Study to assess the efficacy, safety, and tolerability of SAR440340/REGN3500/itepekimab in chronic obstructive pulmonary disease (COPD) (AERIFY-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

8 Apr 2021 → 28 Aug 2025

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-512012-21-00

EudraCT number

2020-001819-24

WHO UTN

U1111-1250-2843

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Pharmacogenetic, Pharmacoeconomic, Safety, Pharmacokinetic, Therapy, Efficacy, Pharmacodynamic, Dose response

Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPD

Secondary objectives 15

1. Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD
2. Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD
3. Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD
4. Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD
5. Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD
6. Evaluate the efficacy of itepekimab compared with placebo on Forced Expiratory Volume in 1 second (FEV1) slope in former smokers with moderate-to-severe COPD
7. Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) as assessed by St. George’s Respiratory Questionnaire (SGRQ) in former smokers with moderate-to-severe COPD
8. Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD
9. Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD
10. Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPD
11. Estimate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations in current smokers with moderate-to-severe COPD
12. Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD
13. Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD
14. Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD
15. Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be 40 to 85 years of age inclusive.
2. Physician diagnosis of COPD for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition).
3. 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 1A) with an intention to quit permanently. -- For current smokers: participants who report that they are currently smoking tobacco (participant smoked at least 1 cigarette per day on average during the past 7 days) at Screening (Visit 1A) and who are not currently participating in or planning to initiate a smoking cessation intervention at Screening (Visit 1A) or during Screening period.
4. Participants with moderate-to-severe COPD
5. Participant-reported history of signs and symptoms of chronic bronchitis (chronic productive cough for at least 3 months in the year prior to Screening in a participant in whom other causes of chronic cough [eg, inadequately treated gastroesophageal reflux or chronic rhinosinusitis; or clinical diagnosis of bronchiectasis] has been excluded).
6. Documented history of high exacerbation risk defined as having had ≥2 moderate or ≥1 severe exacerbations within the year prior to Screening (Visit 1A), with at least 1 exacerbation treated with systemic corticosteroids. At least one exacerbation must have occurred while participants were on their current controller therapy: -- Moderate exacerbations will be recorded by the Investigator and are defined as acute worsening of respiratory symptoms that requires either systemic corticosteroids (IM, IV, or oral) and/or antibiotics. -- Severe exacerbations will be recorded by the Investigator and are defined as AECOPD that require hospitalization or observation for >24 hours in emergency department/urgent care facility.
7. Participants with standard of care controller therapy, for ≥3 months prior to Screening (Visit 1A) and at a stable dose of controller therapy for at least 1 month prior to the Screening, including either: inhaled corticosteroid (ICS) + long-acting beta-agonist (LABA), long-acting muscarinic antagonist (LAMA) + LABA or LAMA + LABA + ICS.
8. Body mass index (BMI) ≥18.0 kg/m^2, or BMI ≥16.0 kg/m2 for participants enrolled in East-Asian countries.
9. Female participant 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 19

1. Current diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines, or documented history of asthma unless asthma resolved before 18 years of age and has not recurred.
2. For former smokers: Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
3. For current smokers: vaping of any products (eg, nicotine, THC) within 6 months prior to Screening (Visit 1A).
4. Clinically significant new abnormal electrocardiogram (ECG) within 6 months prior to, or at Screening (Visit 1A) that may affect the participant’s participation in the study.
5. Clinically significant and current pulmonary disease other than COPD, eg, sarcoidosis, interstitial lung disease, bronchiectasis (clinical diagnosis), diagnosis of α-1 anti-trypsin deficiency, or another diagnosed pulmonary disease.
6. Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
7. Hypercapnia requiring bilevel positive airway pressure (BiPAP).
8. Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).
9. 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.
10. Unstable ischemic heart disease, including acute myocardial infarction within the past 1 year prior to Screening, or unstable angina in the 6 months prior to Screening (Visit 1A).
11. Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.
12. Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of anti-hypertensive therapy).
13. 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 received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening (Visit 1A).
14. History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1A).
15. Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection or in contact with known exposure to COVID-19 at Screening (Visit 1A); known history of COVID-19 infection within 4 weeks prior to Screening (Visit 1A); history of requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening (Visit 1A); participants who have had a COVID-19 infection prior Screening (Visit 1A) who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
16. Evidence of acute or chronic infection requiring systemic treatment with antibacterial, antiviral, antifungal, antiparasitic, or antiprotozoal medications within 4 weeks before Screening (Visit 1A), significant viral infections within 4 weeks before Screening (Visit 1A) that may not have been treated with antiviral treatment (eg, influenza receiving only symptomatic treatment).
17. Participants with active autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis.
18. History of malignancy within 5 years before Screening (Visit 1A), except completely treated in situ carcinoma of the cervix, completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin.
19. Previous use of itepekimab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) in former smokers

Secondary endpoints 21

1. Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) in former smokers
2. Change from baseline in post-BD FEV1 in former smokers
3. Change from baseline in pre-BD FEV1 in former smokers
4. Time to first moderate or severe AECOPD in former smokers
5. Annualized rate of severe AECOPD in former smokers
6. Time to first severe AECOPD in former smokers
7. Annualized rate of corticosteroid-treated AECOPD in former smokers
8. Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score in former smokers
9. Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) in former smokers
10. Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score in former smokers
11. Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score in former smokers
12. Incidence of treatment-emergent adverse events (TEAEs), adverse event of special interests (AESIs), serious adverse events (SAEs), and adverse events (AEs) leading to permanent treatment discontinuation in former smokers
13. Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities in former smokers
14. Functional itepekimab concentrations in serum in former smokers
15. Incidence of treatment-emergent anti-itepekimab antibodies responses in former smokers
16. Annualized rate of moderate or severe AECOPD in current smokers
17. Change from baseline in pre-BD FEV1 in current smokers
18. Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation in current smokers
19. Incidence of potentially clinically significant laboratory, vital signs, and ECGs abnormalities in current smokers
20. Functional itepekimab concentrations in serum in current smokers
21. Incidence of treatment-emergent anti-itepekimab antibodies responses in current smokers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 16

Locations

12 EU/EEA countries · 58 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications