSK Investigational Site

    Melbourne, Victoria, 3004

  • GSK Investigational Site

    Parkville, Victoria, 3050

  • GSK Investigational Site

    Woodville South, South Australia, 5011

Other trials in Australia

Ukraine3 sites

  • GSK Investigational Site

    Kyiv, 02002

  • GSK Investigational Site

    Kyiv, 02091

  • GSK Investigational Site

    Kyiv, 03049

Other trials in Ukraine

About this study

Official title: 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 165 subjects with moderately severe asthma who are maintained on high-dose of inhaled corticosteroids/ Long-Acting Beta-2-Agonists (ICS/LABA) will be randomized.

Conditions
Asthma
Being tested
GSK3772847, Placebo, Fluticasone propionate/salmeterol, Fluticasone propionate
Keywords
Severe asthma, Safety, GSK3772847, Efficacy
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3772847Drug

    GSK3772847 10 mg/kg will be administered as IV infusion once every 4 weeks to randomized subjects.

  • PlaceboDrug

    Placebo sterile normal saline will be administered as IV infusion once every 4 weeks to randomized subjects.

  • Fluticasone propionate/salmeterolDrug

    FP/Sal 500/50 mcg will be administered via inhalation route twice daily to all subjects.

  • Fluticasone propionateDrug

    FP 500, 250, 100 or 50 mcg will be administered via inhalation route twice daily to all subjects.

Study groups in NCT03207243
Study groupRoleWhat they receive
Subjects receiving GSK3772847ExperimentalEligible subjects will receive GSK3772847 once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation.
Receives: Drug: GSK3772847; Drug: Fluticasone propionate/salmeterol; Drug: Fluticasone propionate
Subjects receiving placebo drugPlacebo comparatorEligible subjects will receive placebo once every 4 weeks via IV route along with 500/50 mcg FP/Sal twice daily for first 2 weeks and dose of FP was reduced by approximately 50 percent at every 2 weeks until complete FP discontinuation.
Receives: Drug: Placebo; Drug: Fluticasone propionate/salmeterol; Drug: Fluticasone propionate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Loss of Asthma Control Over Weeks 0-16

    Loss of asthma control is defined as: Asthma Control Questionnaire (ACQ-5) score increase from Baseline >=0.5 point or pre-bronchodilator forced expiratory volume in 1 second (FEV1) decrease from baseline >7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral corticosteroid [OCS] and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage of participants experiencing loss of asthma control up to Week 16 has been presented. Modified Intent-to-Treat (Loss of Control) (mITT_LoC) population consisted of all randomized participants who took at least 1 dose of study treatment and if participants experienced loss of asthma control, they were analyzed according to actual treatment at time of loss of control.

    Measured: Up to Week 16

Secondary outcomes (51)

  1. Percentage of Participants With >=0.5 Point Asthma Control Questionnaire (ACQ-5) Score Increase From Baseline

    The ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response options for all these questions range from zero (no impairment/limitation) to six (total impairment/ limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. A change of >=0.5 in score suggests a clinically important change in score. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment

    Measured: Baseline and up to Week 16

  2. Percentage of Participants Who Have Pre-bronchodilator FEV1 Decrease From Baseline >7.5 %

    Pulmonary function is measured by FEV1. FEV1 is the amount of air expired in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. Baseline is defined as the latest available pre-dose assessment (Day 1). Decrease from Baseline >7.5 % in score suggests worsening of condition.

    Measured: Baseline and up to Week 16

  3. Percentage of Participants With Inability to Titrate Inhaled Corticosteroids (ICS)

    Corticosteroid titration allows overall clinical evaluation of the participant's asthma status taking into account both lung function and symptom control. Inability to titrate inhaled corticosteroids indicates loss of asthma control.

    Measured: Up to Week 16

  4. Percentage of Participants With Clinically Significant Asthma Exacerbation

    A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization.

    Measured: Up to Week 16

  5. Percentage of Participants With Loss of Asthma Control Over Weeks 0-6

    Loss of asthma control is defined as: ACQ-5 score increase from Baseline >=0.5 point or pre-bronchodilator FEV1 decrease from Baseline >7.5 % or inability to titrate inhaled corticosteroid or a clinically significant asthma exacerbation (requiring oral OCS and/or hospitalization). The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Baseline is defined as Day1. Percentage of participants experiencing loss of asthma control up to Week 6 has been presented.

    Measured: Up to Week 6

  6. Time to Loss of Asthma Control

    Time to loss of asthma control was analyzed using Kaplan-Meier analysis. In this analysis, participants were either be counted as an event or they were censored. An event is defined as participants who experience loss of asthma control during the study. Censoring is defined as participants who discontinued investigational product for reasons other than loss of asthma control. The analysis shown is for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment. Participants who didn't experience loss of asthma control were also censored at day 113.

    Measured: Up to Week 16

  7. Percentage of Participants With Clinically Significant Asthma Exacerbation or Inability to Titrate

    A clinically significant asthma exacerbation is defined as one requiring oral corticosteroid and/or hospitalization. Participants with clinically significant asthma exacerbation or inability to titrate FP indicated loss of asthma control.

    Measured: Up to Week 16

  8. Number of Participants Experiencing Asthma Related Hospitalization During the Study Period

    Hospitalization is defined as an inpatient stay or least an overnight stay at the hospital or emergency ward for observation or other equivalent facility. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Up to Week 16

  9. Rate Per 1000 Person-years of Participants With Hospitalization

    An event is defined as an on-treatment asthma-related hospitalization or emergency room visit and participants can contribute to more than one event. Rate is calculated as number of events * 1000 divided by (number of participants in treatment group * mean treatment exposure in years). Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Up to Week 16

  10. Number of Hospitalizations or Emergency Room Visits Per Participants

    The number of hospitalization or emergency room visit made by per participant due to loss of asthma control have been presented in category titles. Data has been presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Up to Week 16

  11. Change From Baseline in Asthma Control Questionnaire (ACQ-5) Total Score

    ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath \& wheeze) enquire about the frequency \&/or severity of symptoms over the previous week. The response options range from zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16

  12. Percentage of Participants With <=-0.5 Point ACQ-5 Score Decrease From Baseline (Responder)

    ACQ-5 is a five-item, self-completed questionnaire, which measures asthma control of a participant. The five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath \& wheeze) enquire about the frequency \&/or severity of symptoms over the previous week. The response options range from zero (no impairment/limitation) to six (total impairment/limitation) scale. ACQ-5 score ranges from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicate lower asthma control. Baseline is the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. A responder is defined as participants with change from Baseline of <= -0.5 point at given time point. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and Week 16

  13. Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score

    SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on Health-related quality of life (HRQoL) of participants with Chronic Obstructive Pulmonary Disease (COPD). It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is defined as the latest available assessment prior to first dose (Day 1). Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 4, 8, 12 and 16

  14. Percentage of Participants With at Least a 4 Units Improvement From Baseline of St. George's Respiratory Questionnaire (SGRQ)

    SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is defined as the latest available assessment prior to first dose (Day 1). A responder is defined as a change from Baseline of <= -4 at the given time point. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 4, 8, 12 and 16

  15. Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1)

    Pre-bronchodilator FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is defined as the latest available assessment prior to first dose (Day 1) and change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 2, 4, 6, 8, 10, 12, 14 and 16

  16. Change From Baseline in Mean Morning Peak Expiratory Flow (PEF) and Mean Evening PEF

    PEF is maximum speed of expiration measured, using spirometer. The device was distributed to participants at Visit 1, to measure PEF twice-daily (morning upon waking \& in the evening just before going to bed). Participants were encouraged to perform morning \& evening PEF measurements before the use of any long-acting beta-agonists (LABAs) or rescue medication. Highest of 3 values were recorded in eDairy.Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Mean PEF was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16).Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment

    Measured: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16.

  17. Change From Baseline in Mean Daytime Asthma Symptom Score Over Each Four Weeks of the 16 Week Treatment Period

    Asthma symptoms experienced by participants during the day was recorded in e-Diary every evening before going to bed in form of scores on a 5-point rating scale. Scores ranged from 0=no daytime asthma symptoms to 4=very severe daytime asthma symptoms. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. The mean asthma symptom score was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16

  18. Change From Baseline in Mean Daily Rescue Medication Use (Albuterol/Salbutamol)

    The mean number of inhalation of rescue medication (albuterol/salbutamol) used to relieve symptoms immediately during the day and night was recorded in eDiary from Baseline until Week 16. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants with at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. The mean rescue medication use was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16

  19. Change From Baseline in Percent Night-time Awakenings Due to Asthma Symptoms Requiring Rescue Medication Use

    Participant captured night-time awakenings (yes/no) and use of rescue medication during these awakenings (yes/no) was recorded in e-Diary each morning. Percentage of night-time awakenings is calculated by number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data available*100. Baseline was calculated over the last 7 days of run-in period prior to Visit 2 (Week 0). Participants having at least 4 full days of data in the last 7 days of run-in were included. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Night-time awakenings due to asthma symptoms requiring rescue medication was calculated for each participant during the four weekly periods (Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16). Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1-4; Weeks 5-8, Weeks 9-12 and Weeks 13-16

  20. Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO)

    FeNO was assessed as a measure of airway inflammation using a handheld electronic device. The measurements recorded were according to standardized procedures by the American Thoracic Society and the European Respiratory Society Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide. FeNO measurements were obtained prior to FEV1 assessments. Participants did not use their rescue medication for at least 6 hours before each FeNO assessment, unless essential for clinical need. Baseline is defined as the latest available assessment prior to first dose (Day 1). Percent change from Baseline is calculated as ratio to Baseline minus one and multiplied by 100. Data is presented for primary estimand which includes all data collected, except for data collected after the date of loss of asthma control or early withdrawal from study treatment.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14 and 16

  21. Number of Participants Reporting Serious Adverse Events (SAEs) and Non-Serious Adverse Events (Non-SAEs)

    A non-SAE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment were categorized as SAE.

    Measured: Up to Week 16

  22. Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

    DBP and SBP were measured in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data for change from Baseline for post dose values have been presented.

    Measured: Baseline and Week 0 (Post-dose), Week1, Week 2, Week 4 (Pre and Post dose), Week 6, Week 8 (Pre and Post dose), Week 10, Week 12 (Pre and Post dose), Week 14, Week 16, Week 20, Week 24 and Week 28

  23. Change From Baseline in Pulse Rate (PR)

    Pulse rate was measured in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Data for change from Baseline for post dose values have been presented.

    Measured: Baseline and Week 0 (Post-dose), Week1, Week 2, Week 4 (Pre and Post dose), Week 6, Week 8 (Pre and Post dose), Week 10, Week 12 (Pre and Post dose), Week 14, Week 16, Week 20, Week 24 and Week 28

  24. Change From Baseline Between Post-dose and Pre-dose in DBP and SBP

    DBP and SBP was measured pre-dose and post-dose in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4, 8 and 12

  25. Change From Baseline Between Post-dose and Pre-dose in Pulse Rate

    Pulse rate was measured pre-dose and post-dose in semi-supine position after 5 minutes rest. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4, 8 and 12

  26. Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia [QTcF] Interval and RR Interval

    Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures PR interval, QRS duration, uncorrected QT interval, QTcF interval and RR interval. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Week 0 (Post-dose), Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16

  27. Change From Baseline in ECG Heart Rate

    Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures heart rate. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Week 0 (Post-dose), Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16

  28. Change From Baseline in QRS Axis

    Triplicate 12-lead ECGs were recorded with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures QRS axis. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Week 4 (Pre and Post dose), Week 8 (Pre and Post dose), Week 12 (Pre and Post dose) and Week 16

  29. Change Between Pre-dose and Post-dose of PR Interval, QRS Duration, Uncorrected QT Interval, QTcF Interval and RR Interval

    Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures PR interval, QRS duration, uncorrected QT interval, QTcF interval and RR interval. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4, 8 and 12

  30. Change Between Pre-dose and Post-dose of Heart Rate

    Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures heart rate. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4, 8 and 12

  31. Change Between Pre-dose and Post-dose of QRS Axis

    Triplicate 12-lead ECGs were recorded pre-dose and post-dose with participant in semi-supine position after 5 minutes rest. At each time point ECG was taken using an ECG machine that automatically measures QRS axis. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4, 8 and 12

  32. Change From Baseline in Maximum, Minimum and Average Changes in Heart Rate

    Using a Holter monitor, maximum, minimum and average changes in heart rate was recorded at Baseline, Weeks 0, 4 and 12 through 24 hours. Participants with analyzable time of at least 16 hours were evaluated. Baseline is the value from the screening visit assessment. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4 and 12

  33. Change From Baseline in Supraventricular Couplets, Supraventricular Ectopics, Supraventricular Runs, Supraventricular Singles, Ventricular Couplets, Ventricular Ectopics, Ventricular Runs, Ventricular Singles

    Using a Holter monitor, supraventricular couplets, supraventricular ectopics, supraventricular runs, supraventricular singles, ventricular couplets, ventricular ectopics, ventricular runs, ventricular singles were recorded at Baseline, Weeks 0, 4 and 12 through 24 hours. Participants with analyzable time of at least 16 hours were evaluated. Baseline is the value from the screening visit assessment. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 0, 4 and 12

  34. Change From Baseline in Clinical Chemistry Parameter: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Gamma- Glutamyl Transferase (GGT) and Creatine Kinase (CK)

    Blood samples were collected for the analysis of clinical chemistry parameters including AST, ALT, ALP, GGT and CK at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 2, 4, 8, 12, 16 and 28

  35. Change From Baseline in Clinical Chemistry Parameters: Glucose, Potassium, Sodium, Calcium, Phosphate, Chloride, Urea and Carbon Dioxide (CO2)

    Blood samples were collected at given time points to assess clinical chemistry parameters including glucose, potassium, sodium, calcium, Phosphate, chloride, urea and CO2 levels. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 2, 4, 8, 12, 16 and 28

  36. Change From Baseline in Clinical Chemistry Parameters: Creatinine, Total Bilirubin and Direct Bilirubin

    Blood samples were collected for the analysis of clinical chemistry parameters including total bilirubin, creatinine and direct bilirubin at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 2, 4, 8, 12, 16 and 28

  37. Change From Baseline in Clinical Chemistry Parameters: Total Protein and Albumin

    Blood samples were collected at given time points to assess clinical chemistry parameters including total protein and albumin levels. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 2, 4, 8, 12, 16 and 28

  38. Change From Baseline in Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets

    Blood samples were collected at given time points to assess hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, leutrophils, monocytes, and platelets . Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  39. Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume

    Blood samples were collected for the analysis of erythrocyte mean corpuscular volume at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  40. Change From Baseline in Hematology Parameter: Erythrocytes

    Blood samples were collected for the analysis of erythrocytes at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  41. Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected for the analysis of hemoglobin level at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  42. Change From Baseline in Hematology Parameter: Hematocrit Level

    Blood samples were collected for the analysis of hematocrit at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  43. Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin

    Blood samples were collected for the analysis of mean corpuscular hemoglobin at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  44. Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin Concentration

    Blood samples were collected for the analysis of mean corpuscular hemoglobin concentration at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  45. Change From Baseline in Hematology Parameter: Erythrocytes Distribution Width (%)

    Blood samples were collected for the analysis of Erythrocytes Distribution Width (%) at indicated time points. Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  46. Change From Baseline in Cardiac Marker: N-Terminal ProB-type Natriuretic Peptide

    Blood samples were collected for the analysis of N-Terminal ProB-type Natriuretic Peptide at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  47. Change From Baseline in Cardiac Marker: Cardiac Troponin I

    Blood samples were collected for the analysis of Troponin I at indicated time points.Baseline is defined as the most recent recorded value before dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

    Measured: Baseline and Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 28

  48. Number of Participants With Incidence and Titres of Anti- GSK3772847 Antibodies

    Blood samples were collected at given time points and the presence of anti-GSK3772847 antibodies were assessed using a a tiered approach including a screening assay, a confirmation assay and calculation of titer. Data for participants who showed positive results for confirmation assay has been presented

    Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24 and 28

  49. Serum Concentrations of GSK3772847

    Blood samples were collected at given time points to evaluate pharmacokinetics (PK) of GSK3772847 in participants with moderately severe asthma.

    Measured: Weeks 2, 4 (Pre-dose), 8 (Pre-dose), 12 (Pre-dose and Post-dose), 16, 20, 24 and 28

  50. Percent Change From Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration

    Blood samples were collected at given time points to measure free soluble ST2 concentration. Baseline is defined as the latest available assessment prior to first dose (Day 1). Analysis was performed using mixed model repeated measures. Percent change from Baseline is calculated as ratio to Baseline minus 1 and multiplied by 100.

    Measured: Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16

  51. Percent Change From Baseline in Total Soluble ST2 Concentration

    Blood samples were collected at given time points to measure total soluble ST2 concentration. Baseline is defined as the latest available assessment prior to first dose (Day 1). Analysis was performed using mixed model repeated measures. Percent change from Baseline is calculated as ratio to Baseline minus 1 and multiplied by 100.

    Measured: Baseline and Week 4 (Pre-dose), Week 8 (Pre-dose), Week 12 (Pre-dose) and Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2017
  2. Study start14 Sep 2017
  3. Primary completion15 Feb 2019
  4. Study completion15 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This will be a parallel intervention model in which GSK3772847 and placebo will be administered in parallel manner to randomized subjects.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
165 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03207243
Sponsor's protocol ID
207597
Other IDs
2017-001072-34, 2017
Status last verified
Feb 2020
First submitted
29 Jun 2017
Last updated
2 Mar 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK3772847, Fluticasone propionate/salmeterol and Fluticasone propionate in people with Asthma, run by GlaxoSmithKline at 64 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Canada, Russia, Mexico, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Loss of Asthma Control Over Weeks 0-16 (time frame: Up to Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03207243.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in