Study to Assess the Efficacy and Safety of MEDI3506 in Adults With Uncontrolled Moderate-to-severe Asthma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of MEDI3506 in Adult Participants With Uncontrolled Moderate-to-severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Biological: MEDI3506
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI3506 Dose 1<br>Approximately 76 participants will be randomized to this arm to receive the higher dose of MEDI3506 | Biological: MEDI3506<br>* Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2<br>|
| Experimental: MEDI3506 Dose 2<br>Approximately 76 participants will be randomized to this arm to receive the lower dose of MEDI3506 | Biological: MEDI3506<br>* Participants will receive multiple doses of MEDI3506 at dose level 1 or dose level 2<br>|
| Placebo Comparator: Placebo<br>Approximately 76 participants will be randomized to this arm. Participants in this group will receive the placebo. | Drug: Placebo<br>* Participants will receive multiple doses of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 16 in pre-BD FEV1 (L) | To assess the effect of MEDI3506 compared with placebo on lung function (pre-BD FEV1 [L]) between baseline and week 16, in adult participants with uncontrolled moderate-to-severe asthma. | From Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum MEDI3506 concentration-time profiles from Study Day 1 until Study Day 169 | MEDI3506 serum concentrations by treatment [ Time Frame: from study Day 1 to Study Day 169] Serum samples will be collected on Day 1(predose), Day 8, as a trough sample collected prior to the next dose administration (on Days 29,57, 85 and 113) and two additional timepoints after last dose (Days 141 and 161) | from Study Day 1 to Study Day 169 for a total of 24 weeks | 
| ADA during the intervention and follow-up periods | 1. To assess immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to severe asthma determined by prevalence of antidrug antibodies (ADA) [ Time Frame: from study Day 1 to Study Day 169] Immunogenicity prevalence measured as number of participants with ADA positive at baseline and/or post-baseline 1. To assess immunogenicity of MEDI3506 in adult participants with uncontrolled moderate-to severe asthma determined by incidence of antidrug antibodies (ADA)[ Time Frame: from study Day 1 to Study Day 169] Immunogenicity incidence measured as number of participants with positive treatment emergent ADA | from Study Day 1 to Study Day 169 for a total of 24 weeks | 
| Change from baseline to Week 16 in ACQ-6 score. | To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control. | Baseline to Week 16 | 
| Proportion of participants with a decrease in ACQ-6 score of ≥ 0.5 from baseline to Week 16 | To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control. | Baseline to Week 16 | 
| Proportion of participants achieving ACQ-6 well controlled status (defined as ACQ-6 score ≤ 0.75 at Week 16) | To assess the effect of MEDI3506 compared with placebo on asthma control in adult participants with uncontrolled moderate-to-severe asthma. ACQ-6 = Asthma Control Questionnaire 6. Minimum score = 0. Maximum score = 6. A higher score indicates worse asthma control. | Week 16 | 
| Change from baseline in SGRQ at Week 16 | To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. SGRQ = St George's Respiratory Questionnaire. Minimum score = 0. Maximum score = 100. A higher score indicates a worse health status. | Baseline to Week 16 | 
| Proportion of participants with a decrease in SGRQ total score of ≥ 4 points from baseline to Week 16. | To assess the effect of MEDI3506 compared with placebo on health status in adult participants with uncontrolled moderate-to-severe asthma. SGRQ = St George's Respiratory Questionnaire. Minimum score = 0. Maximum score = 100. A higher score indicates a worse health status. | Baseline to Week 16 | 
| Change from baseline to Weeks 8 and 16 in post-BD FEV1 (L) | To further assess the effect of MEDI3506 compared with placebo on lung function (post-BD FEV1 [L]) between baseline and weeks 8 and 16, in adult participants with uncontrolled moderate-to-severe asthma | From baseline to Weeks 8 and 16 | 
| Time to first CompEx event based on the period from baseline to Week 16 | To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma | Baseline to Week 16 | 
| Annualised CompEx event rate | To assess the effect of MEDI3506 compared with placebo on CompEx in adult participants with uncontrolled moderate-to-severe asthma. | Baseline to Week 16 | 
| Percent change from baseline to Week 16 in concentration of FeNO in exhaled breath | To assess the effect of MEDI3506 compared with placebo on concentration of FeNO in adult participants with uncontrolled moderate-to-severe asthma | From baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MEDI3506, lung function, IL-33, inflammation