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

NCT03207243 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2075972017-001072-34
• Study Type: interventional
• Target: 165
• Locations: 6 countries
• Sites: 64

Brief 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. 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

Keywords

Severe asthma; Safety; GSK3772847; Efficacy

Outcome Measures

Primary Outcomes (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.

  Up to Week 16

Secondary Outcomes (51)

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

  Baseline and up to Week 16

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

  Baseline and up to Week 16

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

  Up to Week 16

• Percentage of Participants With Clinically Significant Asthma Exacerbation

  Up to Week 16

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

  Up to Week 6

Study Arms (2)

Subjects receiving GSK3772847

EXPERIMENTAL

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.

Drug: GSK3772847; Drug: Fluticasone propionate/salmeterol; Drug: Fluticasone propionate

Subjects receiving placebo drug

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Fluticasone propionate/salmeterol; Drug: Fluticasone propionate

Interventions

GSK3772847 DRUG

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

Subjects receiving GSK3772847

Placebo DRUG

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

Subjects receiving placebo drug

Fluticasone propionate/salmeterol DRUG

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

Subjects receiving GSK3772847; Subjects receiving placebo drug

Fluticasone propionate DRUG

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

Subjects receiving GSK3772847; Subjects receiving placebo drug

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (64)

GSK Investigational Site

Birmingham, Alabama, 35209, United States

Location

GSK Investigational Site

Scottsboro, Alabama, 35768, United States

Location

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Long Beach, California, 90806, United States

Location

GSK Investigational Site

Los Angeles, California, 90017, United States

Location

GSK Investigational Site

Newport Beach, California, 92663, United States

Location

GSK Investigational Site

New Haven, Connecticut, 06510, United States

Location

GSK Investigational Site

Coral Gables, Florida, 33134, United States

Location

GSK Investigational Site

Hialeah, Florida, 33012, United States

Location

GSK Investigational Site

Miami, Florida, 33134, United States

Location

GSK Investigational Site

Miami, Florida, 33135, United States

Location

GSK Investigational Site

Miami, Florida, 33144, United States

Location

GSK Investigational Site

Miami, Florida, 33174, United States

Location

GSK Investigational Site

Miami, Florida, 33175, United States

Location

GSK Investigational Site

Miami, Florida, 33185, United States

Location

GSK Investigational Site

Miami, Florida, 33186, United States

Location

GSK Investigational Site

Winter Park, Florida, 32789, United States

Location

GSK Investigational Site

Adairsville, Georgia, 30103, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21224, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48109-5360, United States

Location

GSK Investigational Site

St Louis, Missouri, 63108, United States

Location

GSK Investigational Site

Rochester, New York, 14642, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27599-7248, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28277, United States

Location

GSK Investigational Site

Mooresville, North Carolina, 28117, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45231, United States

Location

GSK Investigational Site

Toledo, Ohio, 43617, United States

Location

GSK Investigational Site

Tulsa, Oklahoma, 74136, United States

Location

GSK Investigational Site

Medford, Oregon, 97504, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Boerne, Texas, 78006, United States

Location

GSK Investigational Site

Williamsburg, Virginia, 23188, United States

Location

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

GSK Investigational Site

Woodville South, South Australia, 5011, Australia

Location

GSK Investigational Site

Clayton, Victoria, 3168, Australia

Location

GSK Investigational Site

Melbourne, Victoria, 3004, Australia

Location

GSK Investigational Site

Parkville, Victoria, 3050, Australia

Location

GSK Investigational Site

Sherwood Park, Alberta, T8H 0N2, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

GSK Investigational Site

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

GSK Investigational Site

Hamilton, Ontario, L8N 3Z5, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1G 6C6, Canada

Location

GSK Investigational Site

Montreal, Quebec, H2X 3E4, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

GSK Investigational Site

Québec, G1V 4G5, Canada

Location

GSK Investigational Site

Guadalajara, Jalisco, 44100, Mexico

Location

GSK Investigational Site

Cuernavaca, Morelos, 62290, Mexico

Location

GSK Investigational Site

Monterrey, Nuevo León, 64060, Mexico

Location

GSK Investigational Site

Villahermosa, Tabasco, 86035, Mexico

Location

GSK Investigational Site

Mérida, Yucatán, 97070, Mexico

Location

GSK Investigational Site

Mexico City, 03100, Mexico

Location

GSK Investigational Site

México DF, 14050, Mexico

Location

GSK Investigational Site

Chelyabinsk, 454106, Russia

Location

GSK Investigational Site

Kemerovo, 650000, Russia

Location

GSK Investigational Site

Saint Petersburg, 194356, Russia

Location

GSK Investigational Site

Saint Petersburg, 195067, Russia

Location

GSK Investigational Site

Saint Petersburg, 198328, Russia

Location

GSK Investigational Site

Samara, 443068, Russia

Location

GSK Investigational Site

Tomsk, 634028, Russia

Location

GSK Investigational Site

Ulyanovsk, 432063, Russia

Location

GSK Investigational Site

Kyiv, 02002, Ukraine

Location

GSK Investigational Site

Kyiv, 02091, Ukraine

Location

GSK Investigational Site

Kyiv, 03049, Ukraine

Location

MeSH Terms

Conditions

Asthma

Interventions

melrilimab; Fluticasone-Salmeterol Drug Combination; Fluticasone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Salmeterol Xinafoate; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double blind study and subjects and investigator will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a parallel intervention model in which GSK3772847 and placebo will be administered in parallel manner to randomized subjects.

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 2, 2017
• Study Start: September 14, 2017
• Primary Completion: February 15, 2019
• Study Completion: May 15, 2019
• Last Updated: March 2, 2020
• Results First Posted: March 2, 2020

Record last verified: 2020-02

Locations

ME (7); AU (4); CA (9); RU (8); UA (3); US (33)