Informations générales (source: ClinicalTrials.gov)
A Multicentre, Randomised, Open-Label, Parallel-Group, Phase IIIb Study to Assess the Potential for Tezepelumab-treated Patients With Severe Asthma to Reduce Background Therapy While Sustaining Asthma Control and Clinical Remission
Interventional
Phase 3
AstraZeneca (Voir sur ClinicalTrials)
septembre 2024
juin 2027
14 août 2025
The objective of this study is to assess the potential for tezepelumab-treated patients
(subcutaneous administration) to reduce maintenance therapy without loss of asthma
control in adolescent and adults with severe asthma..
Study details include:
1. The study duration will be up to 72 weeks.
2. The treatment duration will be up to 68 weeks.
3. The visit frequency will be once every 4 weeks (Q4W).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHI DE CRETEIL | AMEL BOUDJEMAA | 28/08/2025 14:30:05 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Research Site - 13915 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Research Site - 33076 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| Research Site - 34295 - Montpellier - France | Contact (sur clinicalTrials) | ||||
| Research Site - 38700 - La Tronche - France | Contact (sur clinicalTrials) | ||||
| Research Site - 67091 - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Research Site - 69004 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Research Site - 94000 - Créteil - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria at Visit 1 (Screening):
Informed Consent
1. Provision of signed and dated written ICF prior to any mandatory study-specific
procedures, sampling, and analyses for patients who are at or over the age of
majority (as per local law). For patients who are less than the age of majority, in
addition to providing their informed consent, the patients' legally authorised
representative must also provide their informed assent (Appendix A 3).
Age
2. Patients must be 12 to 80 years of age inclusive, at the time of signing the ICF.
Type of Patient and Disease Characteristics
3. Documented medical record history for at least 12 months prior to Visit 1.
4. Documented physician-diagnosed severe asthma within 10 years prior to Visit 1 (ie,
severe asthma was not diagnosed more than 10 years prior) consisting of any of the
following:
1. FEV1 > 12% reversibility, OR
2. Evidence of airflow variability (to show that lung function is altered over
time): FEV1 ≥ 400 mL variability over time, OR
3. Challenge tests that are positive on one of the below:
(i) Methacholine - PD20 ≤ 8 mg/mL (ii) Mannitol - PD15 15% drop on FEV1 out of dose
< than 635 mg of inhaled mannitol (iii) Exercise - 10% fall of FEV1
5. ACQ-5 ≥ 1.5 and < 3.
6. History of physician-diagnosed asthma that requires continuous treatment with
high-dose ICS (as defined by GINA or highest approved dose per posology per country)
plus a LABA for at least 6 months prior to Visit 1 (Appendix I). The ICS and LABA
can be contained within a combination product or given by separate inhalers.
Note: Additional maintenance asthma controller medications (eg, LTRAs, tiotropium,
cromone, theophylline) are allowed.
7. Pre-brochodilator FEV1 > 60% predicted and evidence of FEV1 reversibility of > 12%
within 6 months prior to screening or at screening. Patients with normal lung
function (FEV1 > 80%) need evidence of airflow variability as per inclusion
criterion 4.
8. Documented history of at least one asthma exacerbation requiring OCS bursts or
requiring hospitalization within 12 months prior to Visit 1. An asthma exacerbation
will be defined as a worsening of asthma symptoms that leads to any of the
following:
1. A temporary bolus/burst of systemic corticosteroids for at least 3 consecutive
days to treat symptoms of asthma worsening; a single depo-injectable dose of
corticosteroids will be considered equivalent to a 3-day bolus/burst of
systemic corticosteroids
2. Or, an ER visit (defined as evaluation and treatment for < 24 hours in ER) due
to asthma that required systemic corticosteroids (as per above)
3. Or, an in-patient hospitalisation (defined as admission to an inpatient
facility and/or evaluation and treatment in a healthcare facility for ≥ 24
hours).
Sex and Contraceptive/Barrier Requirements
9. Male or female.
Female patients:
- Contraceptive use by women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies. Women of nonchildbearing potential are defined as women who are either
permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy) or who are postmenopausal. Women will be considered
postmenopausal if they have been amenorrhoeic for 12 months prior to the
planned start date of the induction phase without an alternative medical cause.
- The following age-specific requirements apply:
- Women < 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous
hormonal treatment and follicle-stimulating hormone levels in the
postmenopausal range.
- Women ≥ 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatment.
- Adolescents: if patient is female and has reached menarche or has reached
Tanner stage 3 breast development (even if not having reached menarche),
the patient will be considered a WOCBP.
10. WOCBP must be willing to use one of the methods of contraception described
hereafter, from the time of signing the ICF throughout the study and 16 weeks after
last tezepelumab administration:
- Combined (oestrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation: oral, intravaginal, transdermal
- Progestogen-only hormonal contraception associated with inhibition of
ovulation: oral, injectable, implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomised partner (vasectomised partner is a highly effective birth control
method provided that the partner is the sole sexual partner of the WOCBP
patient and that the vasectomised partner has received medical assessment of
the surgical success)
- Sexual abstinence: it is considered a highly effective method only if defined
as refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments. The reliability of sexual abstinence
needs to be evaluated in relation to the duration of the study and the
preferred and usual lifestyle of the patient.
- Cessation of contraception after this point should be discussed with a
responsible physician
Inclusion Criteria 5.1.2 Treatment Induction Phase at Visit 2 (Week 0):
Before dosing with tezepelumab at Week 0, patients should fulfil the following
criteria:
11. ACQ-5 ≥ 1.5 and < 3.
12. Demonstrated proper inhaler technique (patients with improper technique at screening
may be trained during screening, but must demonstrate proper technique before
enrollment).
13. No excessive SABA use (should be < 5 puffs/day) or for patients using SMART therapy
outside the US, no excessive use of SYMBICORT (should be ≤ 8 inhalations/day) or for
US patients, no excessive use of AIRSUPRA (should be ≤ 12 inhalations/day).
Exclusion Criteria:
Medical Conditions
1. Any clinically important pulmonary disease other than asthma (eg, active lung
infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary
fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung
cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or
pulmonary or systemic diseases, other than asthma, that are associated with elevated
peripheral EOS counts (eg, allergic bronchopulmonary aspergillosis/mycosis,
Churg-Strauss syndrome, hypereosinophilic syndrome).
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal,
hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, psychiatric, or major physical impairment that is not stable in the
opinion of the investigator and could:
- Affect the safety of the patient throughout the study
- Influence the findings of the study or the interpretation
- Impede the patient's ability to complete the entire duration of study.
3. A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has
not been treated with, or has failed to respond to, standard of care therapy.
4. Current smokers or patients with smoking history ≥ 10 pack-years and patients using
vaping products, including electronic cigarettes. Former smokers with a smoking
history of < 10 pack-years and users of vaping or e-cigarette products must have
stopped for at least 6 months prior to Visit 1 to be eligible.
5. History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
6. Tuberculosis requiring treatment within the 12 months prior to Visit 1.
7. History of known immunodeficiency disorder including a positive human
immunodeficiency virus test at Visit 1, or the patient taking antiretroviral
medications as determined by medical history and/or patient's verbal report.
8. Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures
requiring general anaesthesia or inpatient status for > 1 day during the conduct of
the study.
9. Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically
significant COVID-19 sequelae.
Prior/Concomitant Therapy
10. Receipt of any marketed or investigational biologic agent within 4 months or 5
half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational
nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to
Visit 1.
11. OCS-dependent patients (received chronic OCS therapy [prednisone ≥ 5 mg/day or
equivalent]) for at least 3 months preceding Visit 1.
12. Daily use of maintenance corticosteroids for any reason.
13. Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate,
cyclosporine, etc.), except for OCS used in the treatment of asthma/asthma
exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior
to Visit 1.
14. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
15. Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during
the study.
16. Patients that have been treated with bronchial thermoplasty in the last 12 months
prior to Visit 1.
Prior/Concurrent Clinical Study Experience
17. Known history of sensitivity to any component of the tezepelumab formulation or a
history of drug or other allergy that, in the opinion of the investigator or medical
monitor, contraindicates their participation.
18. History of anaphylaxis or documented immune complex disease (Type III
hypersensitivity reactions) following any biologic therapy.
19. Concurrent enrolment in another clinical study involving an IMP.
Diagnostic Assessments
20. Any clinically meaningful abnormal finding in physical examination, haematology,
clinical chemistry at Visit 1 which, in the opinion of the investigator, may put the
patient at risk because of his/her participation in the study, or may influence the
results of the study, or the patient's ability to complete the entire duration of
the study.
21. Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 times
the ULN at Visit 1.
22. Positive hepatitis B surface antigen, hepatitis C virus antibody serology at
screening, or a positive medical history for hepatitis B or C. Patients with a
history of hepatitis B vaccination without a history of hepatitis B are allowed to
participate.
Other Exclusions
23. Involvement in the planning and/or conduct of the study (applies to AstraZeneca
staff and/or site staff), or patients employed by or relatives of the employees of
the site or AstraZeneca.
24. Judgement by the investigator that the patient should not participate in the study
if the patient is unlikely to comply with study procedures, restrictions, and
requirements.
25. For women only: Pregnant, breastfeeding, or lactating women. A serum β-HCG pregnancy
test must be drawn for WOCBP at the screening visit. If the results of the serum
β-HCG cannot be obtained prior to dosing of the IMP, a patient may be enrolled on
the basis of a negative urine pregnancy test, though serum β-HCG must still be
obtained. If either test is positive, the patient should be excluded. Since urine
and serum tests may miss a pregnancy in the first days after conception, relevant
menstrual history and sexual history, including methods of contraception, should be
considered. Any patient whose menstrual and/or sexual history suggests the
possibility of early pregnancy should be excluded.
Informed Consent
1. Provision of signed and dated written ICF prior to any mandatory study-specific
procedures, sampling, and analyses for patients who are at or over the age of
majority (as per local law). For patients who are less than the age of majority, in
addition to providing their informed consent, the patients' legally authorised
representative must also provide their informed assent (Appendix A 3).
Age
2. Patients must be 12 to 80 years of age inclusive, at the time of signing the ICF.
Type of Patient and Disease Characteristics
3. Documented medical record history for at least 12 months prior to Visit 1.
4. Documented physician-diagnosed severe asthma within 10 years prior to Visit 1 (ie,
severe asthma was not diagnosed more than 10 years prior) consisting of any of the
following:
1. FEV1 > 12% reversibility, OR
2. Evidence of airflow variability (to show that lung function is altered over
time): FEV1 ≥ 400 mL variability over time, OR
3. Challenge tests that are positive on one of the below:
(i) Methacholine - PD20 ≤ 8 mg/mL (ii) Mannitol - PD15 15% drop on FEV1 out of dose
< than 635 mg of inhaled mannitol (iii) Exercise - 10% fall of FEV1
5. ACQ-5 ≥ 1.5 and < 3.
6. History of physician-diagnosed asthma that requires continuous treatment with
high-dose ICS (as defined by GINA or highest approved dose per posology per country)
plus a LABA for at least 6 months prior to Visit 1 (Appendix I). The ICS and LABA
can be contained within a combination product or given by separate inhalers.
Note: Additional maintenance asthma controller medications (eg, LTRAs, tiotropium,
cromone, theophylline) are allowed.
7. Pre-brochodilator FEV1 > 60% predicted and evidence of FEV1 reversibility of > 12%
within 6 months prior to screening or at screening. Patients with normal lung
function (FEV1 > 80%) need evidence of airflow variability as per inclusion
criterion 4.
8. Documented history of at least one asthma exacerbation requiring OCS bursts or
requiring hospitalization within 12 months prior to Visit 1. An asthma exacerbation
will be defined as a worsening of asthma symptoms that leads to any of the
following:
1. A temporary bolus/burst of systemic corticosteroids for at least 3 consecutive
days to treat symptoms of asthma worsening; a single depo-injectable dose of
corticosteroids will be considered equivalent to a 3-day bolus/burst of
systemic corticosteroids
2. Or, an ER visit (defined as evaluation and treatment for < 24 hours in ER) due
to asthma that required systemic corticosteroids (as per above)
3. Or, an in-patient hospitalisation (defined as admission to an inpatient
facility and/or evaluation and treatment in a healthcare facility for ≥ 24
hours).
Sex and Contraceptive/Barrier Requirements
9. Male or female.
Female patients:
- Contraceptive use by women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies. Women of nonchildbearing potential are defined as women who are either
permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy) or who are postmenopausal. Women will be considered
postmenopausal if they have been amenorrhoeic for 12 months prior to the
planned start date of the induction phase without an alternative medical cause.
- The following age-specific requirements apply:
- Women < 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of exogenous
hormonal treatment and follicle-stimulating hormone levels in the
postmenopausal range.
- Women ≥ 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous
hormonal treatment.
- Adolescents: if patient is female and has reached menarche or has reached
Tanner stage 3 breast development (even if not having reached menarche),
the patient will be considered a WOCBP.
10. WOCBP must be willing to use one of the methods of contraception described
hereafter, from the time of signing the ICF throughout the study and 16 weeks after
last tezepelumab administration:
- Combined (oestrogen and progestogen containing) hormonal contraception
associated with inhibition of ovulation: oral, intravaginal, transdermal
- Progestogen-only hormonal contraception associated with inhibition of
ovulation: oral, injectable, implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomised partner (vasectomised partner is a highly effective birth control
method provided that the partner is the sole sexual partner of the WOCBP
patient and that the vasectomised partner has received medical assessment of
the surgical success)
- Sexual abstinence: it is considered a highly effective method only if defined
as refraining from heterosexual intercourse during the entire period of risk
associated with the study treatments. The reliability of sexual abstinence
needs to be evaluated in relation to the duration of the study and the
preferred and usual lifestyle of the patient.
- Cessation of contraception after this point should be discussed with a
responsible physician
Inclusion Criteria 5.1.2 Treatment Induction Phase at Visit 2 (Week 0):
Before dosing with tezepelumab at Week 0, patients should fulfil the following
criteria:
11. ACQ-5 ≥ 1.5 and < 3.
12. Demonstrated proper inhaler technique (patients with improper technique at screening
may be trained during screening, but must demonstrate proper technique before
enrollment).
13. No excessive SABA use (should be < 5 puffs/day) or for patients using SMART therapy
outside the US, no excessive use of SYMBICORT (should be ≤ 8 inhalations/day) or for
US patients, no excessive use of AIRSUPRA (should be ≤ 12 inhalations/day).
Exclusion Criteria:
Medical Conditions
1. Any clinically important pulmonary disease other than asthma (eg, active lung
infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary
fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung
cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or
pulmonary or systemic diseases, other than asthma, that are associated with elevated
peripheral EOS counts (eg, allergic bronchopulmonary aspergillosis/mycosis,
Churg-Strauss syndrome, hypereosinophilic syndrome).
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal,
hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, psychiatric, or major physical impairment that is not stable in the
opinion of the investigator and could:
- Affect the safety of the patient throughout the study
- Influence the findings of the study or the interpretation
- Impede the patient's ability to complete the entire duration of study.
3. A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has
not been treated with, or has failed to respond to, standard of care therapy.
4. Current smokers or patients with smoking history ≥ 10 pack-years and patients using
vaping products, including electronic cigarettes. Former smokers with a smoking
history of < 10 pack-years and users of vaping or e-cigarette products must have
stopped for at least 6 months prior to Visit 1 to be eligible.
5. History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
6. Tuberculosis requiring treatment within the 12 months prior to Visit 1.
7. History of known immunodeficiency disorder including a positive human
immunodeficiency virus test at Visit 1, or the patient taking antiretroviral
medications as determined by medical history and/or patient's verbal report.
8. Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures
requiring general anaesthesia or inpatient status for > 1 day during the conduct of
the study.
9. Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically
significant COVID-19 sequelae.
Prior/Concomitant Therapy
10. Receipt of any marketed or investigational biologic agent within 4 months or 5
half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational
nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to
Visit 1.
11. OCS-dependent patients (received chronic OCS therapy [prednisone ≥ 5 mg/day or
equivalent]) for at least 3 months preceding Visit 1.
12. Daily use of maintenance corticosteroids for any reason.
13. Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate,
cyclosporine, etc.), except for OCS used in the treatment of asthma/asthma
exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior
to Visit 1.
14. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
15. Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during
the study.
16. Patients that have been treated with bronchial thermoplasty in the last 12 months
prior to Visit 1.
Prior/Concurrent Clinical Study Experience
17. Known history of sensitivity to any component of the tezepelumab formulation or a
history of drug or other allergy that, in the opinion of the investigator or medical
monitor, contraindicates their participation.
18. History of anaphylaxis or documented immune complex disease (Type III
hypersensitivity reactions) following any biologic therapy.
19. Concurrent enrolment in another clinical study involving an IMP.
Diagnostic Assessments
20. Any clinically meaningful abnormal finding in physical examination, haematology,
clinical chemistry at Visit 1 which, in the opinion of the investigator, may put the
patient at risk because of his/her participation in the study, or may influence the
results of the study, or the patient's ability to complete the entire duration of
the study.
21. Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 times
the ULN at Visit 1.
22. Positive hepatitis B surface antigen, hepatitis C virus antibody serology at
screening, or a positive medical history for hepatitis B or C. Patients with a
history of hepatitis B vaccination without a history of hepatitis B are allowed to
participate.
Other Exclusions
23. Involvement in the planning and/or conduct of the study (applies to AstraZeneca
staff and/or site staff), or patients employed by or relatives of the employees of
the site or AstraZeneca.
24. Judgement by the investigator that the patient should not participate in the study
if the patient is unlikely to comply with study procedures, restrictions, and
requirements.
25. For women only: Pregnant, breastfeeding, or lactating women. A serum β-HCG pregnancy
test must be drawn for WOCBP at the screening visit. If the results of the serum
β-HCG cannot be obtained prior to dosing of the IMP, a patient may be enrolled on
the basis of a negative urine pregnancy test, though serum β-HCG must still be
obtained. If either test is positive, the patient should be excluded. Since urine
and serum tests may miss a pregnancy in the first days after conception, relevant
menstrual history and sexual history, including methods of contraception, should be
considered. Any patient whose menstrual and/or sexual history suggests the
possibility of early pregnancy should be excluded.