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

Phase 3
Active, not recruiting
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Registration Number
NCT04751487
Lead Sponsor
Sanofi
Brief Summary

Primary Objective:

Primary population (former smokers cohort):

* 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:

Primary population (former smokers cohort):

* 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

Secondary population (current smokers cohort)

* 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

* Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD

* Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD

* Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD

* Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD

Detailed Description

The study duration per participant:

* Screening period is 3-5 weeks

* Randomized investigational medicinal product (IMP) treatment period is 52 weeks for first cohort of randomized former smoker participants \[approximately 930\] and cohort of current smokers \[approximately 280\], and 24 to 52 weeks for potential additional randomized former smoker participants

* Post-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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
1239
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Itepekimab Q4W in former smokersItepekimab SAR440340SC 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
Itepekimab Q4W in former smokersPlaceboSC 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
Placebo in former smokersPlaceboSC administration of matching placebo Q2W for up to 52 weeks
Itepekimab Q2W in current smokersItepekimab SAR440340SC administration of Itepekimab every 2 weeks (Q2W) for 52 weeks
Placebo in current smokersPlaceboSC administration of matching placebo Q2W for 52 weeks
Itepekimab Q2W in former smokersItepekimab SAR440340Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks
Primary Outcome Measures
NameTimeMethod
Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) in former smokersBaseline up to End Of Treatment (EOT) (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)

Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) over the placebo-controlled treatment period.

Secondary Outcome Measures
NameTimeMethod
Change from baseline in pre-BD FEV1 in former smokersBaseline to Week 52

FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer.

Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score in former smokersBaseline 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.

Change from baseline in post-BD FEV1 in former smokersBaseline 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 St. George's Respiratory Questionnaire (SGRQ) total score in former smokersBaseline 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 potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities in former smokersBaseline 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)
Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) in former smokersBaseline 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 in former smokersBaseline through EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)

Time to first moderate or severe AECOPD over the placebo-controlled treatment period.

Change from baseline in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total score in former smokersBaseline 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.

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 smokersBaseline 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)
Functional itepekimab concentrations in serum in former smokersBaseline 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)
Annualized rate of severe AECOPD in former smokersBaseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)

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

Time to first severe AECOPD in former smokersBaseline through EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)

Time to first severe AECOPD over the placebo-controlled treatment period.

Annualized rate of corticosteroid-treated AECOPD in former smokersBaseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)

Annualized rate of corticosteroid-treated AECOPD over the placebo-controlled treatment period.

Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) in former smokersBaseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants)
Incidence of treatment-emergent anti-itepekimab antibodies responses in former smokersBaseline 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 in current smokersBaseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Incidence of potentially clinically significant laboratory, vital signs, and ECGs abnormalities in current smokersBaseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Change from baseline in pre-BD FEV1 in current smokersBaseline up 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.

Incidence of treatment-emergent anti-itepekimab antibodies responses in current smokersBaseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)
Annualized rate of moderate or severe AECOPD in current smokersBaseline up to Week 52

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

Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation in current smokersBaseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133)

Trial Locations

Locations (297)

Synexus Phoenix Central (Central Phoenix Medical Clinic)- Site Number : 8400333

🇺🇸

Phoenix, Arizona, United States

UCSF Fresno - Site Number : 8400030

🇺🇸

Fresno, California, United States

Palmtree Clinical Research Site Number : 8400184

🇺🇸

Palm Springs, California, United States

Allianz Research Institute Colorado Site Number : 8400061

🇺🇸

Denver, Colorado, United States

Helix Biomedics, LLC - Site Number : 8400049

🇺🇸

Boynton Beach, Florida, United States

Innovative Research of West Florida, Inc- Site Number : 8400041

🇺🇸

Clearwater, Florida, United States

Beautiful Minds Clinical Research Center Site Number : 8400352

🇺🇸

Cutler Bay, Florida, United States

Omega Research - Site Number : 8400031

🇺🇸

DeBary, Florida, United States

Sciences Connections, LLC Site Number : 8400045

🇺🇸

Doral, Florida, United States

North Florida/South Georgia Veterans Health System Site Number : 8400176

🇺🇸

Gainesville, Florida, United States

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Synexus Phoenix Central (Central Phoenix Medical Clinic)- Site Number : 8400333
🇺🇸Phoenix, Arizona, United States

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