Ensayos clínicos

Inclusion Criteria: 

Age

• Participant must be 2 to < 6 years of age inclusive, at the time of signing the informed consent form by participants’ parent(s)/caregiver(s)/legal guardian(s).

Type of participant and disease characteristics

• Diagnosis of asthma or recurrent severe asthmatic wheeze that is not controlled with chronic ICS for at least 3 months with stable use of at least low dose ICS for ≥ 1 month prior to Screening Visit 1 with evidence of uncontrolled asthma and/or recurrent severe asthmatic wheeze*. * Uncontrolled asthma and/or recurrent severe asthmatic wheeze is defined as participants with at least 2 episodes of asthma exacerbations (defined as acute worsening of respiratory symptoms/wheeze that required treatment for at least 5 days with an increase in ICS dose or 3 days of SCS in the previous year or 1 episode of hospitalization in the past year for asthma) during which the participant required treatment with ICS or SCS.
• At least one additional major criterion from the modified asthma predictive index:
  • Physician diagnosed Atopic Dermatitis.
  • Allergic sensitization to at least 1 aeroallergen (with a positive serum immunoglobulin E (IgE) defined as a value ≥ 0.35 kU/L). OR 2 minor critieria:
  • Wheezing unrelated to colds.
  • Peripheral blood eosinophilia ≥ 4%.
  • Allergic sensitization to milk, eggs, or peanuts (defined by serum specific IgE > 0.35 kU/L.
• Blood eosinophils ≥ 300 cells/µL at screening.
• Parent(s)/caregiver(s)/legal guardian(s) willing and able to comply with clinic visits and study-related procedures.
• Parent(s)/caregiver(s)/legal guardian(s) able to understand the study requirements. Participants/parent(s)/caregiver(s)/legal guardian(s), as appropriate, must be able to understand and complete study-related questionnaires.

Weight

• Body weight at screening and randomization > 5 kg and < 30 kg.

Informed Consent

• Parents or caregivers or legal guardian capable of giving signed informed consent as described in Appendix 1 (Section 10.1.3) of the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria: 

Medical conditions

• Severe asthma with the need for chronic oral/systemic corticosteroid use ( > th continuous) at the time of screening enrollment.
• History of a systemic hypersensitivity reaction or anaphylaxis to dupilumab or any other biologic therapy, including any excipient.
• History of prematurity ( < 34 weeks gestation).
• Any other chronic lung disease that would impair lung function (eg, cystic fibrosis, broncopulmonary dysplasia) or chronic lung disease of prematurity or need for oxygen for more than 5 days in the neonatal period.
• History of life-threatening asthma (eg, requiring intubation).
• Other significant medical conditions including but not limited to: major congenital anomalies, chest wall deformities such as spondylocostal dysplasia, cystic fibrosis, interstitial pulmonary disease, bronchopulmonary dysplasia, thoracic surgery, immunodeficiency (primary or secondary), seizure disorders.
• Severe concomitant illness(es) that, in the Investigator’s judgment, would adversely affect the participant’s participation in the study. Examples include but are not limited to participants with short life expectancy, participants with uncontrolled diabetes (hemoglobin A1c ≥ 9%), severe renal, hepato-biliary, neurological conditions autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc), other severe endocrinological, gastrointestinal, metabolic, pulmonary, psychiatric, or lymphatic diseases. The specific justification for participants excluded under this criterion will be noted in study documents (chart notes, case report forms [CRFs], etc).
• Participants with active tuberculosis (TB) or non-tuberculous mycobacterial infection, or a history of incompletely treated TB will be excluded from the study unless it is well documented by a specialist that the participant has been adequately treated and can now start treatment with a biologic agent, in the medical judgment of the Investigator and/or infectious disease specialist. Tuberculosis testing will be performed on a country-by-country basis, according to local guidelines if required by regulatory authorities or ethics boards.
• History of malignancy of any kind.
• Diagnosed with, suspected of, or at high risk of endoparasitic infection (helminths); and/or use of antiparasitic drug within 2 weeks before Screening Visit (Visit 1) or during the Screening period.
• Known or suspected immunodeficiency, including invasive opportunistic infections (eg, TB, histoplasmosis, listeriosis coccidiomycosis, pneumocystosis, aspergillosis), despite infection resolution; or otherwise, recurrent infections of abnormal frequency or prolonged duration suggesting an immune-compromised status, as judged by the Investigator.
• Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 2 weeks before the Screening Visit (Visit 1) or during the screening period.
• Participants with autoimmune disease or participants using immunosuppressive therapy for autoimmune disease (eg, juvenile idiopathic arthritis, inflammatory bowel disease, systemic lupus erythematosus, etc.).
• History of human immunodeficiency virus (HIV) infection or positive HIV serology at Visit 1.
• At any time: Participants with positive (or indeterminate) test for hepatitis B surface antigen (HBsAg), positive Immunoglobulin M (IgM) hepatitis B core antibody (HBcAb); positive total HBcAb confirmed by positive total hepatitis B virus DNA (HBV DNA); positive hepatitis C virus antibody (HCVAb) confirmed by positive hepatitis C virus RNA (HCV RNA).
• Abnormal laboratory values at screening:
  • Creatine phosphokinase (CPK) > 3 ULN; or,
  • Platelets < 100 000 cells/mm^3 .
  • Eosinophils ≥ 1500 cells/µL.

Prior/concomitant therapy

• Need for systemic corticosteroids or a hospitalization for respiratory symptoms within 4 weeks prior to Screening and during Screening period.
• Non-compliance with the use of mandatory background therapy during the Screening period, as defined by < 80% of the total number of prescribed background medications for this period. Compliance is verified based on background medication use recorded by caregivers in the participant eDiary.
• Any biologic therapy/immunosuppressant to treat inflammatory disease, allergic disease, or autoimmune disease (eg, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus as well as other diseases) within 2 months or 5 half-lives prior to Visit 1, whichever is longer.
• Initiation of allergen immunotherapy within 3 months prior to Visit 1 or dose change from 1 month prior to Visit 1 or a plan to begin allergen immunotherapy or to change its dose during the screening period or the randomized treatment period.
• Exposure to another investigational antibody within a time-period prior to Visit 1 that is less than 5 half-lives of the antibody. In case the half-life is not known, then the minimum interval since exposure to the prior investigational antibody is 6 months. The minimum interval since exposure to any other (non-antibody) investigational study medication is 30 days prior to Visit 1.
• Either intravenous immunoglobulin therapy within 30 days prior to Screening Visit (Visit 1).
• Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit or planned during the study.
  • NOTE: For participants who have vaccination with live attenuated vaccines (LAV) planned during the course of the study (based on national vaccination schedule/local guidelines), it will be determined, after consultation with a pediatrician, whether the administration of the vaccine can be postponed until after the EOS, or preponed to before the first IMP administration, without compromising the health of the participant:
    • Participants for whom administration of live (attenuated) vaccine can be safely postponed would be eligible to enroll into the study.
    • Participants who have their vaccination preponed can enroll in the study only after a gap of 4 weeks following administration of the vaccine.

Prior/concurrent clinical study experience

• Participants who have previously been treated with dupilumab.

Other exclusion criteria

• Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
• Any country-related specific regulation that would prevent the participant from entering the study – see Appendix Section 10.8 of the protocol (country-specific requirements).
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
• Participant’s parent(s)/caregiver(s)/legal guardian(s) is related to the Investigator or are employees of the clinical study center or other individuals directly involved in the conduct of the study, or immediate family members of such individuals (in conjunction with Section 1.61 of the ICH-GCP Ordinance E6).
• Any specific situation during study implementation/course that may raise ethics considerations.
• 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.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/3/23. Questions regarding updates should be directed to the study team contact.