Efficacy and Safety of Subcutaneous Dupilumab in Participants With Asthma/Asthmatic Wheeze Aged 2 to <6 Years (LIBERTY ASTHMA TREKIDS)

Asthma Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Longterm Safety of Dupilumab in Children 2 to <6 Years of Age With Uncontrolled Asthma and/or Recurrent Severe Asthmatic Wheeze

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06191315
• Other study ID #: EFC14771
• Secondary ID: 2023-504331-41U1
• Status: Recruiting
• Phase: Phase 3
• Start date: January 3, 2024
• Est. completion date: December 21, 2028

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a parallel, Phase 3, 2-arm study to evaluate the efficacy and long-term safety of dupilumab treatment in children 2 to <6 years of age with uncontrolled asthma and/or recurrent severe asthmatic wheeze. The study will be conducted in 2 parts. Part A will be a 52-week, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of dupilumab in children aged 2 to <6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze. At the end of Part A, all eligible participants will be offered participation in Part B, an optional open-label extension phase.

Study details include:

Part A:

The study duration of part A will be up to 68 weeks consisting of a 4-week Screening, a 52week treatment period, and a 12-week post-treatment follow-up period. For participants who will chose to participate in Part B, the study duration will be up to 120 weeks (additional 52-week treatment period).

Part B:

For participants who will choose to participate in Part B, the study duration will be up to 120 weeks (Part A [4-week Screening and a 52-week treatment period] plus additional 52-week treatment period and a 12-week post-treatment follow-up period).

Description:

The duration per participant is up to 120 Weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 21, 2028
• Est. primary completion date: December 21, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 5 Years

Eligibility

Inclusion Criteria:

• Participant must be 2 to <6 years of age

• 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*.

• At least one additional major criterion from the modified asthma predictive index:

1. Physician diagnosed Atopic Dermatitis,

2. Allergic sensitization to at least 1 aeroallergen (with a positive serum IgE defined as a value =0.35 kU/L).

OR 2 minor criteria:

3. Wheezing unrelated to colds,

4. Peripheral blood eosinophilia =4%,

5. Allergic sensitization to milk, eggs, or peanuts (defined by serum specific IgE >0.35 kU/L.

• Parent(s)/caregiver(s)/legal guardian(s) willing and able to comply with clinic visits and study-related procedures.

• Parent(s)/caregiver(s)/legal guardian(s) able to understand the study requirements.

• Participants/parent(s)/caregiver(s)/legal guardian(s), as appropriate, must be able to understand and complete study-related questionnaires

• Body weight at screening and randomization >5 kg and <30 kg.

• Parents or caregivers or legal guardian capable of giving signed informed consent.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Severe asthma with the need for chronic oral/systemic corticosteroid use (>1 month continuous) at the time of screening enrollment.

• History of a systemic hypersensitivity reaction or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.

• History of prematurity (<34 weeks gestation).

• 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.

• History of life-threatening asthma (eg, requiring intubation).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Asthma
• Respiratory Sounds
• Wheezing

Intervention

Drug:
• Dupilumab
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320002	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320003	Ciudad Autonoma Bs As
Argentina	Investigational Site Number : 0320001	Ciudad Autonoma Buenos Aires
Argentina	Investigational Site Number : 0320004	Mendoza
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Brazil	Hospital Ernesto Dornelles Site Number : 0760004	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de Medicina Integral Prof Fernando Figueira Site Number : 0760006	Recife	Pernambuco
Brazil	Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo Site Number : 0760001	São Paulo
Brazil	Clinica de Alergia Martti Antila Site Number : 0760002	Sorocaba	São Paulo
Canada	Investigational Site Number : 1240007	Hamilton	Ontario
United Kingdom	Investigational Site Number : 8260001	London
United States	TTS Research Site Number : 8400022	Boerne	Texas
United States	UBMD Pediatrics, Oishei Childrens Hospital Site Number : 8400013	Buffalo	New York
United States	Allervie Health - Destin (AllerVie Clinical Research) Site Number : 8400016	Destin	Florida
United States	Newport Childrens Medical Group Site Number : 8400023	Newport Beach	California
United States	Allergy & Asthma Specialists, PSC Site Number : 8400002	Owensboro	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period	Annualized rate of severe asthma exacerbations during the 52-week treatment period.	Baseline through Week 52
Primary	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	Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation.	Week 52 through Week 116
Secondary	Part A: Annualized rate of hospitalization, ER or urgent care visit for asthma exacerbation during the 52week treatment period.		Baseline through Week 52
Secondary	Part A: Annualized rate of moderate asthma exacerbations during the 52-week treatment period	Annualized rate of moderate asthma exacerbations during the 52-week treatment period.	Baseline through Week 52
Secondary	Part A: Cumulative ICS dose during the 52-week treatment period		Baseline through Week 52
Secondary	Part A: Change from baseline in weekly average use of reliever medication during the 52-week treatment period		Baseline to Week 52
Secondary	Part A: Mean number of days without asthma symptoms (DWAS) using the Pediatric Asthma Caregiver Diary (PACD) during the 52-week treatment period	A day without asthma symptoms (DWAS) is defined as a day without any asthma symptoms, ß-agonist use, oral steroid use, or need for urgent asthma care. The PACD consists of a daytime and overnight record. The daytime asthma symptom questions are scored on a 6-point scale from 0 (no symptoms/interference) to 5 (very severe symptoms/interference). The overnight questions are scored on a 5-point scale from 0 (no overnight cough and caregiver not disturbed at all) to 4 (coughed all night and disturbed all night).	Baseline through Week 52
Secondary	Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD	The PACD consists of a daytime and overnight record. The daytime asthma symptom questions are scored on a 6-point scale from 0 (no symptoms/interference) to 5 (very severe symptoms/interference).	Baseline to Week 52
Secondary	Part A: Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation		Baseline through Week 52
Secondary	Part A: Change from baseline to Week 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale	PedsQL measures health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Scores range 0-100 with higher scores indicate better HRQOL.	Baseline to Week 52
Secondary	Part A: Caregiver Global Impression of Change in their child's asthma control (CGI-change in asthma control) at Week 52	CGI-change in asthma control is a 1-item questionnaire that asks the caregiver to provide the overall assessment of change of their child's asthma control on a 7-point scale, compared to just before he/she started taking the study treatment. Response choices are: 0 = "Very much better", 1 ="Moderately better", 2 = "A little better", 3 = "No change", 4 = "A little worse", 5 = "Moderately worse", 6 = "Very much worse".	Week 52
Secondary	Part A: Physician Global Assessment of Change of the child's asthma control (PGA-change in asthma control) at Week 52	The Physician Global Assessment of Change of Asthma (PGA-change in asthma control) is a 1 item questionnaire that asks the physician to provide the overall assessment of change in the child's asthma control on a 7-point scale, compared to just before he/she started taking the study treatment. Response choices are: 0 = "Very much better", 1 = "Moderately better", 2 ="A little better", 3 = "No change", 4 = "A little worse", 5 = "Moderately worse", 6 = "Very much worse".	Week 52
Secondary	Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma control (CGI-asthma control)	The Caregiver Global Impression of asthma control (CGI-Asthma Control) is a 1-item questionnaire that asks caregiver to provide the assessment of their child's asthma control over the past 7 days, on a 4-point scale for the past week. Response choices are: 1 = "Not controlled", 2 = "Somewhat controlled", 3 = "Moderately controlled", 4 = "Well controlled".	Baseline to Week 52
Secondary	Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma severity (CGI-asthma severity)	The Caregiver Global Impression of asthma severity (CGI-Asthma Severity) is a 1-item questionnaire that asks caregivers to provide the assessment of their child's asthma control over the past 7 days, on a 4-point scale for the past week. Response choices are: 1 = "None", 2 = "Mild", 3 = "Moderate", 4 = "Severe".	Baseline to Week 52
Secondary	Part A: Change from baseline to Week 52 in Physician Global Assessment of the child's asthma control (PGA-asthma control).	The Physician Global Assessment of asthma control is a 1-item questionnaire that asks physicians to assess the control of the child's asthma in the past 7 days on a 4 point scale for the past week. Response choices are: 1 = "Not controlled", 2 = "Somewhat controlled", 3 = "Moderately controlled", 4 = "Well controlled".	Baseline to Week 52
Secondary	Part A: Change from baseline to Week 52 in Test for Respiratory and Asthma Control in Kids (TRACK)	TRACK is a validated questionnaire for caregiver completion for preschool aged children with symptoms consistent with asthma. The total score range of 0 to 100. Higher scores indicated better asthma control.	Baseline to Week 52
Secondary	Part A: Change from baseline in blood eosinophil level at Weeks 24 and 52		Baseline to Week 24 and 52
Secondary	Part A: Concentration of dupilumab in serum over time during the 52-week treatment period		Baseline through Week 52
Secondary	Part A: Incidence of treatment-emergent anti-drug antibody (ADA) against dupilumab over time		Baseline through Week 52
Secondary	Part A: IgG response to nonlive vaccination		Baseline through Week 52
Secondary	Part B: Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period	Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period.	Week 52 through Week 104
Secondary	Part B Concentration of dupilumab in serum over time during the 52-week Part B treatment period		Week 52 through Week 104
Secondary	Part B: Incidence of treatment-emergent anti-drug antibodies (ADAs) against dupilumab over time		Week 52 through Week 104