Efficacy and safety of subcutaneous dupilumab in participants with asthma/asthmatic wheeze aged 2 to <6 years

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Research & Development

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

2 Aug 2024 → ongoing

Decision date (initial)

2023-12-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Research & Development

External identifiers

EU CT number

2023-504331-41-00

WHO UTN

U1111-1246-7432

ClinicalTrials.gov

NCT06191315

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety

• Part A: To assess the efficacy of dupilumab in reducing the annualized rate of severe asthma exacerbations at Week 52 compared to placebo
• Part B: Safety and tolerability of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic during Part B

Secondary objectives 13

1. Part A: To assess the efficacy of dupilumab in decreasing the need of hospitalization/ ER or urgent care visit at Week 52 compared to placebo
2. Part A: To assess the efficacy of dupilumab in decreasing the need for increased inhaled corticosteroid (ICS) dose compared to placebo
3. Part A: To assess the efficacy of dupilumab in decreasing the need of reliever use compared to placebo
4. Part A: To evaluate the efficacy of dupilumab in improving asthma symptoms compared to placebo
5. Part A: To assess the safety and tolerability of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze compared to placebo
6. Part A: To assess the effect of dupilumab to improve the health-related quality of life (HRQoL), global impression of asthma severity and control (from caregiver’s and from clinician’s perspective) for children with uncontrolled asthma and/or recurrent severe asthmatic wheeze compared to placebo
7. Part A: To explore baseline and on-treatment levels of biomarker for their potential to predict and to associate with a treatment response
8. Part A: To evaluate the pharmacokinetics (PK) of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze compared to placebo
9. Part A: To assess the immunogenicity to dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze compared to placebo
10. Part A: To evaluate the association between dupilumab treatment and immune response to non-live vaccines among children aged 2 to <6 years with uncontrolled asthma and/or recurrent severe asthmatic wheeze compared to placebo
11. Part B: To evaluate the efficacy of dupilumab in reducing the annualized rate of severe asthma exacerbations compared to placebo
12. Part B: To evaluate the pharmacokinetics (PK) of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze
13. Part B: To assess the immunogenicity to dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze

Conditions and MedDRA coding

Respiratory tract diseases - Wheezing, Asthma

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001501-PIP02-08

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysys plan and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting can be found at: https://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Participant must be 2 to <6 years of age
2. Diagnosis of asthma or recurrent severe asthmatic wheeze that is not controlled with chronic ICS for at least 3 months with stable use of at least low dose ICS for ≥1 month prior to Screening Visit 1 with evidence of uncontrolled asthma and/or recurrent severe asthmatic wheeze.
3. At least one additional major criterion from the modified asthma predictive index: a) Physician diagnosed Atopic Dermatitis, b) Allergic sensitization to at least 1 aeroallergen (with a positive serum IgE defined as a value ≥0.35 kU/L). OR 2 minor critieria: c) Wheezing unrelated to colds, d) Peripheral blood eosinophilia ≥4%, e) Allergic sensitization to milk, eggs, or peanuts (defined by serum specific IgE >0.35 kU/L.
4. Parent(s)/caregiver(s)/legal guardian(s) willing and able to comply with clinic visits and study-related procedures.
5. Parent(s)/caregiver(s)/legal guardian(s) able to understand the study requirements.
6. Participants/parent(s)/caregiver(s)/legal guardian(s), as appropriate, must be able to understand and complete study-related questionnaires
7. Body weight at screening and randomization >5 kg and <30 kg.
8. Parents or caregivers or legal guardian capable of giving signed informed consent.

Exclusion criteria 5

1. Severe asthma with the need for chronic oral/systemic corticosteroid use (>1 month continuous) at the time of screening enrollment.
2. History of a systemic hypersensitivity reaction or anaphylaxis to biologic therapy, including any excipient.
3. History of prematurity (<34 weeks gestation).
4. Any other chronic lung disease that would impair lung function (eg, cystic fibrosis, bronchopulmonary dysplasia) or chronic lung disease of prematurity or need for oxygen for more than 5 days in the neonatal period.
5. History of life-threatening asthma (eg, requiring intubation).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period.
2. Part B: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and AEs leading to permanent treatment discontinuation

Secondary endpoints 21

1. Part A: Annualized rate of hospitalization, ER or urgent care visit for asthma exacerbation during the 52 week treatment period.
2. Part A: Annualized rate of moderate asthma exacerbations during the 52-week treatment period
3. Part A: Cumulative ICS dose during the 52-week treatment period
4. Part A: Change from baseline in weekly average use of reliever medication during the 52-week treatment period
5. Part A: Mean number of days without asthma symptoms (DWAS) using the Pediatric Asthma Caregiver Diary (PACD) during the 52-week treatment period
6. Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD
7. Part A: Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation
8. Part A: Change from baseline to Week 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale
9. Part A: Caregiver Global Impression of Change in their child’s asthma control (CGI-change in asthma control) at Week 52
10. Part A: Physician Global Assessment of Change of the child’s asthma control (PGA-change in asthma control) at Week 52
11. Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child’s asthma control (CGI-asthma control)
12. Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child’s asthma severity (CGI-asthma severity)
13. Part A: Change from baseline to Week 52 in Physician Global Assessment of the child’s asthma control (PGA-asthma control).
14. Part A: Change from baseline to Week 52 in Test for Respiratory and Asthma Control in Kids (TRACK)
15. Part A: Change from baseline in blood eosinophil level at Weeks 24 and 52
16. Part A: Concentration of dupilumab in serum over time during the 52-week treatment period
17. Part A: Incidence of treatment-emergent anti-drug antibody (ADA) against dupilumab over time
18. Part A: IgG response to any vaccination for tetanus, diphtheria and pertussis and antibody for influenza (HAI antibody titers) vaccine administered according to vaccination schedule during the 52-week treatment period
19. Part B: Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period
20. Part B Concentration of dupilumab in serum over time during the 52-week Part B treatment period
21. Part B: Incidence of treatment-emergent anti-drug antibodies (ADAs) against dupilumab over time

Investigational products

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

Test 2

Placebo 2

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Research & Development

Sponsor organisation

Sanofi-Aventis Research & Development

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 11

Locations

9 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 97 files

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

Application history

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