asthma

Primary Objectives: To assess the effect of dupilumab on lung function and related changes in airway volumes detectable by functional respiratory imaging. Secondary Objectives: To evaluate the effect of dupilumab at Week 24 on bronchodynamics, hyperinflation, airway resistance, airway wall thickness, ventilation defects and mucus plugging derived from high-resolution computed tomography (HRCT) scans, patient-reported outcomes, FeNO and spirometry. To evaluate safety of dupilumab

Dupilumab

Dupilumab

injection

300mg/2mL

Primary Endpoints:
1. Change from baseline to Week 24 in prebronchodilator FEV1
2. Percent change from baseline to Week 24 in
regional airway volumes corrected for lung volume
([s]iVaw) at total lung capacity (TLC)

Efficacy endpoints:
• Percent change from baseline to Week 24 in
regional airway volumes corrected for lung volume
([s]iVaw) at functional residual capacity (FRC)
• Percent change from baseline to Week 24 in
regional airway resistance corrected for lung volume
([s]iRaw) at TLC
• Percent change from baseline to Week 24 in
regional airway resistance corrected for lung volume
([s]iRaw) at FRC
• Change from baseline to Week 24 in lobar volumes
(iVlobes) at TLC
• Change from baseline to Week 24 in HRCT-based
internal airflow distribution (IAD)
• Change from baseline to Week 24 in image-based
ventilation/perfusion (iV/Q) at TLC
• Change from baseline to Week 24 in FeNO
• Achievement of FeNO <25 parts per billion (ppb) at
Week 24
• Change from baseline to Week 24 in postbronchodilator FEV1
• Change from baseline to Week 24 in ACQ-7

Safety:
• Incidence of treatment emergent adverse events
(TEAE) and serious adverse events (SAE) including
clinically significant changes in vital signs and
laboratory abnormalities
• Incidence of adverse events of special interest
(AESI)

I 01. 18 to 70 years of age inclusive with the diagnosis of asthma based on Global Strategy for
Asthma Management and Prevention (GINA) 2019 (1) at the time of signing the informed
consent.
I 02. History of ≥1 exacerbation(s) in the previous year before V1.
Exacerbation is defined as deterioration of asthma that results in emergency treatment,
hospitalization due to asthma, or treatment with systemic steroids.
I 03. Uncontrolled moderate to severe asthma (ACQ-5 ≥1.5) at V1 and V2, prior to
randomization.
I 04. Pre-bronchodilator FEV1 ≤80% of predicted normal at V1 and V2, prior to randomization.
I 05. Exhibit bronchodilator reversibility (≥12% and 200 mL improvement in FEV1 post SABA
administration) during screening, prior to randomization.
I 06. Blood eosinophil ≥300 cells /µL and FeNO ≥25 ppb during screening and prior to
randomization.
NOTES:
- Historical values of blood eosinophil count meeting the eligibility criterion measured
within 6 months prior to SV1 in the absence of OCS treatment are allowed.
- FeNO value to be checked for eligibility at V2 as well.
I 07. Existing treatment with medium to high dose ICS in combination with a second controller
(eg LABA, LTRA) ± a third controller. The dose regimen should be stable ≥1 month prior
V1 and during screening.
I 08. Willing and able to comply with all clinic visits and study related procedures.
I 09. Male and Female
I 10. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1)
which includes compliance with the requirements and restrictions listed in the informed
consent form (ICF) and in this protocol.

E 01. Current smoker (cigarette or e-cigarette) or cessation of smoking within 1 year prior to
randomization.
E 02. Previous smoker with a smoking history >10 pack-years.
E 03. Known hypersensitivity to dupilumab or any of its excipients.
E 04. A subject who experiences an asthma exacerbation (defined as a deterioration of asthma
that results in emergency treatment, hospitalization due to asthma, or treatment with
systemic steroids) during screening.
E 05. Current acute bronchospasm or status asthmaticus.
E 06. Diagnosed pulmonary (other than asthma) or systemic disease associated with elevated
peripheral eosinophil counts.
E 07. Active tuberculosis, latent untreated tuberculosis or a history of incompletely treated
tuberculosis or non-tuberculous mycobacterial infection unless it is well documented by a
specialist that the patient has been adequately treated and the treatment with a biologic
agent can be initiated, in the medical judgment of the Investigator and/or infectious disease
specialist. Tuberculosis testing would only be performed on a country by country basis
according to the routine clinical practice and the local guidelines if required by Regulatory
Authorities or Ethics Committees.
E 08. History or clinical evidence of COPD including Asthma-COPD Overlap Syndrome
(ACOS) or any other significant lung disease (eg, lung fibrosis, sarcoidosis, interstitial
lung disease, pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome).
E 09. History or current evidence of clinically significant disease in any non-respiratory system
(eg, cardiovascular, hepatic, nervous system, gastrointestinal, endocrinological,
rheumatological, dermatological), which, in the judgment of the Investigator, could
interfere with the study or require treatment that might interfere with the study.
E 10. Current evidence of clinically significant oncological disease, which in the opinion of the
investigator may interfere with the objectives of the study or put the subject at undue risk.
E 11. Patients with any of the following results at V1:
- Positive (or indeterminate) hepatitis B surface antigen (HBsAg) or,
- Positive IgM hepatitis B core antibody (HBcAb) or,
- Positive total HBcAb confirmed by positive HBV DNA or,
- Positive hepatitis C virus antibody (HCVAb) confirmed by positive HCV RNA.
E 12. History of human immunodeficiency virus (HIV) infection or positive HIV serology at V1.
E 13. Any biologic therapy (including experimental treatments and dupilumab) or any other
biologic therapy/immunosuppressant within 3 months prior to V1.
E 14. Treatment with live (attenuated) vaccine within 4 weeks before V1.
For participants who have vaccination with live, attenuated vaccines planned during the
course of the study (based on national vaccination schedule/local guidelines), it will be
determined, after consultation with a physician, whether the administration of vaccine can
be postponed until after the end of the study, or preponed to before the start of the study
without compromising the health of the participant:
- Patients for whom administration of live (attenuated) vaccine can be safely postponed
would be eligible to enroll into the study.
- Patients who have their vaccination preponed can enroll in the study only after a gap of
4 weeks following administration of the vaccine.
E 15. Treatment with oral corticosteroids (OCS) within 2 weeks prior to V1.
E 16. Enrolled in other ongoing studies regardless of the investigational product.
E 17. Treatment with an investigational drug within 1 month or within 5 half-lives (if known),
whichever is longer, prior to V1.
E 18. Suspected or high risk of parasitic infection (helminthic infection), unless clinical and (if
necessary) laboratory assessments have ruled out active infection prior to randomization.
E 19. Females who are lactating, breastfeeding, or who are pregnant.
E 20. Individuals accommodated in an institution because of regulatory or legal order; prisoners
or subjects who are legally institutionalized.
E 21. Patients are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of
the ICH GCP Ordinance E6).
E 22. Patients are employees of the clinical study site or other individuals directly involved in
the conduct of the study, or immediate family members of such individuals.
E 23. Sensitivity to any of the study interventions, or components thereof, or drug or other
allergy that, in the opinion of the Investigator, contraindicates participation in the study.
E 24. Any country-related specific regulation that would prevent the subject from entering the
study.