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

NCT03393806 | Terminated Phase 2 Results

• 2 other identifiers: 2079722017-003544-20
• Study Type: interventional
• Target: 17
• Locations: 4 countries
• Sites: 18

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.

Conditions

Asthma

Keywords

Asthma Control Questionnaire; Allergic fungal airway disease; Asthma Quality of Life Questionnaire; Holter monitoring; Asthma

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Blood Eosinophils Over Time

  Blood samples were collected at the indicated time points for assessment of blood eosinophil cell count. Baseline is the most recent recorded value before dosing on Day 1. Percent change from Baseline is calculated as (Ratio to Baseline minus 1)\*100, where ratio to Baseline is the value at specified time point divided by Baseline value.

  Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12

• Percent Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Over Time

  FeNO was assessed using a handheld electronic device. The measurements were obtained in accordance with 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. Participants did not use their rescue medication for at least 6 hours before each FeNO assessment, unless essential for clinical need. Baseline is the most recent recorded value before dosing on Day 1. Percent change from Baseline is calculated as (Ratio to Baseline minus 1)\*100, where ratio to Baseline is the value at specified time point divided by Baseline value.

  Baseline (Day 1, pre-dose), Weeks 2, 4, 8 and 12

Secondary Outcomes (18)

• Serum Concentrations of GSK3772847

  Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose), Week 12 and Week 24

• Serum Levels of Free Suppressor of Tumorigenicity 2 (ST2)

  Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12

• Serum Levels of Total Soluble ST2

  Baseline, Week 0 (post-dose), Week 2, Week 4 (pre-dose), Week 8 (pre-dose and post-dose) and Week 12

• Number of Participants With Positive Anti-GSK3772847 Antibodies Post-dosing

  Weeks 0, 2, 4, 8, 12 and 24

• Number of Participants for Whom Titers of Anti-GSK3772847 Antibodies Was Performed

  Weeks 0, 2, 4, 8, 12 and 24

Study Arms (2)

Participants receiving GSK3772847

EXPERIMENTAL

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

Drug: GSK3772847

Participants receiving placebo

PLACEBO COMPARATOR

Participants will be randomized to receive matching placebo as IV infusion

Drug: Placebo

Interventions

GSK3772847 DRUG

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.

Participants receiving GSK3772847

Placebo DRUG

Commercially sourced sterile normal saline will be provided as Placebo

Participants receiving placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (18)

GSK Investigational Site

Brest, 29609, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

GSK Investigational Site

Izhevsk, 426063, Russia

Location

GSK Investigational Site

Kemerovo, 650000, Russia

Location

GSK Investigational Site

Moscow, 105275, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Saint Petersburg, 194291, Russia

Location

GSK Investigational Site

Saint Petersburg, 194354, Russia

Location

GSK Investigational Site

Saint Petersburg, 196240, Russia

Location

GSK Investigational Site

Ulyanovsk, 432063, Russia

Location

GSK Investigational Site

Wythenshawe, Greater Manchester, M23 9LT, United Kingdom

Location

GSK Investigational Site

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

GSK Investigational Site

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

Bradford, BD9 6RJ, United Kingdom

Location

GSK Investigational Site

Edgbaston, B15 2GW, United Kingdom

Location

Related Publications (1)

• Akinseye C, Crim C, Newlands A, Fairman D. Efficacy and safety of GSK3772847 in participants with moderate-to-severe asthma with allergic fungal airway disease: A phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial. PLoS One. 2023 Feb 3;18(2):e0281205. doi: 10.1371/journal.pone.0281205. eCollection 2023.

  PMID: 36735745 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

melrilimab

Condition Hierarchy (Ancestors)

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

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 1:1 ratio to receive either 10 mg/kg GSK3772847 or matching placebo intravenously.

Study Record Dates

• First Submitted: January 3, 2018
• First Posted: January 9, 2018
• Study Start: April 18, 2018
• Primary Completion: October 9, 2019
• Study Completion: January 6, 2020
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

FR (3); NL (1); GB (6); RU (8)