A Phase 2a, open label, two-part study to evaluate the mechanism of action of itepekimab (anti-IL-33 mAb) on airway inflammation in patients with chronic obstructive lung disease (COPD)

Phase 2

Recruiting

Conditions: Chronic bronchitis
Chronic Obstructive Pulmonary Disease
COPD
10006436

Registration Number: NL-OMON52084

Lead Sponsor: Sanofi BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 3

Inclusion Criteria

- Participant must be 40 to 70 years of age inclusive
- Physician diagnosis of COPD for at least 1 year (based on the Global
Initiative for
Chronic Obstructive Lung Disease [GOLD] definition).
- Smoking history of >=10 pack-years
-- For former smokers: Participants who report that they are not currently
smoking, and
smoking cessation must have occurred >=6 months prior to Screening (Visit 1)
with an
intention to quit permanently.
-- For current smokers (not eligible for Part A): Participants who report that
they are
currently smoking tobacco (participant smoked at least 5 cigarettes per day on
average
during the past 7 days) at Screening (Visit 1) and at Baseline, and who are not
currently participating in, or planning to initiate, a smoking cessation
intervention at
Screening (Visit 1) or during the screening period.
- Participant-reported history of signs and symptoms of chronic bronchitis
(chronic
productive cough for at least 3 months in the year before screening in a
participant in
whom other causes of chronic cough [eg, inadequately treated gastroesophageal
reflux or
chronic rhinosinustis; or clinical diagnosis of bronchiectasis] have been
excluded).
- Documented or self-reported history of exacerbation having had >=1 moderate or
severe
exacerbation within the 5 years prior to Screening (Visit 1), with at least 1
exacerbation
treated with systemic corticosteroids:
-- Moderate exacerbations are defined as an acute worsening of respiratory
symptoms
that requires either systemic corticosteroids (intramuscular [IM], intravenous
[IV], or
oral) and/or antibiotics.
-- Severe exacerbations are defined as AECOPD that require hospitalization or
observation for >24 hours in emergency department/urgent care facility.
- Participants treated with SoC controller therapy for >=3 months before
Screening (Visit 1)
and at a stable dose and regimen of controller therapy for at least 1 month
before the
screening visit AND during the screening period, including either: triple
therapy with LAMA
+ LABA + ICS or double therapy with ICS + LABA or LABA + LAMA or ICS + LAMA, or
monotherapy with LABA or LAMA.
- Participants who have received appropriate vaccination according to local
recommendations against severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), administered a minimum of 1
week
prior to Screening (Visit 1).
- Body mass index (BMI) >=18 kg/m2
- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and
at least one of the following conditions applies:
-- Not a women of child-bearing potential (WOCBP) or
-- A WOCBP who agrees to follow the contraceptive guidance during the
intervention
period and for at least 20 weeks after the last dose of study intervention.

Exclusion Criteria

- Current diagnosis or previously confirmed diagnosis of asthma according to
the Global
Initiative for Asthma (GINA) guidelines unless asthma resolved before 18 years
of age and has not returned.
- For former smokers (Parts A and B): Active smoking or vaping of any products
(eg,
nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit
1) or during
the screening period.
For current smokers (Part B): vaping of any products (eg, nicotine, THC) within
6 months
prior to Screening (Visit 1) or during the screening period.
- Participants who are expected to be regularly exposed to environmental (ie,
second
hand) tobacco smoke in an indoor setting during the screening or treatment
periods
(former smokers only)
- Clinically significant new abnormal electrocardiogram (ECG) within 6 months
before or at
Screening (Visit 1) that may affect the participant*s participation in the
study.
- Clinically significant and current pulmonary disease other than COPD, eg,
sarcoidosis,
interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of
a-1 anti-trypsin
deficiency, or another diagnosed pulmonary disease.
- Diagnosis of cor pulmonale, evidence of right cardiac failure, or
moderate-to-severe
pulmonary hypertension.
- Participants who require more that 2L/min of long-term treatment with oxygen
at rest. Participants who use up to 4L/min of supplemental oxygen during
exercise may enroll. Oxygen during sleep is allowed.
- Participants who receive long-term treatment with oxygen or a low oxygen
saturation on
room air at rest.
- Hypercapnia that requires bi-level positive airway pressure (BiPAP).
- Moderate or severe exacerbation of COPD (AECOPD) within 8 weeks prior to
Screening
(Visit 1) or during the screening period.
- Prior history of pneumonectomy, lobectomy, segmentectomy, or therapeutic
bronchoscopy procedure (including bronchoscopic volume reduction).
Note: Prior history of surgical lung biopsy or wedge resection are not
exclusion criteria.
- Any surgery or major procedures (including those requiring conscious
sedation) planned
to occur during the study. Minor skin procedures are allowed.
- Unstable ischemic heart disease, including acute myocardial infarction within
1 year
before Screening (Visit 1), or unstable angina within 6 months before Screening
(Visit 1)
or during the screening period.
- Cardiac arrhythmias, including paroxysmal (eg, intermittent) atrial
fibrillation. Participants
with isolated premature ventricular contractions (PVCs) or premature atrial
contractions
(PACs) may be considered for inclusion.
- Cardiomyopathy, as defined by Stage III-IV (New York Heart Association)
cardiac failure,
or other relevant cardiovascular disorder that that may affect the
participant*s participation
in the study.
- Any underlying disease requiring the use of prophylaxis for endocarditis.
- Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or
diastolic BP
>110 mm Hg with or without use of antihypertensive therapy).
- Participants with active tuberculosis (TB), latent TB, a history of
incompletely treated TB,
suspected extrapulmonary TB infection (TBI), or who are at high risk of
contracting TB
(such as close contact with individuals with active or latent TB) or r

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part A: Log2 relative change from baseline in gene expression in endobronchial<br /><br>biopsies at Week 12<br /><br><br /><br>Part B: Change from baseline in itepekimab treatment normalized enrichment<br /><br>score (NES) developed in Part A in endobronchial biopsies at Week 12</p><br>

Secondary Outcome Measures

Name	Time	Method