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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT06023589
• Collaborator: Amgen (Industry)
• Enrollment: 372
• Locations: 39
• Arms: 2
• Anticipated Duration (Months): 52.6
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Tezepelumab; Other: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 372 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneouslyParticipants will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-Blind
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Aug 24, 2023
• Anticipated Primary Completion Date: May 3, 2027
• Anticipated Study Completion Date: Jan 10, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tezepelumab Participants will be receiving tezepelumab subcutaneous injection	Biological: Tezepelumab; Participants will be receiving subcutaneous injection of tezepelumab; Other Names: MEDI9929 and AMG157
Placebo Comparator: Placebo Participants will be receiving placebo through a subcutaneous injection	Other: Placebo; Participants will be receiving subcutaneous injection of matching placebo

Outcome Measures

Primary Outcome Measures

1. Annualized asthma exacerbation rate (AAER) [From Baseline to Week 52]

   To assess the effect of tezepelumab on severe asthma exacerbations in children 5 to < 12 years old with severe uncontrolled asthma compared with placebo.

Secondary Outcome Measures

1. Change from baseline in pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1) percent predicted normal (PN) [From Baseline to Week 52]

   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.

2. AAER associated with allergic asthma [From Baseline to Week 52]

   AAER will be assessed in association with both allergic asthma (defined by a positive perennial allergen using serum specific IgE [FEIA]).

3. Time to first severe asthma exacerbation [From Baseline to Week 52]

   Time to first severe asthma exacerbation will be assessed.

4. Proportion of participants with ≥ 1 severe asthma exacerbation [From Baseline to Week 52]

   Proportion of participants with ≥ 1 severe asthma exacerbation will be assessed.

5. AAER associated with ER visit or hospitalisation [From Baseline to Week 52]

   AAER will be assessed in association with ER visits or hospitalisations.

6. Cumulative asthma exacerbation days [From Baseline to Week 52]

   The cumulative asthma exacerbation days from baseline to week 52 will be assessed

7. Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-IA) total score [From Baseline to Week 52]

   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.

8. Change from baseline in weekly mean daily Paediatric Asthma Symptom Observer (PASO) score [From Baseline to Week 52]

   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.

9. Change from baseline in Asthma Control Questionnaire - Interviewer Administered (ACQ-IA) score [From Baseline to Week 52]

   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

10. Change from baseline in weekly mean rescue medication use [From Baseline to Week 52]

    Change from baseline in weekly mean rescue medication use will be assessed.

11. Change from baseline in weekly mean number of night-time awakenings [From Baseline to Week 52]

    Change from baseline in weekly mean number of night-time awakenings will be assessed.

12. Change from baseline in blood eosinophil count [From Baseline to Week 52]

    Change from baseline in blood eosinophil count will be assessed.

13. Change from baseline in fractional exhaled nitric oxide (FeNO) [From Baseline to Week 52]

    Change from baseline in FeNO will be assessed.

14. Change from baseline in total serum IgE [From Baseline to Week 52]

    Change from baseline in total serum IgE will be assessed.

15. Change from baseline in pre-bronchodilator (pre-BD) peak expiratory flow (PEF) [From Baseline to Week 52]

    The effect of tezepelumab on pulmonary function compared with placebo will be assessed using spirometry.

16. Number of asthma--related healthcare resource utilization (HRU) [From Baseline to Week 52]

    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.

17. Number of participant/caregiver health-related absences [From Baseline to Week 52]

    Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.

18. Serum concentrations of tezepelumab [At Baseline, Week 4, Week 24, and Week 52]

    To evaluate the pharmacokinetics of tezepelumab.

19. Incidence of anti-drug antibodies (ADAs) [At Baseline, and from time of first dose at Week 0 to end of study at week 64]

    To evaluate the immunogenicity of tezepelumab.

20. Incidence of neutralising antibodies (nAbs) [At Baseline, and from time of first dose at Week 0 to end of study at week 64]

    To evaluate the immunogenicity of tezepelumab.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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

6. 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.

7. 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.

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

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

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

11. 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.

12. 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.

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

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

15. 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

16. 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

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

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

19. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Montgomery	Alabama	United States	36106
2	Research Site	Little Rock	Arkansas	United States	72202
3	Research Site	Savannah	Georgia	United States	31406
4	Research Site	Schenectady	New York	United States	12304
5	Research Site	Oklahoma City	Oklahoma	United States	73120
6	Research Site	Buenos Aires		Argentina	C1121ABE
7	Research Site	Capital Federal		Argentina	C1122AAK
8	Research Site	Lobos		Argentina	7240
9	Research Site	Mendoza		Argentina	M5500GIP
10	Research Site	Rosario		Argentina	2000
11	Research Site	Burlington	Ontario	Canada	L7L 6W6
12	Research Site	Hamilton	Ontario	Canada	L8S 1G5
13	Research Site	Windsor	Ontario	Canada	N8X 2G1
14	Research Site	Montreal	Quebec	Canada	H4A 3J1
15	Research Site	Lanzhou		China	730000
16	Research Site	Shenyang		China	110001
17	Research Site	Bogota		Colombia
18	Research Site	Bogotá		Colombia	110231
19	Research Site	Bron		France	69677
20	Research Site	Creteil		France	94010
21	Research Site	Paris		France	75012
22	Research Site	Paris		France	77019
23	Research Site	Vandoeuvre les Nancy Cedex		France	54511
24	Research Site	Szeged		Hungary	7620
25	Research Site	Szigetvár		Hungary	7900
26	Research Site	Funabashi-shi		Japan	273-8588
27	Research Site	Saga-shi		Japan	840-8571
28	Research Site	Shimotsuga-gun		Japan	321-0293
29	Research Site	Yokohama-shi		Japan	223-0059
30	Research Site	Guadalajara		Mexico	44100
31	Research Site	Amsterdam		Netherlands	1105 AZ
32	Research Site	Rotterdam		Netherlands	3015 GD
33	Research Site	Las Piñas		Philippines	1740
34	Research Site	Santa Rosa		Philippines	4026
35	Research Site	Tarnow		Poland	33-100
36	Research Site	Tarnów		Poland	33-100
37	Research Site	Łódź		Poland	90-302
38	Research Site	Esplugues De Llobregat (Barc)		Spain	08950
39	Research Site	Villarreal (Castellón)		Spain	12540

Sponsors and Collaborators

• AstraZeneca
• Amgen

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT06023589
• Other Study ID Numbers: D5180C00016
• First Posted: Sep 5, 2023
• Last Update Posted: Sep 5, 2023
• Last Verified: Aug 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Asthma; Uncontrolled Asthma; Severe Uncontrolled Asthma; Human monoclonal antibody (IgG2λ) cytokine
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Sep 5, 2023