Study Assessing the Long-term Effect of Dupilumab on Prevention of Lung Function Decline in Adult Patients with Uncontrolled Moderate to Severe Asthma

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

25 Aug 2022 → ongoing

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513423-16-00

EudraCT number

2021-003903-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

In a population with moderate-to-severe asthma:
To assess the effect of dupilumab on preventing or slowing the rate of lung function decline by week 52 (year 1) compared to placebo in the FeNO population

Secondary objectives 7

1. To evaluate the long-term effect of dupilumab on preventing or slowing the rate of lung function decline by week 52 (year 1) compared to placebo in total population
2. To evaluate the long-term effect of dupilumab on preventing or slowing the rate of lung function decline by week 104 (year 2) compared to placebo in FeNO population
3. To evaluate the effect of dupilumab on improving lung function parameters, exacerbations, asthma control and biomarker levels at week 52 compared to placebo in FeNO and total populations
4. To evaluate the long-term effect of dupilumab on improving lung function parameters, exacerbations, asthma control and biomarker levels at week 104 compared to placebo in FeNO and total populations
5. To evaluate the long-term effect of dupilumab in improving quality of life at week 52 and 104 compared to placebo in FeNO and total populations
6. To evaluate the long-term effect of dupilumab on preventing or slowing the rate of lung function decline by week 156 (year 3) compared to placebo in FeNO and total populations
7. To evaluate the safety of dupilumab

Conditions and MedDRA coding

Asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 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.
2. Patients with a physician diagnosis of asthma (according to Global Initiative for Asthma (GINA) 2021) for ≥12 months
3. 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.
4. Pre-bronchodilator forced expiratory volume (FEV1) ≤ 80% of predicted normal for adults at Visits 1 and 2, prior to randomization
5. Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 and 2, prior to randomization.
6. 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.
7. 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.
8. FeNO ≥35 ppb at Visit 2, prior to randomization.
9. 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 16

1. 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).
2. Severe asthma exacerbation requiring treatment with SCS in the past month before visit 1 or during the screening period.
3. Current acute bronchospasm or status asthmaticus.
4. Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated peripheral eosinophil counts.
5. 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).
6. 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
7. 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.
8. 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.
9. 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.
10. History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).
11. 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
12. Current smoker (cigarette or e-cigarette) or cessation of smoking within 6 months prior to Visit 1.
13. Previous smoker with a smoking history >10 pack-years.
14. History of systemic hypersensitivity or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.
15. 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.
16. Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit) or during the screening period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of change from week 8 to week 52 on post-BD FEV1 slope in FeNO population

Secondary endpoints 22

1. Rate of change from week 8 to week 52 on post-BD FEV1 slope in the Total population
2. Rate of change from week 8 to week 104 on post-BD FEV1 slope in the FeNO population
3. Change from baseline to week 52 in pre-BD FEV1 in FeNO and Total populations
4. Change from baseline to week 52 in post-BD FEV1 in FeNO and Total populations
5. Annualized severe exacerbation rate during the 52-week period in FeNO and Total populations
6. Change from baseline to week 52 in fractional exhaled nitric oxide (FeNO) levels in FeNO and Total populations
7. Change from baseline to week 52 in Asthma Control Questionnaire 7 items (ACQ-7) in FeNO and Total populations
8. Change from baseline to week 52 in pre-BD FEV1 % predicted in FeNO and Total populations
9. Change from baseline to week 52 in Forced Vital Capacity (FVC) in FeNO and Total populations
10. Rate of change from week 8 to week 104 on post-BD FEV1 slope in Total Population
11. Change from baseline to week 104 in pre-BD FEV1 in FeNO and Total populations
12. Change from baseline to week 104 in post-BD FEV1 in FeNO and Total populations
13. Annualized severe exacerbation rate during the 104-week period in FeNO and Total populations
14. Change from baseline to week 104 in FeNO levels in FeNO and Total populations
15. Change from baseline to week 104 in ACQ-7 in FeNO and Total populations
16. Change from baseline to week 104 in pre-BD FEV1 % predicted in FeNO and Total populations
17. Change from baseline to week 104 FVC in FeNO and Total populations
18. Change from baseline to week 52 in Asthma Quality Of Life Questionnaire with Standardized Activities (AQLQ(S)) in FeNO and Total populations
19. Change from baseline to week 104 in AQLQ(S) in FeNO and Total populations
20. Rate of change from week 8 to week 156 on post-BD FEV1 slope in FeNO and Total populations
21. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
22. Incidence of adverse events of special interest (AESIs)

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 4

Locations

7 EU/EEA countries · 47 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 44 files

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

Application history

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