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

JRCT ID: jRCT2071210004

Registered date:06/04/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Chronic Obstructive Pulmonary Disease
• Date of first enrollment: 05/04/2021
• Target sample size: 1210
• Countries of recruitment: Canada,Japan,United States,Japan,Argentina,Japan,Brazil,Japan,Bulgaria,Japan,Chile,Japan,Czechia,Japan,Denmark,Japan,France,Japan,Germany,Japan,Hungary,Japan,Israel,Japan,Republic of Korea,Japan,Mexico,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,Puerto Rico,Japan,Russian Federation,Japan,South Africa,Japan,Spain,Japan,Turkey,Japan,United Kingdom,Japan,Estonia,Japan,Georgia,Japan,India,Japan,Latvia,Japan,Lithuania,Japan
• Study type: Interventional

Intervention(s)

Drug: Itepekimab SAR440340 (REGN3500)
Pharmaceutical form: solution for injection in pre-filled syringe
Route of administration: Subcutaneous
Drug: Placebo
Pharmaceutical form: solution for injection in pre-filled syringe
Route of administration: Subcutaneous

Arms
- Experimental: Itepekimab Q2W in former smokers
Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks
- Experimental: Itepekimab Q4W in former smokers
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
- Placebo Comparator: Placebo in former smokers
SC administration of matching placebo Q2W for up to 52 weeks
- Experimental: Itepekimab Q2W in current smokers
SC administration of Itepekimab every 2 weeks (Q2W) for 52 weeks
- Placebo Comparator: Placebo in current smokers
SC administration of matching placebo Q2W for 52 weeks

Outcome(s)

Primary Outcome

1. Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) in former smokers [ Time Frame: Baseline 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 52-week placebo-controlled treatment period.

Secondary Outcome

1. Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) in former smokers [ 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.

2. Change from baseline in post-BD FEV1 in former smokers [ 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.

3. Change from baseline in pre-BD FEV1 in former smokers [ 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.

4. Time to first moderate or severe AECOPD in former smokers [ Time Frame: Baseline 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.

5. Annualized rate of severe AECOPD in former smokers [ Time Frame: Baseline 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.

6. Time to first severe AECOPD in former smokers [ Time Frame: Baseline 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.

7. Annualized rate of corticosteroid-treated AECOPD in former smokers [ Time Frame: Baseline 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.

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

9. Rate of change in post-BD FEV1 (L) from baseline (post-BD FEV1 slope) in former smokers [ Time Frame: Baseline up to EOT (Week 52 for initial randomized participants, 24 to 52 weeks for potential additional randomized former smoker participants) ]

10. Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score in former smokers [ 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.

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

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 [ 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) ]

13. Incidence of potentially clinically significant laboratory test, vital signs, and electrocardiogram (ECGs) abnormalities in former smokers [ 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) ]

14. Functional itepekimab concentrations in serum in former smokers [ 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) ]

15. Incidence of treatment-emergent anti-itepekimab antibodies responses in former smokers [ 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) ]

16. Annualized rate of moderate or severe AECOPD in current smokers [ Time Frame: Baseline up to Week 52 ]
Annualized rate of moderate or severe AECOPD over the placebo-controlled treatment period.

17. Change from baseline in pre-BD FEV1 in current smokers [ Time Frame: Baseline 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.

18. Incidence of TEAEs, AESIs, SAEs, and AEs leading to permanent treatment discontinuation in current smokers [ Time Frame: Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133) ]

19. Incidence of potentially clinically significant laboratory, vital signs, and ECGs abnormalities in current smokers [ Time Frame: Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133) ]

20. Functional itepekimab concentrations in serum in current smokers [ Time Frame: Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133) ]

21. Incidence of treatment-emergent anti-itepekimab antibodies responses in current smokers [ Time Frame: Baseline up to EOS (Week 72 for participants not transitioning to the extension study LTS18133; Week 52 for participants transitioning to the extension study LTS18133) ]

Key inclusion & exclusion criteria

• Age minimum: >= 40age old
• Age maximum: <= 85age old
• Gender: Both

Include 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:
- - 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.
- 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.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- 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.
- For former smokers: Active smoking or vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within 6 months prior to Screening (Visit 1A).
For current smokers: vaping of any products (eg, nicotine, 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 alpha-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-Guerin (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 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.
- 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT04751487,2020-001819-24,2024-512012-21