Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: MEDI3506; Placebo
Intervention description: Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2; Participants will receive multiple doses of placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 250.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: MEDI3506; lung function; IL-33; inflammation

Summary:

      Study D9181C00001 is a Phase II, randomised, double-blind, placebo-controlled, parallel
      group, proof of concept study to evaluate the efficacy, safety, pharmacokinetics (PK) and
      immunogenicity of MEDI3506 in adult participants with uncontrolled moderate to severe asthma
      on standard of care (SOC). Up to approximately 80 sites globally will participate in this
      study.

      Approximately 228 participants will be randomized to 3 treatment groups in a 1:1:1 ratio to
      receive MEDI3506 dose 1, MEDI3506 dose 2, or placebo.
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Aged 18 to < 65 years of age

          -  Physician-diagnosed asthma of early onset, defined as development of asthma before the
             age of 25 years.

          -  History of ≥ 1 asthma exacerbation in previous 24 months

          -  Treated with medium to high dose ICS defined as total daily dose of > 250 g
             fluticasone dry powder or equivalent, for at least 12 months and on a stable dose for
             ≥ 3 months.

          -  Stable LABA therapy for ≥ 3 months.

          -  An ACQ-6 score ≥ 1.5.

          -  Morning pre-BD FEV1 ≥ 40% predicted normal and > 1 L.

          -  Morning pre-BD FEV1 < 85% predicted normal.

          -  Participants with documented evidence of asthma as demonstrated by either:

          -  BD reversibility, within 12 months, or at screening, or

          -  Positive methacholine challenge test within 12 months.

          -  Bodyweight ≥ 40 kg and BMI < 40 kg/m2.

          -  For female participants, a negative pregnancy test.

          -  Abide by contraception requirements for males and females

          -  Provide informed consent

        EXCLUSION CRITERIA

          -  Participants with a positive diagnostic nucleic acid test for SARS-CoV-2.

          -  Participants with a significant COVID-19 illness within 6 months of enrolment:

          -  Participants with a recent history of, or who have a positive test for, infective
             hepatitis or unexplained jaundice, or participants who have been treated for hepatitis
             B, hepatitis C, or HIV.

          -  Evidence of active or latent TB:

          -  An LVEF < 45% measured by echocardiogram during screening.

          -  A family history of heart failure.

          -  Current smokers or recent ex-smokers i.e., have quit e cigarettes or other inhaled
             tobacco products ≤ 6 months prior to SV1.

          -  Ex-smokers with a total smoking history of > 10 pack years.

          -  As judged by the investigator, any evidence of any active medical or psychiatric
             condition or other reason (prior to randomisation) that in the investigator's opinion
             makes it undesirable for the participant to participate in the study.

          -  Any clinically important pulmonary disease other than asthma.

          -  Any other clinically relevant abnormal findings on physical examination or laboratory
             testing, that in the opinion of the investigator or medical monitor might compromise
             the safety of the participant in the study or interfere with evaluation of the study
             intervention.

          -  A known history of severe reaction to any medication including biologic agents or
             human gamma globulin therapy.

          -  History of, or a reason to believe, a participant has a history of, drug or alcohol
             abuse within the past 2 years.

          -  Current diagnosis of cancer.

          -  History of cancer, except if treated with apparent success with curative therapy
             (response duration of > 5 years).

          -  History of allogeneic bone marrow transplant.

          -  A helminth parasitic infection diagnosed within 6 months prior to SV4 (randomisation)
             that has not been treated, or has not responded to SOC therapy.

          -  An asthma exacerbation within 8 weeks.

          -  Receiving any prohibited concomitant medications or therapies as specified in the
             protocol:

        Known history of allergy or reaction to any component of the study intervention
        formulation, including hereditary fructose intolerance.