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

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Other: Placebo
Biological: MEDI8968 600 mg IV, 300 mg SC

Registration Number: NCT01448850

Lead Sponsor: MedImmune LLC

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 464

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.
MEDI8968 600 mg IV, 300 mg SC	MEDI8968 600 mg IV, 300 mg SC	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.

Primary Outcome Measures

Name	Time	Method
Mean Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)	Day 1 up to 393	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.

Secondary Outcome Measures

Name	Time	Method
Mean Rate of Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)	Day 1 up to 393	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.
Time to First Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)	Day 1 up to 393	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.
Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score	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. 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.
Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Subscales Scores at Week 53	Baseline and 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.
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	Day 1 up to Week 69	Anti-drug antibodies for MEDI8968 were analyzed for participants who received placebo or MEDI8968 as per planned analysis.
Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score at Week 53	Baseline and 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).
Percentage of Participants With Improvement in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score	Baseline and 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). Negative change score signifies improvement compared to baseline. Number of participants with improvement in BODE score compared to baseline were reported.
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	Day 1 up to Week 69	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.