AsthmaPhase 3HORIZONNCT06023589
A Study to Investigate the Efficacy and Safety of Tezepelumab Compared With Placebo in Children 5 to < 12 Years Old With Severe Asthma
A Phase 3 study testing Tezepelumab in people with Asthma, run by AstraZeneca at 147 sites in 22 countries.
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. Read more about this study
- Who is it for?
- Ages 5 to 11 years
- Conditions the study is for
- Asthma
- What is being tested?
- Tezepelumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 231 participants
- Where
- 147 sitesin 22 countries
- Study dates
- 24 Aug 2023to 23 Aug 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
- 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.
- Documented physician diagnosis of severe asthma confirmed and evaluated for at least 6 months prior to Visit 1.
- 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.
- 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.
- Supportive evidence of asthma as documented by one of the following:
Show all 22Show fewer
- Post-BD (albuterol/salbutamol) responsiveness of FEV1 ≥ 10% during Screening (15 to 30 min after administration of 4 puffs of albuterol/salbutamol with a maximum of 12 puffs of reliever medication only if tolerated by the participant) at either Visit 1 or Visit 2.
- If (a) is not achieved at Visit 1 or Visit 2, historical documentation by any of the below prior to Visit 1:
- Post-BD responsiveness of FEV1 ≥ 10%.
- Positive methacholine challenge defined as provocative concentration (PC20) of ≤ 16 mg/mL.
- PEF average daily diurnal variability > 13% over a 2-week period.
- Variability of FEV1 ≥ 12% between any two clinical visits.
- Positive exercise challenge test (defined as a fall in FEV1 of > 12%).
- FeNO ≥ 20 ppb despite confirmed ICS maintenance therapy.
- 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.
- Pre-BD FEV1 >50% and ≤ 95%PN OR FEV1/forced vital capacity (FVC) ratio ≤ 0.85 at either Visit 1 or Visit 2.
- Evidence of uncontrolled asthma, with at least 1 of the below criteria:
- 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.
- 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.
- Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening/Run-in period.
- Asthma symptoms 3 or more days per week in at least 1 week during the Screening/Run-in period.
- Body weight ≥ 16 kg at Visit 1 (Screening) and Visit 3 (Randomisation).
Who cannot join
- History of vocal cord dysfunction, cystic fibrosis, primary ciliary dyskinesia, or chronic rhinosinusitis with nasal polyposis.
- 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.
- 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.
- Change in ICS dose within 1 month prior to Visit 1.
- History of a life-threatening asthma exacerbation resulting in a hypoxic seizure or requiring intubation.
Trial locations and contacts
147 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
147 sites in 22 countries
United States30 sites, 20 recruiting
- Terminated
Research Site
Ann Arbor, Michigan, 48105
- Recruiting
Research Site
Atlanta, Georgia, 30322
- Recruiting
Research Site
Baltimore, Maryland, 21287
- Recruiting
Research Site
Boston, Massachusetts, 02114
- Recruiting
Research Site
Boston, Massachusetts, 02115
- Recruiting
Research Site
Chapel Hill, North Carolina, 27514
- Recruiting
Research Site
Cincinnati, Ohio, 45229-3039
- Recruiting
Research Site
Cleveland, Ohio, 44106
- Withdrawn
Research Site
Columbia, South Carolina, 29203
- Terminated
Research Site
Coppell, Texas, 75019
- Recruiting
Research Site
Dallas, Texas, 75246
- Recruiting
Research Site
Detroit, Michigan, 48201
- Withdrawn
Research Site
Frisco, Texas, 75034
- Recruiting
Research Site
Hawthorne, New York, 10532
- Recruiting
Research Site
Houston, Texas, 77030
- Active, not recruiting
Research Site
La Jolla, California, 92037
- Withdrawn
Research Site
Little Rock, Arkansas, 72202
- Recruiting
Research Site
Long Beach, California, 90806
- Recruiting
Research Site
Montgomery, Alabama, 36106
- Recruiting
Research Site
Northfield, New Jersey, 08225
- Recruiting
Research Site
Oklahoma City, Oklahoma, 73120
- Withdrawn
Research Site
Orange, California, 92868
- Recruiting
Research Site
Phoenix, Arizona, 85016
- Recruiting
Research Site
San Antonio, Texas, 78249
- Recruiting
Research Site
San Diego, California, 92123
- Terminated
Research Site
Savannah, Georgia, 31406
- Withdrawn
Research Site
Schenectady, New York, 12304
- Recruiting
Research Site
Staten Island, New York, 10305
- Withdrawn
Research Site
Temple, Texas, 76508
- Recruiting
Research Site
Toledo, Ohio, 43617
China13 sites, 12 recruiting
- Recruiting
Research Site
Beijing, 100191
- Recruiting
Research Site
Changchun, 130021
- Recruiting
Research Site
Hohhot, 010050
- Recruiting
Research Site
Lanzhou, 730000
- Recruiting
Research Site
Nanjing, 210008
- Recruiting
Research Site
Shanghai, 200062
- Withdrawn
Research Site
Shanghai, 200127
- Recruiting
Research Site
Shenyang, 110004
- Recruiting
Research Site
Shenzhen, 518026
- Not yet recruiting
Research Site
Tianjin, 300201
- Recruiting
Research Site
Wuxi, 214023
- Not yet recruiting
Research Site
Zhanjiang, 524001
- Not yet recruiting
Research Site
Zhongshan, 528400
Argentina10 sites, 8 recruiting
- Recruiting
Research Site
Buenos Aires, 1426
- Recruiting
Research Site
Buenos Aires, C1121ABE
- Recruiting
Research Site
Buenos Aires, C1122
- Terminated
Research Site
CABA, C1028AAP
- Recruiting
Research Site
Florida, B1602DQD
- Recruiting
Research Site
Lanus, B1824KAJ
- Recruiting
Research Site
Lobos, 7240
- Recruiting
Research Site
Mendoza, M5500CCG
- Terminated
Research Site
Quilmes, B1878FNR
- Recruiting
Research Site
Rosario, 2000
Japan10 sites, 9 recruiting
- Recruiting
Research Site
Fukuoka, 811-1394
- Recruiting
Research Site
Fukuoka, 813-0017
- Recruiting
Research Site
Fukuyama, 720-8520
- Recruiting
Research Site
Funabashi-shi, 273-8588
- Recruiting
Research Site
Nara, 630-8581
- Recruiting
Research Site
Odawara, 250-0055
- Recruiting
Research Site
Ōtsu, 520-0804
- Recruiting
Research Site
Saga, 840-8571
- Recruiting
Research Site
Shimotsuga-gun, 321-0293
- Withdrawn
Research Site
Yokohama, 223-0059
France9 sites, 8 recruiting
- Recruiting
Research Site
Brest, 29609
- Suspended
Research Site
Bron, 69500
- Recruiting
Research Site
Créteil, 94010
- Recruiting
Research Site
Marseille, 13005
- Recruiting
Research Site
Paris, 75012
- Recruiting
Research Site
Paris, 75015
- Recruiting
Research Site
Paris, 75019
- Recruiting
Research Site
Rouen, 76031
- Recruiting
Research Site
Vandœuvre-lès-Nancy, 54511
South Africa8 sites, 6 recruiting
- Recruiting
Research Site
Bellville, 7531
- Recruiting
Research Site
Cape Town, 7925
- Active, not recruiting
Research Site
Durban, 3630
- Recruiting
Research Site
Durban, 4001
- Recruiting
Research Site
Middelburg, 1055
- Withdrawn
Research Site
Thabazimbi, 0380
- Recruiting
Research Site
Vereeniging, 1935
- Recruiting
Research Site
Welkom, 9460
Spain8 sites, 7 recruiting
- Recruiting
Research Site
Badalona, 08916
- Recruiting
Research Site
Barcelona, 08035
- Recruiting
Research Site
Esplugues de Llobregat (Barc), 08950
- Recruiting
Research Site
Madrid, 28009
- Recruiting
Research Site
Sabadell, 08208
- Recruiting
Research Site
Valencia, 46010
- Withdrawn
Research Site
Valencia, 46026
- Recruiting
Research Site
Villarreal, 12540
United Kingdom8 sites, 7 recruiting
- Recruiting
Research Site
Birmingham, B4 6NH
- Recruiting
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Bradford, BD9 6RJ
- Recruiting
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Bristol, BS2 8BJ
- Withdrawn
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Glasgow, G3 8SJ
- Recruiting
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Leicester, LE1 5WW
- Recruiting
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London, SE5 9RS
- Recruiting
Research Site
Nottingham, NG7 2UH
- Recruiting
Research Site
Stoke-on-Trent, ST4 6QG
Brazil7 sites, 5 recruiting
- Recruiting
Research Site
Blumenau, 89030-101
- Recruiting
Research Site
Curitiba, 80060-240
- Withdrawn
Research Site
Salvador, 40060-330
- Active, not recruiting
Research Site
São Paulo, 01227-200
- Recruiting
Research Site
São Paulo, 04024-002
- Recruiting
Research Site
São Paulo, 05430-010
- Recruiting
Research Site
Sorocaba, 18040-425
Canada5 sites, 5 recruiting
- Recruiting
Research Site
Burlington, Ontario, L7L 6W6
- Recruiting
Research Site
Edmonton, Alberta, T6G 1C9
- Recruiting
Research Site
Hamilton, Ontario, L8S 1G5
- Recruiting
Research Site
Montreal, Quebec, H4A 3J1
- Recruiting
Research Site
Windsor, Ontario, N8X 2G1
Mexico4 sites, 4 recruiting
- Recruiting
Research Site
Chihuahua City, 31000
- Recruiting
Research Site
Guadalajara, 44100
- Not yet recruiting
Research Site
Mexico City, 06100
- Recruiting
Research Site
Veracruz, 91910
Philippines4 sites, 4 recruiting
- Recruiting
Research Site
Iloilo City, 5000
- Recruiting
Research Site
Las Piñas, 1740
- Recruiting
Research Site
Quezon, 1100
- Recruiting
Research Site
Santa Rosa, 4026
South Korea4 sites, 3 recruiting
- Withdrawn
Research Site
Seongnam-si, 13496
- Recruiting
Research Site
Seongnam-si, 13620
- Recruiting
Research Site
Seoul, 03181
- Recruiting
Research Site
Seoul, 03722
Thailand4 sites, 4 recruiting
- Recruiting
Research Site
Bangkok, 10330
- Recruiting
Research Site
Bangkoknoi, 10700
- Recruiting
Research Site
Chiang Mai, 50200
- Recruiting
Research Site
Muang, 40002
Turkey (Türkiye)4 sites, 4 recruiting
- Recruiting
Research Site
Bursa, 16059
- Recruiting
Research Site
Istanbul, 34899
- Recruiting
Research Site
Izmir, 35210
- Recruiting
Research Site
Yenimahalle, 06500
Ukraine4 sites, 4 recruiting
- Recruiting
Research Site
Chernivtsi, 58002
- Recruiting
Research Site
Ivano-Frankivsk, 76000
- Recruiting
Research Site
Kyiv, 03038
- Recruiting
Research Site
Kyiv, 04050
Colombia3 sites
- Withdrawn
Research Site
Bogotá, 110231
- Withdrawn
Research Site
Bogotá
- Withdrawn
Research Site
Medellín, 050034
Hungary3 sites, 2 recruiting
- Completed
Research Site
Debrecen, 4031
- Recruiting
Research Site
Szeged, 6720
- Recruiting
Research Site
Szigetvár, 7900
Italy3 sites, 3 recruiting
- Recruiting
Research Site
Genova, 16147
- Recruiting
Research Site
Pavia, 27100
- Recruiting
Research Site
Roma, 00165
Netherlands2 sites, 2 recruiting
- Recruiting
Research Site
Amsterdam, 1105 AZ
- Recruiting
Research Site
Rotterdam, 3015 GD
Poland2 sites, 2 recruiting
- Recruiting
Research Site
Lodz, 90-329
- Recruiting
Research Site
Tarnów, 33-100
Romania2 sites, 2 recruiting
- Recruiting
Research Site
Bucharest, 020395
- Recruiting
Research Site
Bucharest, 050159
About this study
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)
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.
Read the detailed description
This is a phase-3 multicentre, double-blind, parallel-group placebo-controlled, randomised study.
The study will comprise of:
- Screening/Run-in period of 4 to 6 weeks,
- 52-week double-blind Treatment period,
- 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 104-week open-label Treatment period prior to the 12-week post-treatment Follow-up period.
- Conditions
- Asthma
- Being tested
- Tezepelumab, Placebo
- Keywords
- Asthma, Uncontrolled Asthma, Severe Uncontrolled Asthma, Human monoclonal antibody (IgG2λ) cytokine
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TezepelumabBiological
Also called MEDI9929 and AMG157
Participants will be receiving subcutaneous injection of tezepelumab
PlaceboOther
Participants will be receiving subcutaneous injection of matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Tezepelumab | Experimental | Participants will be receiving tezepelumab subcutaneous injection Receives: Biological: Tezepelumab |
| Placebo | Placebo comparator | Participants will be receiving placebo through a subcutaneous injection Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized severe 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.
Measured: From Baseline to Week 52
Secondary outcomes (20)
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.
Measured: From Baseline to Week 52
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]).
Measured: From Baseline to Week 52
Time to first severe asthma exacerbation
Time to first severe asthma exacerbation will be assessed.
Measured: From Baseline to Week 52
Proportion of participants with ≥ 1 severe asthma exacerbation
Proportion of participants with ≥ 1 severe asthma exacerbation will be assessed.
Measured: From Baseline to Week 52
AAER associated with ER visit or hospitalisation
AAER will be assessed in association with ER visits or hospitalisations.
Measured: From Baseline to Week 52
Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations
Cumulative exposure to systemic corticosteroids for treatment of severe asthma exacerbations over the 52 week double-blind treatment period
Measured: From Baseline to Week 52
Change from baseline in Paediatric Asthma Quality of Life Questionnaire (PAQLQ-(S)-IA) total score
Change from baseline of PAQLQ-(S)-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-(S)-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-(S)-IA score is the mean of all 23 responses, and the individual domain scores are the means of the items in those domains.
Measured: From Baseline to Week 52
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.
Measured: From Baseline to Week 52
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
Measured: From Baseline to Week 52
Change from baseline in weekly mean rescue medication use
Change from baseline in weekly mean rescue medication use will be assessed.
Measured: From Baseline to Week 52
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.
Measured: From Baseline to Week 52
Change from baseline in blood eosinophil count
Change from baseline in blood eosinophil count will be assessed.
Measured: From Baseline to Week 52
Change from baseline in fractional exhaled nitric oxide (FeNO)
Change from baseline in FeNO will be assessed.
Measured: From Baseline to Week 52
Change from baseline in total serum IgE
Change from baseline in total serum IgE will be assessed.
Measured: From Baseline to Week 52
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.
Measured: From Baseline to Week 52
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.
Measured: From Baseline to Week 52
Number of participant/caregiver health-related absences
Mean number of participant/caregiver health-related absences from work/school due to asthma will be assessed.
Measured: From Baseline to Week 52
Serum concentrations of tezepelumab
To evaluate the pharmacokinetics of tezepelumab.
Measured: At Baseline, Week 4, Week 24, and Week 52
Incidence of anti-drug antibodies (ADAs)
To evaluate the immunogenicity of tezepelumab.
Measured: At Baseline, and from time of first dose at Week 0 to end of study at week 64
Incidence of neutralising antibodies (nAbs)
To evaluate the immunogenicity of tezepelumab.
Measured: At Baseline, and from time of first dose at Week 0 to end of study at week 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2023
- Study start24 Aug 2023
- Primary completion31 May 2028 (estimated)
- Study completion23 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 2:1 ratio to either tezepelumab or matching placebo both administered subcutaneously
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 231 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06023589
- Sponsor's protocol ID
- D5180C00016
- Acronym
- HORIZON
- Status last verified
- Oct 2026
- First submitted
- 20 Jul 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.