Efficacy of Dupilumab Added to Medium Dose Inhaled Corticosteroid/Long-acting Beta-agonist (ICS/LABA) in Comparison to ICS Dose Escalation to High Dose ICS/LABA in Adolescent and Adult Patients with Uncontrolled Asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

11 Mar 2025 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2023-510458-18-00

ClinicalTrials.gov

NCT06572228

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of dupilumab added to medium dose ICS/LABA in reducing severe asthma exacerbations in comparison to ICS dose escalation to high dose ICS-LABA in participants with uncontrolled asthma

Secondary objectives 7

1. To evaluate the effect of dupilumab added to medium dose ICS/LABA vs ICS dose escalation to high dose ICS/LABA on lung function
2. To evaluate the effect of dupilumab added to medium dose ICS/LABA vs escalation to high dose ICS/LABA on annualized cumulative systemic corticosteroid exposure to treat severe asthma exacerbations
3. To evaluate changes in asthma control
4. To evaluate the effect of dupilumab added to medium dose ICS/LABA vs ICS dose escalation to high dose ICS/LABA on additional lung function measurements
5. To compare time to first severe exacerbation event with dupilumab added to medium dose ICS/LABA vs escalation to high dose ICS/LABA
6. To evaluate the proportion of participants achieving an MCID (minimal clinically important difference) in asthma control
7. To evaluate the safety and tolerability of: 1) dupilumab added to medium dose ICS/LABA or 2) high dose ICS/LABA

Conditions and MedDRA coding

Asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participants must be 12 to 80 years of age inclusive at the time of signing the informed consent/assent form with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2023 guidance document
2. Existing treatment with medium dose ICS/LABA (>250 to 500 μg/day of fluticasone propionate DPI (dry powder inhaler) or equivalent, per GINA 2023 guidance document) for at least 3 months with a stable dose ≥1 month prior to visit 1
3. Participants requiring a maximum of 3 controllers for their asthma will be considered eligible for this study
4. Pre-bronchodilator FEV1, as defined in the protocol
5. Reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 μg albuterol/salbutamol at screening OR a documented history of ≥20% reduction in the FEV1, as defined in the protocol
6. Demonstrated adherence to medium dose ICS/LABA on at least 80% of days during the run-in period
7. ACQ-5 score ≥1.5 at screening (visit 1)
8. History of ≥1 severe exacerbation(s) in the previous year before visit 1, but not in the 30 days immediately preceding visit 1
9. Biomarker criteria: Baseline blood eosinophil count ≥300 cells/μL at visit 1 (~90% of population), as defined in the protocol
10. Note: Other protocol-defined Inclusion criteria apply

Exclusion criteria 8

1. Diagnosis of chronic obstructive pulmonary disease (COPD) or other lung diseases which may impair lung function and interfere with treatment assessments
2. Clinical evidence of lung disease(s) other than asthma or imaging (Chest X-ray, computed tomography [CT], magnetic resonance imaging [MRI]) with significant findings within 12 months of visit 1 and up to and including the baseline visit (visit 3)
3. A participant who experiences a severe asthma exacerbation at any time from 1 month prior to the screening visit (visit 1) up to and including the baseline visit (visit 3), as defined in the protocol
4. Weight is less than 30 kilograms
5. Current smoker or cessation of smoking within 6 months prior to visit 1 or previous smoker with a smoking history ≥10 pack-years
6. Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the participant’s participation in the study, as defined in the protocol
7. Participants cannot be on systemic corticosteroids at any time from 1 month prior to the screening visit (visit 1) through the duration of the run-in period
8. Note: Other protocol-defined Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized severe asthma exacerbation rate

Secondary endpoints 14

1. Change in pre-bronchodilator Forced Expiratory Volume in the first second (FEV1)
2. Annualized cumulative dose of systemic corticosteroid exposure to treat severe asthma exacerbations
3. Change in Asthma Control Questionnaire (ACQ-5)
4. Proportion of participants achieving ACQ-5 <1.5
5. Change in pre-bronchodilator FEV1
6. Change in percent of predicted FEV1
7. Change in peak expiratory flow (PEF)
8. Change in forced vital capacity (FVC)
9. Change in forced expiratory flow (FEF) 25-75%
10. Change in FEV1:FVC ratio
11. Change in post-bronchodilator FEV1
12. Time to first severe exacerbation event
13. Proportion of participants achieving a 0.5-point improvement minimal clinically important difference (MCID) in ACQ-5
14. Incidence of Treatment-emergent adverse events (TEAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 11

Locations

3 EU/EEA countries · 20 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 38 files

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

Application history

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