DUPILUMAB for Asthma

Inclusion criteria

• {"criterion_text":"- Participant must be at least 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.\n- Patients with a physician diagnosis of asthma (according to Global Initiative for Asthma (GINA) 2021) for ≥12 months\n- Treatment with medium to high dose inhaled corticosteroids (ICS) in combination with a second controller (eg, long-acting beta-2 adrenergic receptor agonists (LABA), LTRA) with a stable dose ≥1 month prior to Visit 1. Patients requiring a third controller for their asthma will be considered eligible for this study, and it should also be on stable dose ≥1 month prior to Visit 1. Patients requiring an additional controller as a fourth controller (Montelukast) for another type 2 comorbid condition such as allergic rhinitis will be considered eligible for this study, and should be on a stable dose for ≥1 month prior to Visit 1.\n- Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal for adults at Visits 1 and 2, prior to randomization\n- Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.\n- Variable airflow obstruction as documented by one or more of the following (at least 1 needs to be met): i) Positive reversibility test: ≥12% and 200 mL improvement in FEV1 after SABA administration prior to randomization, or documented in the 24 months prior to Visit 1. OR, ii) Positive bronchial challenge test: fall in FEV1 of ≥20% with standard dosis of methacholine, or ≥15% with standardized hyperventilation, hypertonic saline or mannitol challenge prior to randomization or documented in the 24 months prior to Visit 1 OR, iii) Average daily diurnal Peak flow variability of >10% over a 2-week period, documented in the past 24 months prior to Screening Visit 1. OR, iv) Airflow variability in clinic FEV1 >12% and 200 mL between visits outside of respiratory infections, documented in the past 24 months prior to Screening Visit 1. OR v) FEV1 increases by more than 12% and 200mL from baseline after 4 weeks of anti-inflammatory treatment.\n- Reversibility test: Three attempts may be made during the Screening Period until the Baseline visit to meet the qualifying criteria for reversibility. This is only required if reversibility or other evidence of expiratory airflow limitation eligibility criteria was not performed within 24 months prior to Visit 1.\n- FeNO ≥35 ppb at Visit 2, prior to randomization.\n- History of ≥1 severe exacerbation(s) in the previous year before V1 defined as a deterioration of asthma requiring: -- Use of systemic corticosteroids for ≥3 days; or -- Hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids."}

Exclusion criteria

• {"criterion_text":"- History or clinical evidence of chronic obstructive pulmonary disease (COPD) including Asthma-COPD Overlap Syndrome (ACOS) or any other significant lung disease (eg, emphysema, lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome).\n- History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).\n- Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period\n- Current smoker (cigarette or e-cigarette) or cessation of smoking within 6 months prior to Visit 1.\n- Previous smoker with a smoking history >10 pack-years.\n- History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.\n- Any biologic therapy (including experimental treatments and dupilumab) or any other biologic therapy/immunosuppressant/immunomodulators within 4 weeks prior to V1 or 5 half-lives, whichever is longer.\n- Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit) or during the screening period.\n- Severe asthma exacerbation requiring treatment with SCS in the past month before visit 1 or during the screening period.\n- Current acute bronchospasm or status asthmaticus.\n- Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated peripheral eosinophil counts.\n- Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study. Examples include, but are not limited to, participants with short life expectancy, uncontrolled diabetes, cardiovascular conditions, severe renal conditions (eg, participants on dialysis), or other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in the study documents (chart notes, case report forms [CRFs], etc).\n- Patients with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed on a country by country basis, according to local guidelines if required by regulatory authorities or ethics boards, or if TB is suspected by the investigator\n- Known or suspected immunodeficiency, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.\n- Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.\n- Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antifungals or receiving only symptomatic treatment (e.g. influenza or COVID-19) within 2 weeks before the screening visit (Visit 1) or during the screening period."}

Primary endpoints

• {"endpoint_text":"- Rate of change from week 8 to week 52 on post-BD FEV1 slope in FeNO population","definition_or_measurement_approach":"Change in slope of post-bronchodilator forced expiratory volume in 1 second (post-BD FEV1) between week 8 and week 52 in the FeNO population."}

Secondary endpoints

• {"endpoint_text":"- Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population","definition_or_measurement_approach":"Change in slope of post-BD FEV1 between week 8 and week 52 in the total (all randomized) population."}
• {"endpoint_text":"- Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population","definition_or_measurement_approach":"Change in slope of post-BD FEV1 between week 8 and week 104 in the FeNO population."}
• {"endpoint_text":"- Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations","definition_or_measurement_approach":"Absolute change from baseline to week 52 in pre-bronchodilator FEV1 in both FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations","definition_or_measurement_approach":"Absolute change from baseline to week 52 in post-bronchodilator FEV1 in both FeNO and total populations."}
• {"endpoint_text":"- Annualized severe exacerbation rate during the 52-week period in FeNO and Total populations","definition_or_measurement_approach":"Annualized rate of severe asthma exacerbations over the 52-week period in FeNO and total populations (events per patient-year)."}
• {"endpoint_text":"- Change from baseline to week 52 in fractional exhaled nitric oxide (FeNO) levels in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 52 in FeNO levels (ppb) in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 52 in Asthma Control Questionnaire 7 items (ACQ-7) in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 52 in ACQ-7 score in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 52 in pre-BD FEV1 expressed as percent predicted in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 52 in Forced Vital Capacity (FVC) in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 52 in FVC in FeNO and total populations."}
• {"endpoint_text":"- Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population","definition_or_measurement_approach":"Change in slope of post-BD FEV1 between week 8 and week 104 in the total population."}
• {"endpoint_text":"- Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in pre-BD FEV1 in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in post-BD FEV1 in FeNO and total populations."}
• {"endpoint_text":"- Annualized severe exacerbation rate during the 104-week period in FeNO and Total populations","definition_or_measurement_approach":"Annualized rate of severe exacerbations over 104 weeks in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 in FeNO levels in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in FeNO levels (ppb) in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 in ACQ-7 in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in ACQ-7 score in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in pre-BD FEV1 percent predicted in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 FVC in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in FVC in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 52 in Asthma Quality Of Life Questionnaire with Standardized Activities (AQLQ(S)) in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 52 in AQLQ(S) score in FeNO and total populations."}
• {"endpoint_text":"- Change from baseline to week 104 in AQLQ(S) in FeNO and Total populations","definition_or_measurement_approach":"Change from baseline to week 104 in AQLQ(S) score in FeNO and total populations."}
• {"endpoint_text":"- Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations","definition_or_measurement_approach":"Change in slope of post-BD FEV1 between week 8 and week 156 in FeNO and total populations."}
• {"endpoint_text":"- Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)","definition_or_measurement_approach":"Incidence and counts of TEAEs and SAEs reported during the study period."}
• {"endpoint_text":"- Incidence of adverse events of special interest (AESIs)","definition_or_measurement_approach":"Incidence and counts of predefined AESIs during the study."}

Belgium

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

15-07-2024

Processing Time Days

11

Number Of Sites

2

Number Of Participants

43

Bulgaria

Earliest CTIS Part Ii Submission Date

17-07-2024

Latest Decision Or Authorization Date

18-07-2024

Processing Time Days

1

Number Of Sites

8

Number Of Participants

90

Ireland

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

09-07-2024

Processing Time Days

5

Number Of Sites

2

Number Of Participants

14

Hungary

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

09-07-2024

Processing Time Days

5

Number Of Sites

10

Number Of Participants

94

Slovakia

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

10-07-2024

Processing Time Days

6

Number Of Sites

5

Number Of Participants

100

Greece

Earliest CTIS Part Ii Submission Date

29-08-2024

Latest Decision Or Authorization Date

25-09-2024

Processing Time Days

27

Number Of Sites

11

Number Of Participants

80

Romania

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

11-07-2024

Processing Time Days

7

Number Of Sites

10

Number Of Participants

85

Primary sponsor

Full Name

Sanofi-Aventis Recherche & Developpement

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Endpoint Clinical Inc.

Responsibilities

sponsorDuties code: 3 (as listed)

Name

Eresearchtechnology Inc.

Responsibilities

sponsorDuties codes/values: 15 (G&L SP), 7

Name

Pharmaceutical Product Development LLC

Responsibilities

sponsorDuties code: 4

Name

ESMS Global Limited

Responsibilities

sponsorDuties: 15 (Centralized 24-Hour Emergency System: eSMS)

Third parties

• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"sponsorDuties codes: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes/values: 15 (G&L SP), 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"ESMS Global Limited","duties_or_roles":"sponsorDuties: 15 (Centralized 24-Hour Emergency System: eSMS)","organisation_type":"Pharmaceutical company"}