A Study to Evaluate the Efficacy of MEDI8968 in Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of MEDI8968 on the rate of moderate or severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in adult subjects with symptomatic, moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease - GOLD stage II-IV) receiving standard maintenance therapy for the underlying disease condition.

Detailed Description
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A Phase 2 double-blind, placebo-controlled study to evaluate the efficacy of MEDI8968 in Chronic Obstructive Pulmonary Disease. The study will have a screening phase of 23 days, treatment phase from Week 1 to 53 and follow-up phase from Week 53 to 69. Participants will receive either MEDI8968 600 milligram (mg) as intravenous (IV) infusion on Day 1 followed by 300 mg injection subcutaneously (SC) every 4 weeks up to Week 53 or matching placebo in the same fashion. Participants will primarily be assessed for incidence rate of moderate or severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Safety will be monitored throughout the study.

Official Title
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A Phase 2 Double-blind, Placebo-controlled Study to Evaluate the Efficacy of MEDI8968 in Chronic Obstructive Pulmonary Disease

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Biological: MEDI8968 600 mg IV, 300 mg SC
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 45 through 75 years Predicted (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage II, III, and IV) at Screening History of previous acute exacerbations of chronic obstructive pulmonary disease (AECOPD) 12 months prior to Screening Clinically stable and free from an AECOPD for 8 weeks prior to Day 1 Current smoker or ex-smoker with a tobacco history of more than or equal to (>=) 10 pack-years. Exclusion Criteria: Past or present disease or disorder, Significant or unstable ischemic heart disease etc Known history of allergy or reaction to any component of the investigational manufacturing product (IMP) Past or current malignancy within the past 5 years Subjects have had a chest x-ray or Computed Tomography (CT) scan suggestive of malignancy or tuberculosis (TB). Use of immunosuppressive medication receipt of any biologic agent.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53. | Other: Placebo<br>* Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.<br>|
| Experimental: MEDI8968 600 mg IV, 300 mg SC<br>MEDI8968 600 milligram (mg) as intravenous (IV) infusion on Day 1 followed by 300 mg injection subcutaneously (SC) every 4 weeks up to Week 53. | Biological: MEDI8968 600 mg IV, 300 mg SC<br>* MEDI8968 600 mg as IV infusion on Day 1 followed by 300 mg injection SC every 4 weeks up to Week 53.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. The severity of an AECOPD is defined as: Moderate exacerbations require treatment with systemic corticosteroids, and or antibiotics. Severe exacerbations require hospitalization. The AECOPD rate was analyzed using a Poisson Regression model adjusted for over dispersion with number of exacerbations as the outcome and the log of follow-up time as an offset variable, with covariates for treatment group (MEDI8986, placebo), background maintenance therapy and previous exacerbations. Mean exacerbations were presented as number of exacerbations/year. | Day 1 up to 393 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Rate of Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. Severe exacerbations require hospitalization. The AECOPD rate was analyzed using a Poisson Regression model adjusted for over dispersion with number of exacerbations as the outcome and the log of follow-up time as an offset variable, with covariates for treatment group (MEDI8986, placebo), background maintenance therapy and previous exacerbations. Mean exacerbations were presented as number of exacerbations/year. | Day 1 up to 393 | 
| Time to First Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | Time to first worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. The severity of an AECOPD is defined as: Mild exacerbations require treatment with an increase in usual therapy, e.g., increase use of short acting bronchodilators. Moderate exacerbations require treatment with systemic corticosteroids, and or antibiotics. Severe exacerbations require hospitalization. | Day 1 up to 393 | 
| Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Subscales Scores at Week 53 | The SGRQ is a health related quality of life questionnaire consisting of 40 items in three domains: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response has a unique empirically derived weight where lowest possible weight is zero and the highest is 100. The total score and domain score are derived from the relevant items and converted to a score of 0 to 100 with a higher score indicating poorer health status. | Baseline and Week 53 | 
| Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | The SGRQ is a health related quality of life questionnaire consisting of 40 items in three domains: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response has a unique empirically derived weight where lowest possible weight is zero and the highest is 100. The total score and domain score are derived from the relevant items and converted to a score of 0 to 100 with a higher score indicating poorer health status. A 4-point change in total score demonstrates a clinically meaningful change, while an 8-point change and a 12-point change are interpreted as a moderate and large change in health status, respectively. | Week 53 | 
| Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score at Week 53 | The BODE index is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the modified medical research council (MMRC) dyspnea scale and the 6-minute walk test. The MMRC dyspnea scale is a 5-point scale that measures the level of dyspnea (trouble breathing) experienced by participants where score range is 0 (none) to 4 (very severe). BODE score is derived into a score range of 0 (healthy) to 10 (severe COPD). | Baseline and Week 53 | 
| Percentage of Participants With Improvement in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score | The BODE index is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the modified medical research council (MMRC) dyspnea scale and the 6-minute walk test. The MMRC dyspnea scale is a 5-point scale that measures the level of dyspnea (trouble breathing) experienced by participants where score range is 0 (none) to 4 (very severe). BODE score is derived into a score range of 0 (healthy) to 10 (severe COPD). Negative change score signifies improvement compared to baseline. Number of participants with improvement in BODE score compared to baseline were reported. | Baseline and Week 53 | 
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Week 69 that were absent before treatment or that worsened relative to pre-treatment state. TEAEs reported below included both SAEs and non-serious AEs. | Day 1 up to Week 69 | 
| Observed Serum Concentrations of MEDI8968 |  | Pre-dose (Baseline), Post-dose on Week 53 | 
| Number of Participants Exhibiting Anti-Drug Antibodies for MEDI8968 at Any Visit | Anti-drug antibodies for MEDI8968 were analyzed for participants who received placebo or MEDI8968 as per planned analysis. | Day 1 up to Week 69 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD), MEDI8968