Primary:To evaluate the efficacy of 3 doses of GSK3772847 (administered every 4 weeks) compared with placebo in moderate to severe asthma participants with allergic fungal airway disease (AFAD) who are currently on Standard of Care (SoC) Secondary:…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline (Week 0) in blood eosinophils over time. Change from
baseline (Week 0) in fractional exhaled nitric oxide (FeNO) over time
Secondary outcome
Serum concentrations of GSK3772847. Serum levels of free and total soluble ST2.
anti-GSK3772847 antibodies. ACQ-5 and AQLQ questionnaires. Change from baseline
in FEV1. Adverse events.
Background summary
GSK3772847 (formerly CNTO 7160, in-licensed from Janssen) is a human IgG2 sigma
isotype antibody that binds to the interleukin-33 receptor. Blockade of the
IL-33 receptor presents a potential novel treatment for severe asthma as an
add-on to standard of care. Agents targeting this mechanism could be expected
to have effects on both T2-driven and non-T2-driven disease.
Allergic fungal airway disease (AFAD) is defined as IgE sensitisation to
particularly Aspergillus fumigatus. Clinical data suggest increased IL-33
levels in bronchoalveolar fluid and endobronchial biopsy at baseline disease of
children with severe asthma with fungal sensitization. and in lung tissue
samples from patients with allergic bronchopulmonary aspergillosis. Recent data
reported an association between IgE sensitisation to fungi like Aspergillus
fumigatus and the presence of lung damage as demonstrated by high-resolution
computed tomography scanning in moderate to severe asthma. This study aims to
evaluate the effects of GSK3772847 in moderate to severe asthma participants
with AFAD on top of standard of care.
Study objective
Primary:
To evaluate the efficacy of 3 doses of GSK3772847 (administered every 4 weeks)
compared with placebo in moderate to severe asthma participants with allergic
fungal airway disease (AFAD) who are currently on Standard of Care (SoC)
Secondary:
PK. PD. Antibodies against GSK3772847. Health status. Lung function. Safety and
tolerability.
Study design
Double blind (sponsor open) placebo-controlled, stratified, parallel group
study to evaluate safety and efficacy of GSK3772847 (3 IV infusions 50 mL, each
4 weeks apart).
Randomization 1:1 to GSK3772847 and placebo on top of standard treatment.
2 weeks run-in on standard treatment. Study treatment 12 weeks. Follow-up 12
weeks.
46 subjects.
Intervention
Treatment with GSK3772847 or placebo on top of standard therapy.
Study burden and risks
Risk: Adverse events of GSK3772847.
Burden:
8 visits in 28 weeks.
Complete physical examination: once.
Blood tests: 7 visits, 380 mL in total.
Pregnancy test: 6 times (urine or blood).
Sputum induction: 2 times.(if failed: test should be repeated at next occasion;
so at most 4 times in total).
ECG: 5 visits.
Diary: daily, rescue medication, change in medication, medical problems.
Questionnaires (1-2): 6 times.
FeNO test: 6 times.
Lung function: 6 times.
Optional blood sample (6 mL) for genetic research.
Huis ter Heideweg 62
Zeist 3715 LZ
NL
Huis ter Heideweg 62
Zeist 3715 LZ
NL
Listed location countries
Age
Inclusion criteria
• Males and females >=18 years of age.
• Documented diagnosis of moderate to severe asthma for >=12 months.
• Treated with inhaled corticosteroid and long-acting beta-2-agonist for at least 4 months (>=500 ug/day fluticasone propionate or equivalent).
• Pre-bronchodilator FEV1 35-79% of predicted.
• FeNO >=25ppb at Screening.
• ACQ-5 score >=1.5 at Screening
• Blood eosinophils >=300 cells/microliter at Screening.
• Evidence of allergic fungal airway disease. See protocol page 38 for details.
• Female participants of childbearing potential: see protocol page 38-39 for details..
Exclusion criteria
• Concurrent respiratory diseases. See protocol page 39 for details.
• History of chronic or recurrent non-pulmonary infectious disease or ongoing non-pulmonary infection. See protocol page 39 for details.
• Serious infection within 8 weeks of enrolment. See protocol page 39 for details.
• Clinically significant organic heart disease. See protocol page 39 for details.
• Eosinophilic diseases. See protocol page 40 for details.
• Prior or concomitant therapy as in Table 2 on protocol page 40.
• Abnormal and clinically significant ECG findings as in Table 3 on protocol page 41.
• Current smokers or former smokers with a smoking history >=10 pack years.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003544-20-NL |
| CCMO | NL65598.100.18 |
| Other | www.gskclinicalstudyregister.com onder studieID 207972 |