To evaluate the effect of MEDI3506 as compared with placebo on pulmonary function in subjects with moderate to severe COPD and chronic bronchitis.
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the effects of MEDI3506 compared with placebo on pulmonary function
in participants with COPD and chronic bronchitis, the change from baseline to
Week 12 in pre-BD FEV1 measured in clinic will be used as primary endpoint.
Secondary outcome
The study uses secondary outcomes to gather evidence to support the mode of
action of MEDI3506, concentrating on lung physiology, mucus, cough, and ePROs
related to symptoms and disease impact. Therefore the study includes secondary
outcomes to assess the PK of MEDI3506 in participants with COPD and chronic
bronchitis; to asses the immunogenicity of MEDI3506 compared with placebo in
participants with COPD and chronic bronchitis; to assess the effect of MEDI3506
on COPDCompEx event in participants with COPD and chronic bronchitis; to assess
the effect of MEDI3506 compared with placebo on respiratory symptoms in
participants with COPD and chronic bronchitis; to assess the effect of MEDI3506
compared with placebo on disease impact in participants with COPD and chronic
bronchitis; to assess the effect of MEDI3506 compared with placebo on airway
resistance and reactance in participants with COPD and chronic bronchitis; and
to evaluate the effect of MEDI3506 compared with placebo on objective cough
measures in participants with COPD and chronic bronchitis.
Background summary
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of
death in the world. The disease is characterized by persistent respiratory
symptoms and airflow limitation that is due to airway and/or alveolar
abnormalities. COPD is not fully reversible, usually progressive and associated
with an enhanced chronic inflammatory response in the lung. Patients with
active chronic bronchitis symptoms bear a greater burden of disease than those
without and are characterized by more rapid loss of lung function, increased
mortality and increased risk of exacerbation. Interleukin-33 (IL-33) expression
is upregulated in the lungs of patients with COPD, is inversely correlated with
lung function, and has a role in inflammatory and epithelial processes in COPD.
MEDI3506 is a monoclonal antibody that binds to IL-33 and potently and
specifically blocks all forms of IL-33 to prevent their signaling. Its mode of
action is hypothesized to impact airway inflammation, mucus and cough symptoms
and lung function endpoints in COPD, and through modification of these factors,
reduce frequency and severity of exacerbations. The purpose of the present
study is to test the hypothesis that MEDI3506 will improve lung function in
participants with COPD and chronic bronchitis.
Study objective
To evaluate the effect of MEDI3506 as compared with placebo on pulmonary
function in subjects with moderate to severe COPD and chronic bronchitis.
Study design
This is a Phase II, randomized, double-blind, placebo-controlled,
proof-of-concept study to assess the efficacy, safety, and tolerability of
MEDI3506 600 mg administered by SC injection Q4W in participants with moderate
or severe COPD receiving Standard of Care as maintenance therapy, which is dual
therapy (ICS + LABA, or LABA + LAMA) or triple therapy (ICS + LABA + LAMA).
Participants also have a history of *1 moderate or severe acute exacerbation in
the previous 24 months while on stable background treatment, and moderate to
severe chronic bronchitis, with active sputum and cough symptoms. The study
will randomize approximately 322 participants 1:1 to MEDI3506 600 mg SC Q4W or
placebo for 7 doses. The randomization will be stratified by baseline blood
eosinophils (< 300 cells/*L vs * 300 cells/*L) and background medication
(includes ICS vs does not include ICS). Approximately 60% of participants will
be included in the baseline eosinophils < 300 cells/*L strata. At least 70% of
participants will be included in the strata who are receiving ICS.
Intervention
Subjects will be randomized in a 1:1 ratio to either 600 mg of MEDI3506 or
matching placebo both administered Q4W SC. During treatment period, IP will be
administered from day 0 until week 28.
Study burden and risks
The subject is asked to visit the site at least 16 times. During the
intervention period, the subject will receive 7 administrations of study
intervention. The subject will undergo physical examinations at every site
visit. The subject will undergo a spirometry test at least 12 times during the
study. Additionally, nasal mucosal samples (2 times), nasal epithelial lining
fluid (8 times) and spontaneous sputum samples (6 times) will be collected
during site visits. The subject (only in the sub-study) will undergo a CT-scan
once during the study. The subject must perform spirometry measurements at home
on each day throughout intervention and follow-up periods. The subject must
complete eDiary assessments on each day throughout the intervention and
follow-up periods. Woman of child bearing potential have to provide a urine
sample to test for pregnancy at screening, once during follow-up and each time
before administration of study medication. The study medication may cause
gastrointestinal adverse reactions and serious hypersensitivity. A study
physician will supervise the administration of the study drug and will observe
the subject at the study center for a minimum of 1 to 2 hours after each
injection.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
1. Participant must be 40 to 75 years of age inclusive, at the time of signing
the ICF.
2. Participants who are current or ex-smokers with a tobacco history of * 10
pack-years.
3. Participants who are up-to-date on pneumococcus and influenza vaccines as
per local
treatment guidelines.
4. Participants who have a documented history of COPD for at least 1 year.
5. Participants who have a post-BD FEV1/FVC < 0.70 and a post-BD FEV1 > 30% and
< 80% predicted normal value at screening.
6. Participants who have a physician confirmed participant history of chronic
bronchitis as
defined as presence of cough and sputum on most days for * 3 mos/yr in at least
the 2 year period immediately prior to SV1 (screening).
7. Participants who have an average BCSS score of * 2 in cough and * 2 in
sputum domains
assessed over the 14 days preceding SV3.
8. Participants who have a documented stable regimen of dual therapy (ICS +
LABA or LABA + LAMA) or triple therapy (ICS + LABA + LAMA) for * 3 months prior
to enrolment; there should have been no change in treatment after the previous
exacerbation prior to entering into the study.
9. Participants who have a documented history of * 1 moderate or severe AECOPD
requiring systemic corticosteroids and/or antibiotics for at least 3 days
duration (or 1 injection of depot formulation), or hospitalization for reason
of AECOPD in the previous 24 months prior to screening. A verbal history from
the participant of AECOPD is not sufficient.
10. Participants who are clinically stable and free from an exacerbation of
COPD for 1 month prior to SV1 (screening) and prior to Day 1.
Exclusion criteria
1. Participants with a positive diagnostic nucleic acid test for SARS-CoV-2 at
SV1 or SV2.
2. Participants with a significant COVID-19 illness within 6 months of
enrolment
3. As judged by the investigator, any evidence of any active medical or
psychiatric condition or other reason (at screening [SV1 and SV2] and SV3
[pre-dose]). See exclusion criteria number 3 in the protocol.
4. Asthma as a current or past diagnosis.
5. Clinically important pulmonary disease other than COPD (
6. Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1
of * 400 mL or * 25% of SV1 FEV1.
7. A family history of heart failure defined as either of the following: * 2
first degree relatives with clinically significant heart failure, or * 1 first
degree relative with heart failure known to be heritable (eg, hypertrophic
cardiomyopathy), unless inheritance is excluded by genetic testing.
8. A LVEF < 45% measured by echocardiogram during screening, between the time
of signing informed consent and prior to randomization.
9. History of a clinically significant infection (viral, bacterial, or fungal)
within 4 weeks prior to Day 1 (SV3) (including unexplained diarrhea) or
clinical suspicion of infection at time of dosing.
10. Prior history of/planned: lung pneumonectomy for any reason, or lung
volume reduction procedures (including bronchoscopic volume reduction) for
COPD. Note: Surgical biopsy, or segmentectomy, or wedge resection, or lobectomy
for other diseases would not
be excluded.
11. Long term oxygen therapy.
12. Use of any non-invasive positive pressure ventilation device.
13. Participants with a recent history of, or who have a positive test for TB,
Hep B, Hep C or HIV.
14. Receiving any of the prohibited concomitant medications as specified in the
CSP.
Design
Recruitment
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 | EUCTR2020-000571-20-NL |
| CCMO | NL74611.100.20 |