Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (AERIFY-1)

• ClinicalTrials.gov Identifier: NCT04701983
• Recruitment Status: Recruiting
• First Posted: January 8, 2021
• Last Update Posted: May 10, 2024
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: December 30, 2020
• First Posted Date: January 8, 2021
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: December 16, 2020
• Estimated Primary Completion Date: June 27, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2022)

Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) [ Time Frame: Baseline up to End Of Treatment (EOT) (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]

Annualized rate of moderate or severe AECOPD over the placebo-controlled treatment period

Original Primary Outcome Measures (submitted: January 6, 2021)

Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) [ Time Frame: Baseline up to Week 52 ]

Annualized rate of moderate or severe AECOPD over the 52-week placebo-controlled treatment period

Current Secondary Outcome Measures (submitted: November 27, 2023)

• Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline to Week 24 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in post-BD FEV1 [ Time Frame: Baseline to Week 24 and Week 52 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in pre-BD FEV1 [ Time Frame: Baseline to Week 52 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Time to first moderate or severe AECOPD [ Time Frame: Baseline through EOT (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]
  Time to first moderate or severe AECOPD over the placebo-controlled treatment period
• Annualized rate of severe AECOPD [ Time Frame: Baseline up to EOT (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]
  Annualized rate of severe AECOPD over the placebo-controlled treatment period
• Time to first severe AECOPD [ Time Frame: Baseline through EOT (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]
  Time to first severe AECOPD over the placebo-controlled treatment period.
• Annualized rate of corticosteroid-treated AECOPD [ Time Frame: Baseline up to EOT (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]
  Annualized rate of corticosteroid-treated AECOPD over the placebo-controlled treatment period.
• Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score [ Time Frame: Baseline to Week 24 and Week 52 ]
  The E-RS: COPD is administered as a part of the 14-item EXACT questionnaire and is completed on a daily basis.The 11-item E-RS:COPD assesses severity of respiratory symptoms overall and severity of individual symptoms such as breathlessness, cough and sputum, and chest symptoms The total score of E-RS:COPD ranges from 0 to 40, with higher values indicating more severe respiratory symptoms.
• Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) [ Time Frame: Baseline up to EOT (Week 52 for initial randomized participants, Week 24 to 52 for potential additional randomized participants) ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in St. George''s Respiratory Questionnaire (SGRQ) total score [ Time Frame: Baseline to Week 24 and Week 52 ]
  The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
• Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score [ Time Frame: Baseline to Week 24 and Week 52 ]
  The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
• 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 [ Time Frame: Baseline up to End-of-Study (EOS) (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133) ]
• Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities [ Time Frame: Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133) ]
• Functional itepekimab concentrations in serum [ Time Frame: Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133) ]
• Incidence of treatment-emergent anti-itepekimab antibodies responses [ Time Frame: Baseline up to EOS (Up to Week 72 for participants not transitioning to the extension study LTS18133; Up to Week 52 for participants transitioning to the extension study LTS18133) ]

Original Secondary Outcome Measures (submitted: January 6, 2021)

• Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at Week 52 [ Time Frame: Baseline to Week 52 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in post-BD FEV1 at Week 52 [ Time Frame: Baseline to Week 52 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in pre-BD FEV1 at Week 24 [ Time Frame: Baseline to Week 24 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Time to first moderate or severe AECOPD [ Time Frame: Baseline through Week 52 ]
  Time to first moderate or severe AECOPD over the 52 week placebo-controlled treatment period.
• Annualized rate of severe AECOPD [ Time Frame: Baseline up to Week 52 ]
  Annualized rate of severe AECOPD over the 52 week placebo-controlled treatment period.
• Time to first severe AECOPD [ Time Frame: Baseline through Week 52 ]
  Time to first severe AECOPD over the 52-week placebo-controlled treatment period.
• Annualized rate of corticosteroid-treated AECOPD [ Time Frame: Baseline up to Week 52 ]
  Annualized rate of corticosteroid-treated AECOPD over the 52-week placebo-controlled treatment period.
• Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score at Week 52 [ Time Frame: Baseline to Week 52 ]
  The E-RS: COPD is administered as a part of the 14-item EXACT questionnaire and is completed on a daily basis.The 11-item E-RS:COPD assesses severity of respiratory symptoms overall and severity of individual symptoms such as breathlessness, cough and sputum, and chest symptoms The total score of E-RS:COPD ranges from 0 to 40, with higher values indicating more severe respiratory symptoms.
• Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) [ Time Frame: Baseline up to Week 52 ]
  FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.
• Change from baseline in St. George''s Respiratory Questionnaire (SGRQ) total score at Week 52 [ Time Frame: Baseline to Week 52 ]
  The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
• Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 52 [ Time Frame: Baseline to Week 52 ]
  The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life.
• 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 [ Time Frame: Baseline up to end of study (Week 72) ]
• Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities [ Time Frame: Baseline up to end of study (Week 72) ]
• Functional itepekimab concentrations in serum [ Time Frame: Baseline up to end of study (Week 72) ]
• Incidence of treatment-emergent anti-itepekimab antibodies responses [ Time Frame: Baseline up to end of study (Week 72) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab in Chronic Obstructive Pulmonary Disease (COPD)
• Official Title: Randomized, Double-blind, Placebo-controlled, Parallel Group Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD)

Brief Summary

Primary Objective:

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:

• Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD
• Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD
• Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD
• Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD
• Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD
• 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
• 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
• Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD
• Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD
• Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPD

Detailed Description

The study duration per participant:

• Screening period is 3-5 weeks
• Placebo-controlled treatment period is 52 weeks for first approximately 960 randomized participants, and 24 to 52 weeks for potential additional randomized participants
• Post-investigational medicinal product (IMP) treatment follow-up period is 20 weeks for participants not transitioning to the extension study LTS18133 Note: A long-term, double-blinded extension study (LTS18133) will be implemented to allow participants in this study to continue receiving active IMP for an additional period. Only participants completing their End-of-Treatment (EOT) visit per this study protocol will be offered to participate in the LTS18133 study.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Obstructive Pulmonary Disease

Intervention

• Drug: Itepekimab SAR440340
  Pharmaceutical form: solution for injection in pre-filled syringe Route of administration: subcutaneous
  Other Name: REGN3500
• Drug: Placebo
  Pharmaceutical form: solution for injection in pre-filled syringe Route of administration: subcutaneous

Study Arms

• Experimental: Itepekimab Q2W
  Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks
  Intervention: Drug: Itepekimab SAR440340
• Experimental: Itepekimab Q4W
  SC administration of Itepekimab every 4 weeks (Q4W) for up to 52 weeks, with alternating SC administration of matching placebo at the 2-week interval between active IMP
  Interventions:

  • Drug: Itepekimab SAR440340
  • Drug: Placebo
• Placebo Comparator: Placebo
  SC administration of matching placebo Q2W for up to 52 weeks
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 28, 2022): 960
• Original Estimated Enrollment (submitted: January 6, 2021): 930
• Estimated Study Completion Date: November 28, 2025
• Estimated Primary Completion Date: June 27, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria :

• Participant must be 40 to 85 years of age inclusive.
• Physician diagnosis of COPD for at least 1 year (based on Global Initiative for Chronic Obstructive Lung Disease [GOLD] definition).
• Smoking history of ≥10 pack-years, but who are not currently smoking, and smoking cessation must have occurred ≥6 months prior to Screening (Visit 1A) with an intention to quit permanently.
• Participants with moderate-to-severe COPD
• 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).

• 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.
• 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.
• Body mass index (BMI) ≥18.0 kg/m^2, or BMI ≥16.0 kg/m^2 for participants enrolled in East-Asian countries.

• 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:

• 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.
• Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
• 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.
• 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.
• Diagnosis of cor pulmonale, evidence of right cardiac failure, or moderate-to-severe pulmonary hypertension.
• Hypercapnia requiring bilevel positive airway pressure (BiPAP).
• Moderate or severe exacerbation of COPD (AECOPD) within 4 weeks prior to Screening (Visit 1A).
• 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.
• 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).
• Cardiac arrhythmias including paroxysmal (eg, intermittent) atrial fibrillation.
• Uncontrolled hypertension (ie, systolic blood pressure [BP] >180 mm Hg or diastolic BP >110 mm Hg with or without use of anti-hypertensive 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 received Bacillus Calmette-Guérin (BCG)-vaccination within 12 weeks prior to Screening (Visit 1A).
• History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Screening (Visit 1A).
• 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 sScreening (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.
• 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).
• 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.
• 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.
• Previous use of itepekimab.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; contact-us@sanofi.com

• Listed Location Countries: Argentina, Bulgaria, Chile, China, Czechia, Georgia, Greece, Hungary, India, Israel, Italy, Mauritius, Mexico, Poland, Romania, Russian Federation, Slovakia, Taiwan, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04701983
• Other Study ID Numbers: EFC16750; U1111-1250-2787 ( Registry Identifier: ICTRP ); 2024-512013-41 ( Registry Identifier: CTIS ); 2020-001818-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: May 2024