To evaluate the effect of tezepelumab as compared with placebo on COPD exacerbations in subjects with moderate to very severe COPD
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: Rate of moderate or severe COPD exacerbations
Primary outcome measure: Moderate or severe COPD exacerbation rate ratio
(tezepelumab vs placebo)
Supportive endpoint: Rate of moderate (excluding exacerbations treated only
with antibiotics) or severe COPD exacerbations
Supportive Measure: Moderate (excluding exacerbations treated only with
antibiotics) or severe COPD exacerbation rate ratio (tezepelumab vs placebo)
Secondary outcome
To evaluate the effect of tezepelumab compared with placebo on time to first
moderate/severe exacerbation
-Time to first moderate or severe COPD exacerbation
To evaluate the effect of tezepelumab as compared with placebo on severe COPD
exacerbations
-Rate of severe COPD excerbations
Secondary Objectives
- To evaluate the effect of tezepelumab compared with placebo on time to first
exacerbation
- To evaluate the effect of tezepelumab as compared with placebo on severe COPD
exacerbations
- To evaluate the effect of tezepelumab as compared with placebo on
prebronchodilator (BD) lung function
- To evaluate the effect of tezepelumab as compared with placebo on respiratory
health status/health-related quality of life
- To evaluate the pharmacokinetics (PK) and immunogenicity of tezepelumab
Background summary
Chronic obstructive pulmonary disease (COPD) is a progressive disease and a
significant cause of morbidity and mortality worldwide. In contrast to other
chronic diseases, COPD is increasing in prevalence and is projected to be the
third leading cause of death and disability worldwide by 2020.
Acute exacerbations of COPD (AECOPD) are responsible for a large portion of the
economic burden of COPD. In addition to a substantial economic burden, AECOPDs
are also responsible for much of the morbidity and mortality from COPD.
Patients with frequent AECOPD show associated increased airway inflammation and
accelerated decline in lung function compared with patients with infrequent
exacerbations.
Tezepelumab is a fully human immunoglobulin G (IgG) monoclonal antibody (mAb)
directed against thymic stromal lymphoprotein (TSLP). Tezepelumab binds to
human TSLP and prevents its interaction with the TSLP receptor (TSLPR). The
hypothesis for the mechanism of action of tezepelumab in COPD is two-fold.
First, because TSLP is one of the earliest responses to airway damage caused by
a range of stimuli, inhibition of TSLP is expected to prevent the acute
response to epithelial
damage and prevent COPD exacerbations. Secondly, given that TSLP is an upstream
and pleiotropic cytokine, the blockade of TSLP is anticipated to have broad
impact on the spectrum of acute and chronic airway inflammatory responses seen
in COPD. Both effects are expected to reduce COPD exacerbations and improve
COPD symptoms
It is hypothesized that inhibition of upstream TSLP by tezepelumab will be
effective in reducing airway inflammation in patients with COPD and reducing
annualized COPD exacerbation rates. The purpose of the present study is to
investigate the ability of tezepelumab versus placebo to enable reduction of
the annualized COPD exacerbation rate in subjects with moderate to very severe
COPD receiving standard maintenance therapy.
Study objective
To evaluate the effect of tezepelumab as compared with placebo on COPD
exacerbations in subjects with moderate to very severe COPD
Study design
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled,
parallel group study to evaluate the efficacy and safety of tezepelumab 420 mg
administered by SC injection Q4W in subjects with moderate to very severe COPD
receiving triple inhaled maintenance therapy (ICS, LABA and LAMA), and having
had >=2 documented COPD exacerbations in the 12 months prior to visit 1.
Approximately 30% of subjects will have had at least 1 severe exacerbation (an
exacerbation resulting in hospitalization) within the 12 months prior to Visit
1. Approximately 40% of subjects will have had >=3 exacerbations within the 12
months prior to Visit 1.
The study will randomize approximately 338 subjects 1:1 to the treatment arms,
stratified by region, and number of prior exacerbations. Approximately 60% of
the subjects will be targeted to have >=150 eosinophils/µL at enrolment, with a
maximum of approximately 40% below this threshold.
Induced sputum analysis will be performed in a subset of subjects and in a
limited number of sites globally. The aim of the induced sputum subset analysis
is to explore the mechanisms by which tezepelumab might reduce COPD
excerbations. In these same selected subjects, analysis of nasal lining fluid
and epithelial transcriptomics will also be performed.
Intervention
Subjects will be randomized in a 1:1 ratio to either 420 mg of tezepelumab or
matching placebo both administered Q4W SC. During treatment period, IP will be
administered from day 0 until week 48.
Study burden and risks
The subject is asked to visit the site at least 18 times. The visit time will
last maximal 4 hours.
The subject will be contacted by telephone at least 1 time at the end of the
study. This telephone call will last maximally 15 minutes
Blood samples will be taken in this study. The total volume of blood that will
be collected is approximately 285-450 ml.
The subject will undergo physical examinations at every hospital visit.
The subject will undergo a spirometry test at least 8 times during the study
The subject will undergo a FeNo test at least 8 times during the study
The subject (only in the substudy) will undergo a sputum test at least 2 times
during the study
The subject (only in the substudy) will undergo a nasal lining fluid test at
least 6 times during the study.
One X-ray of the thorax will be done
The subject will be asked to fill out questionnaires at all hospital visits
with a maximum of 8 times.
Woman of child bearing potential have to provide a urine sample to test for
pregnancy at screening and each time before administration of studymedication (
14 times)
The subject must fill out questionnaires every day (in the morning and evening)
in an e-Diary. This takes approximately 10 minutes a day.
The subject will receive the study medication at least 13 times. The study
medication may cause allergic reactions. A study physician will supervise the
administration of the study drug and will observe the subject at the study
center for at least 2 hours after each injection. Treatment will be immediately
available if a subject has symptoms related to study drug administration. There
is a possibility of an allergic reaction of study medication. Therefore, the
subject must be in observation at the hospital.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
1.Female or Male subjects between 40-80 years
2.History of moderate to severe physician-diagnosed COPD for at least 12 months
prior to enrollment with a post-bronchodilator FEV1 > 20% and < 80% of
predicted normal value
3.History of at least 2 documented moderate to severe COPD exacerbation's,
within 2-52 weeks prior to enrollment
4.CAT score of > 15 at Visit 1
5.Subjects should have evidence of having been treated with triple (medium or
high dose ICS/LABA/LAMA) therapy for COPD throughout the year prior to
enrollment, the dose should be stable for 3 months prior to screening visit.
6.Current smoker or ex-smoker with a tobacco history of > 10 pack years
7.If on allergen-specific immunotherapy, subjects must be on a maintenance dose
and schedule for at least 2 months prior to screening visit.
8.If on theophylline or roflumilast, subjects must be on maintenance treatment
for at least 12 months prior to screening visit and on stable dose 3 months
prior to screening visit.
Exclusion criteria
1) Clinically important pulmonary disease other than COPD, as judged by
Investigator.
2) Current or previous asthma diagnosis
3) Any disorder, including, but not limited to, cardiovascular,
gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious
(including risk factors for pneumonia), endocrine, metabolic, haematological,
immune, psychiatric, or major physical impairment that is not stable
4) Treatment with systemic corticosteroids and/or antibiotics, and/or
hospitalization for a COPD exacerbation within 14 days prior to enrollment
(Visit 1) based on last dose of corticosteroids or last date of
hospitalization, whichever occurred later.
5) History of clinically significant infection (excluding pneumonia), acute
upper or lower respiratory infection, requiring antibiotics or antiviral
medication within 14 days prior to enrollment (Visit 1) or during the screening
period.
6) History of pneumonia requiring antibiotics or antiviral medication within 28
days prior to enrollment (Visit 1) or during the screening period.
7) History of allergy or reaction to any component of tezepelumab.
8) History of anaphylaxis to any other biologic therapy.
9) History of alcohol or drug abuse within the past year.
10) History of cancer:
11) Subjects with tuberculosis (TB).
12) Major surgery within 8 weeks prior to Visit 1 or planned surgical
procedures requiring general anaesthesia
13) Pregnant, breastfeeding, or lactating women.
14) The chest/lungs with pathology that precludes the patient*s ability to
complete the study.
15) The patient has active Covid 19 infection during the screening period.
16) Receipt of any COVID-19 vaccine 28 days prior to date of randomization
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 |
|---|---|
| Other | 04039113 |
| EudraCT | EUCTR2019-001363-67-NL |
| CCMO | NL70257.100.19 |