Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents

Inclusion Criteria:

1. Participant and/or parent guardian must be able to understand and provide informedconsent and age-appropriate assent

2. Are male and female aged 6-17 years at Visit 0

3. Participant has a primary place of residence in one of the pre-selected recruitmentcensus tracts as outlined in the Protocol CAUSE01 Manual of Operations (MOP).Participants who do not live in the pre-selected census tracts but live within theOffice of Management and Budget (OMB) defined Metropolitan Statistical Area and havepublicly funded health insurance will qualify for inclusion.

4. Participant has a diagnosis of asthma made > 1 year prior to recruitment.Participants who received an asthma diagnosis by a clinician ≤1 year prior torecruitment must report that their respiratory symptoms were present for more than 1year prior to recruitment.

5. Participant has had at least two asthma exacerbations in the prior year (defined asa requirement for systemic corticosteroids and/or hospitalization).

6. At Visit 0 (screening), participant must have the following requirement for asthmacontroller medication:

7. Participants aged 6 to 11 years: treatments with at least fluticasone 250 mcgdry powder inhaler (DPI) one puff twice daily or its equivalent.

8. Participants aged 12 years and older, treatment with at least fluticasone 250mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or itsequivalent.

9. Have peripheral blood eosinophils ≥150 cells/mcl and/or FeNO ≥ 20ppb obtained atVisit 0 or via another CAUSE protocol within 6 months.

10. Are able to perform acceptable and repeatable spirometry per American ThoracicSociety (ATS) criteria prior to randomization.

11. Have documentation of current medical insurance with prescription coverage at Visit

Exclusion Criteria:

1. Parent or guardian is not able or willing to give written informed consent or complywith study protocol.

2. Have concurrent medical problems that would require systemic corticosteroids orother immunomodulators during the study.

3. Are currently receiving immunotherapy.

4. Are currently receiving treatment with a biologic therapy or have received abiologic therapy within 3 months prior to randomization.

5. Are currently requiring greater than fluticasone 500 mcg bid plus long-acting betaagonist (LABA) one puff twice daily or its equivalent plus Long-acting muscarinicantagonists (LAMA) and/or individuals using oral corticosteroids daily or everyother day for more than 14 days at the time of Visit 0.

6. Are currently pregnant or lactating, or plan to become pregnant during the time ofstudy participation. Participants of child-bearing potential (post-menarche) must beabstinent or use a medically acceptable birth control method throughout the study (i.e., oral subcutaneous, mechanical, or surgical contraception). Males who aresexually active must agree to use an acceptable method of birth control (i.e.,barrier methods with vaginal spermicide) or have a partner practicing an approvedbirth control method.

7. Have a known, pre-existing clinically important lung condition other than asthma.

8. Have a current malignancy or previous history of cancer in remission for less than 12 months prior to randomization.

9. Is a current smoker or is currently using any electronic cigarette or vaping device (e.g. e-cigarette, e- cig, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vapepods).

10. Have a known immunodeficiency disease.

11. Have a known, active pre-existing parasitic infection or are undergoing treatmentfor a parasitic infection. Once the participant has been successfully treated, theparticipant may be reevaluated.

12. Use of investigational drugs within 4 weeks of randomization

13. Have past or current medical problems or findings from physical examination orlaboratory testing that are not listed above, which, in the opinion of the siteinvestigator, may pose additional risks from participation in the study, mayinterfere with the participant's ability to comply with study requirements or thatmay impact the quality or interpretation of the data obtained from the study.

14. Will not allow the study clinician, an asthma specialist, to manage their diseasefor the duration of the study or who is not willing to change their asthmamedications to follow the Protocol CAUSE- 01 PANDA.

15. Have a known history of allergic reaction to dupilumab.

16. Have had a life-threatening asthma exacerbation in the last 2 years requiringintubation, mechanical ventilation or resulting in a hypoxic seizure.

17. Have received a live (attenuated) vaccine within 4 weeks of Visit 0.

18. Have an eosinophil count of ≥1500 cells/mcl at Visit 0.

Potential participants may be reassessed as outlined in the Protocol CAUSE-01 MOP.