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

NCT ID: NCT03207243

Last Updated: 2020-03-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

165 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-14

Study Completion Date

2019-05-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Asthma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This will be a parallel intervention model in which GSK3772847 and placebo will be administered in parallel manner to randomized subjects.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
This is a double blind study and subjects and investigator will be masked.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Subjects receiving GSK3772847

Eligible 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.

Group Type EXPERIMENTAL

GSK3772847

Intervention Type DRUG

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

Fluticasone propionate/salmeterol

Intervention Type DRUG

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

Fluticasone propionate

Intervention Type DRUG

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

Subjects receiving placebo drug

Eligible 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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Fluticasone propionate/salmeterol

Intervention Type DRUG

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

Fluticasone propionate

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GSK3772847

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Fluticasone propionate/salmeterol

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

Intervention Type DRUG

Fluticasone propionate

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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).
* 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.


* 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.

Exclusion Criteria

* 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.
* 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.


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

GSK Investigational Site

Birmingham, Alabama, United States

Site Status

GSK Investigational Site

Scottsboro, Alabama, United States

Site Status

GSK Investigational Site

Bakersfield, California, United States

Site Status

GSK Investigational Site

Long Beach, California, United States

Site Status

GSK Investigational Site

Los Angeles, California, United States

Site Status

GSK Investigational Site

Newport Beach, California, United States

Site Status

GSK Investigational Site

New Haven, Connecticut, United States

Site Status

GSK Investigational Site

Coral Gables, Florida, United States

Site Status

GSK Investigational Site

Hialeah, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Miami, Florida, United States

Site Status

GSK Investigational Site

Winter Park, Florida, United States

Site Status

GSK Investigational Site

Adairsville, Georgia, United States

Site Status

GSK Investigational Site

Baltimore, Maryland, United States

Site Status

GSK Investigational Site

Ann Arbor, Michigan, United States

Site Status

GSK Investigational Site

St Louis, Missouri, United States

Site Status

GSK Investigational Site

Rochester, New York, United States

Site Status

GSK Investigational Site

Chapel Hill, North Carolina, United States

Site Status

GSK Investigational Site

Charlotte, North Carolina, United States

Site Status

GSK Investigational Site

Mooresville, North Carolina, United States

Site Status

GSK Investigational Site

Cincinnati, Ohio, United States

Site Status

GSK Investigational Site

Toledo, Ohio, United States

Site Status

GSK Investigational Site

Tulsa, Oklahoma, United States

Site Status

GSK Investigational Site

Medford, Oregon, United States

Site Status

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

Site Status

GSK Investigational Site

Boerne, Texas, United States

Site Status

GSK Investigational Site

Williamsburg, Virginia, United States

Site Status

GSK Investigational Site

Madison, Wisconsin, United States

Site Status

GSK Investigational Site

Woodville South, South Australia, Australia

Site Status

GSK Investigational Site

Clayton, Victoria, Australia

Site Status

GSK Investigational Site

Melbourne, Victoria, Australia

Site Status

GSK Investigational Site

Parkville, Victoria, Australia

Site Status

GSK Investigational Site

Sherwood Park, Alberta, Canada

Site Status

GSK Investigational Site

Vancouver, British Columbia, Canada

Site Status

GSK Investigational Site

Vancouver, British Columbia, Canada

Site Status

GSK Investigational Site

Hamilton, Ontario, Canada

Site Status

GSK Investigational Site

Ottawa, Ontario, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Trois-Rivières, Quebec, Canada

Site Status

GSK Investigational Site

Québec, , Canada

Site Status

GSK Investigational Site

Guadalajara, Jalisco, Mexico

Site Status

GSK Investigational Site

Cuernavaca, Morelos, Mexico

Site Status

GSK Investigational Site

Monterrey, Nuevo León, Mexico

Site Status

GSK Investigational Site

Villahermosa, Tabasco, Mexico

Site Status

GSK Investigational Site

Mérida, Yucatán, Mexico

Site Status

GSK Investigational Site

Mexico City, , Mexico

Site Status

GSK Investigational Site

México DF, , Mexico

Site Status

GSK Investigational Site

Chelyabinsk, , Russia

Site Status

GSK Investigational Site

Kemerovo, , Russia

Site Status

GSK Investigational Site

Saint Petersburg, , Russia

Site Status

GSK Investigational Site

Saint Petersburg, , Russia

Site Status

GSK Investigational Site

Saint Petersburg, , Russia

Site Status

GSK Investigational Site

Samara, , Russia

Site Status

GSK Investigational Site

Tomsk, , Russia

Site Status

GSK Investigational Site

Ulyanovsk, , Russia

Site Status

GSK Investigational Site

Kyiv, , Ukraine

Site Status

GSK Investigational Site

Kyiv, , Ukraine

Site Status

GSK Investigational Site

Kyiv, , Ukraine

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Canada Mexico Russia Ukraine

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2017-001072-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207597

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

GSK2190915 Moderate to Severe Asthma Study
NCT00850642 TERMINATED PHASE2