A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to < 12 Years Old With Severe Asthma

Asthma Clinical Trial

— HORIZON  

Official title:

A Multicentre, Randomised, Double-Blind, Parallel-Group Placebo-Controlled, Phase 3, Efficacy and Safety Study of Tezepelumab in 5 to < 12 Year Old Children With Severe Uncontrolled Asthma (HORIZON)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06023589
• Other study ID #: D5180C00016
• Status: Recruiting
• Phase: Phase 3
• Start date: August 24, 2023
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the efficacy and safety of tezepelumab in pediatric participants with severe uncontrolled asthma on medium to high-dose inhaled corticosteroids (ICS) and at least one additional asthma controller medication with or without oral corticosteroids.

Description:

This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study. The study will comprise of: 1. Screening/Run-in period of 4 to 6 weeks, 2. 52-week double-blind Treatment period, 3. Post-treatment Follow-up period of 12 weeks. Participants will be randomised 2:1 to receive either tezepelumab or placebo administered by (SC) Subcutaneous injections for 52 weeks (double-blind Treatment period). There will then be a 12-week off-treatment Follow-up period for participants who do not continue in the optional open-label Active Treatment Extension period. An optional open-label Active Treatment Extension will allow all eligible participants the opportunity to receive active treatment with tezepelumab. The Active Treatment Extension period of the study will start following the 52-week double-blind Treatment period and will consist of a 24-week open-label Treatment period prior to the 12-week post-treatment Follow-up period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 372
• Est. completion date: December 31, 2027
• Est. primary completion date: April 23, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 11 Years

Eligibility

Inclusion Criteria:

1. Written informed consent from (ICF) at least one parent/caregiver (as per local guidelines) and accompanying informed assent from the participant (where the participant is able to provide assent) prior to admission to the study.

2. Participants must be 5 to < 12 years of age, at the time of signing the assent form (as applicable per local guidelines) and their caregivers signing the ICF and at Visit 3.

3. Documented physician diagnosis of severe asthma for at least 6 months prior to Visit 1.

4. Documented physician-prescribed treatment with a total daily dose of either medium or high dose, for at least 3 months with stable dose = 1 month prior to Visit 1.

5. Documented treatment with at least one additional maintenance asthma controller medication is required according to local guidelines and standard of care; (long-acting beta agonist, leukotriene receptor antagonist, long-acting muscarinic antagonist) for at least 3 months with stable dose = 1 month prior to Visit 1.

6. Evidence of asthma as documented by one of the following:

1. Documented historical BD responsiveness of FEV1 = 10% in the previous 12 months prior to Visit 1 OR

2. Documented historical methacholine challenge result of = 16 mg/mL in the previous 12 months prior to Visit 1 OR

3. Post-BD (albuterol/salbutamol) responsiveness of FEV1 = 10% during Screening (15 to 30 min after administration of 4 puffs of albuterol/salbutamol) at either Visit 1 or Visit 2.

7. History of at least 2 severe asthma exacerbation events OR 1 severe asthma exacerbation event resulting in hospitalisation within 12 months prior to Visit 1.

8. Pre-BD FEV-1 >50% and = 95%PN OR FEV1/forced vital capacity (FVC) ratio = 0.8 at either Visit 1 or Visit 2.

9. Evidence of uncontrolled asthma, with at least 1 of the below criteria:

1. ACQ-IA score = 1.5 at least once during Screening/Run-in, including Visit 3 (prior to Randomisation) for participants = 6 years old at Screening

2. Use of reliever medication, other than as a preventive for exercise induced bronchospasm, on 3 or more days per week for at least 1 week during the Screening/Run-in period

3. Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period

4. Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period

10. Body weight = 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation).

Exclusion Criteria:

1. History of cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with nasal polyposis.

2. History of any clinically significant disease or disorder other than asthma which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.

3. History of a clinically significant deterioration in asthma or asthma exacerbation including those requiring use of systemic corticosteroids or increase in the maintenance dose of oral corticosteroids within 30 days prior to Visit 1.

4. Change in ICS dose within 1 month prior to Visit 1.

5. History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation or mechanical ventilation.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Tezepelumab
Participants will be receiving subcutaneous injection of tezepelumab

Other:
• Placebo
Participants will be receiving subcutaneous injection of matching placebo

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Capital Federal
Argentina	Research Site	Florida
Argentina	Research Site	Lanus Este
Argentina	Research Site	Lobos
Argentina	Research Site	Mendoza
Argentina	Research Site	Quilmes
Argentina	Research Site	Rosario
Brazil	Research Site	Blumenau
Brazil	Research Site	Curitiba
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Brazil	Research Site	Sorocaba
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Windsor	Ontario
China	Research Site	Beijing
China	Research Site	Changchun
China	Research Site	Lanzhou
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Wuxi
Colombia	Research Site	Bogota
Colombia	Research Site	Bogotá
Colombia	Research Site	Medellín
France	Research Site	Brest
France	Research Site	Bron
France	Research Site	Creteil
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Vandoeuvre les Nancy Cedex
Hungary	Research Site	Debrecen
Hungary	Research Site	Szeged
Hungary	Research Site	Szigetvár
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Funabashi-shi
Japan	Research Site	Odawara
Japan	Research Site	Saga-shi
Japan	Research Site	Shimotsuga-gun
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	SeongNam
Korea, Republic of	Research Site	Seongnam-Si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Mexico	Research Site	Chihuahua
Mexico	Research Site	Guadalajara
Mexico	Research Site	Veracruz
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Rotterdam
Philippines	Research Site	Iloilo
Philippines	Research Site	Las Piñas
Philippines	Research Site	Quezon City
Philippines	Research Site	Santa Rosa
Poland	Research Site	Lódz
Poland	Research Site	Tarnow
Poland	Research Site	Tarnów
South Africa	Research Site	Bellville
South Africa	Research Site	Durban
South Africa	Research Site	Durban
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Esplugues De Llobregat (Barc)
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Spain	Research Site	Villarreal (Castellón)
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	London
United Kingdom	Research Site	Nottingham
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Atlanta	Georgia
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cleveland	Ohio
United States	Research Site	Coppell	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Detroit	Michigan
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Montgomery	Alabama
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orange	California
United States	Research Site	Phoenix	Arizona
United States	Research Site	San Diego	California
United States	Research Site	Savannah	Georgia
United States	Research Site	Schenectady	New York
United States	Research Site	Staten Island	New York
United States	Research Site	Temple	Texas
United States	Research Site	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Colombia,  France,  Hungary,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Philippines,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized asthma exacerbation rate (AAER)	To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to < 12 years old with severe uncontrolled asthma compared with placebo.	From Baseline to Week 52
Secondary	Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN)	To assess the effect of tezepelumab on pulmonary function (FEV1) in children with severe uncontrolled asthma compared with placebo. Pre-bronchodilator FEV1% PN will be determined by spirometry at the clinic visit.	From Baseline to Week 52
Secondary	AAER associated with allergic asthma	AAER will be assessed in association with both allergic asthma (defined by a positive perennial allergen using serum specific IgE [FEIA]).	From Baseline to Week 52
Secondary	Time to first severe asthma exacerbation	Time to first severe asthma exacerbation will be assessed.	From Baseline to Week 52
Secondary	Proportion of participants with = 1 severe asthma exacerbation	Proportion of participants with = 1 severe asthma exacerbation will be assessed.	From Baseline to Week 52
Secondary	AAER associated with ER visit or hospitalisation	AAER will be assessed in association with ER visits or hospitalisations.	From Baseline to Week 52
Secondary	Cumulative asthma exacerbation days	The cumulative asthma exacerbation days from baseline to week 52 will be assessed	From Baseline to Week 52
Secondary	Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-IA) total score	Change from baseline of PAQLQ-IA total score will be assessed. The PAQLQ was developed to measure the functional problems (physical, emotional, and social) that are most troublesome to children with asthma. The PAQLQ-IA has 23 questions in 3 domains (symptoms, activity limitation, and emotional function). Participants are asked to think about how they have been during the previous week and respond to each question on a 7-point scale (1 = extremely bothered to 7 = not bothered at all or 1 = all of the time to 7 = none of the time). There are 2 coloured cards (green and blue), which list sets of response options appropriate to different questions. The appropriate card should be used by the participant during completion of each question and then taken back when it is no longer required. The overall PAQLQ-IA score is the mean of all 23 responses and the individual domain scores are the means of the items in those domains.	From Baseline to Week 52
Secondary	Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score	Change from baseline in PASO score will be assessed. The PASO questionnaire will be completed by the caregiver each day from the evening of Treatment period. Caregivers in this study will complete 4 items from the morning assessment capturing night-time asthma symptoms, rescue medication use, night-time awakenings, and maintenance asthma medication use. The evening assessment will capture daytime asthma symptoms, rescue medication use, activity limitation and change in asthma.	From Baseline to Week 52
Secondary	Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score	Change from baseline in ACQ-IA score will be assessed. The ACQ-IA will only be completed for participants = 6 years old at Screening. The ACQ-IA is administered by trained individuals according to standardised instructions to help the child understand concepts like symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of SABA during the past week using a 7-point scale. The ACQ-IA score is calculated by taking the mean of the 6 equally weighted items and ranges from 0 (well controlled) to 6 (extremely poorly controlled). The estimated minimal clinically important difference is 0.5	From Baseline to Week 52
Secondary	Change from baseline in weekly mean rescue medication use	Change from baseline in weekly mean rescue medication use will be assessed.	From Baseline to Week 52
Secondary	Change from baseline in weekly mean number of night-time awakenings	Change from baseline in weekly mean number of night-time awakenings will be assessed.	From Baseline to Week 52
Secondary	Change from baseline in blood eosinophil count	Change from baseline in blood eosinophil count will be assessed.	From Baseline to Week 52
Secondary	Change from baseline in fractional exhaled nitric oxide (FeNO)	Change from baseline in FeNO will be assessed.	From Baseline to Week 52
Secondary	Change from baseline in total serum IgE	Change from baseline in total serum IgE will be assessed.	From Baseline to Week 52
Secondary	Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF)	The effect of tezepelumab on pulmonary function compared with placebo will be assessed using spirometry.	From Baseline to Week 52
Secondary	Number of asthma--related healthcare resource utilization (HRU)	Mean number and type of Asthma specific HRU (eg, unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) will be assessed.	From Baseline to Week 52
Secondary	Number of participant/caregiver health-related absences	Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.	From Baseline to Week 52
Secondary	Serum concentrations of tezepelumab	To evaluate the pharmacokinetics of tezepelumab.	At Baseline, Week 4, Week 24, and Week 52
Secondary	Incidence of anti-drug antibodies (ADAs)	To evaluate the immunogenicity of tezepelumab.	At Baseline, and from time of first dose at Week 0 to end of study at week 64
Secondary	Incidence of neutralising antibodies (nAbs)	To evaluate the immunogenicity of tezepelumab.	At Baseline, and from time of first dose at Week 0 to end of study at week 64