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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI8968 600 mg IV, 300 mg SC
Placebo
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring Chronic Obstructive Pulmonary Disease (COPD), MEDI8968

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

MEDI8968 600 mg IV, 300 mg SC

Arm Description

Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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).
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.
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.
Observed Serum Concentrations of MEDI8968
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.

Full Information

First Posted
October 6, 2011
Last Updated
November 30, 2016
Sponsor
MedImmune LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01448850
Brief Title
A Study to Evaluate the Efficacy of MEDI8968 in Chronic Obstructive Pulmonary Disease
Acronym
SPRING
Official Title
A Phase 2 Double-blind, Placebo-controlled Study to Evaluate the Efficacy of MEDI8968 in Chronic Obstructive Pulmonary Disease
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
Chronic Obstructive Pulmonary Disease (COPD), MEDI8968

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
464 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.
Arm Title
MEDI8968 600 mg IV, 300 mg SC
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
MEDI8968 600 mg IV, 300 mg SC
Intervention Description
MEDI8968 600 mg as IV infusion on Day 1 followed by 300 mg injection SC every 4 weeks up to Week 53.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.
Primary Outcome Measure Information:
Title
Mean Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Secondary Outcome Measure Information:
Title
Mean Rate of Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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 Frame
Day 1 up to 393
Title
Time to First Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Title
Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Subscales Scores at Week 53
Description
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.
Time Frame
Baseline and Week 53
Title
Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score
Description
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.
Time Frame
Week 53
Title
Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score at Week 53
Description
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).
Time Frame
Baseline and Week 53
Title
Percentage of Participants With Improvement in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Score
Description
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.
Time Frame
Baseline and Week 53
Title
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
Day 1 up to Week 69
Title
Observed Serum Concentrations of MEDI8968
Time Frame
Pre-dose (Baseline), Post-dose on Week 53
Title
Number of Participants Exhibiting Anti-Drug Antibodies for MEDI8968 at Any Visit
Description
Anti-drug antibodies for MEDI8968 were analyzed for participants who received placebo or MEDI8968 as per planned analysis.
Time Frame
Day 1 up to Week 69

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rene Van Der Merwe, MBChB, MFPM
Organizational Affiliation
MedImmune Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Peoria
State/Province
Arizona
Country
United States
Facility Name
Research Site
City
Clearwater
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Duluth
State/Province
Georgia
Country
United States
Facility Name
Research Site
City
Auburn
State/Province
Maine
Country
United States
Facility Name
Research Site
City
Buffalo
State/Province
New York
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
Country
United States
Facility Name
Research Site
City
Spartanburg
State/Province
South Carolina
Country
United States
Facility Name
Research Site
City
Boerne
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
Research Site
City
Plovdiv
Country
Bulgaria
Facility Name
Research Site
City
Ruse
Country
Bulgaria
Facility Name
Research Site
City
Sofia
Country
Bulgaria
Facility Name
Research Site
City
Stara Zagora
Country
Bulgaria
Facility Name
Research Site
City
Veliko Tarnovo
Country
Bulgaria
Facility Name
Research Site
City
Brno
Country
Czech Republic
Facility Name
Research Site
City
Jindrichuv Hradec
Country
Czech Republic
Facility Name
Research Site
City
Karlovy Vary
Country
Czech Republic
Facility Name
Research Site
City
Plzen
Country
Czech Republic
Facility Name
Research Site
City
Praha 10
Country
Czech Republic
Facility Name
Research Site
City
Strakonice
Country
Czech Republic
Facility Name
Research Site
City
Balassagyarmat
Country
Hungary
Facility Name
Research Site
City
Budapest
Country
Hungary
Facility Name
Research Site
City
Farkasgyepü
Country
Hungary
Facility Name
Research Site
City
Komarom
Country
Hungary
Facility Name
Research Site
City
Mateszalka
Country
Hungary
Facility Name
Research Site
City
Matrahaza
Country
Hungary
Facility Name
Research Site
City
Mosonmagyarovar
Country
Hungary
Facility Name
Research Site
City
Nagykanizsa
Country
Hungary
Facility Name
Research Site
City
Szikszo
Country
Hungary
Facility Name
Research Site
City
Tatabanya
Country
Hungary
Facility Name
Research Site
City
Torokbalint
Country
Hungary
Facility Name
Research Site
City
Daugavpils
Country
Latvia
Facility Name
Research Site
City
Riga
Country
Latvia
Facility Name
Research Site
City
Kaunas
Country
Lithuania
Facility Name
Research Site
City
Klaipeda
Country
Lithuania
Facility Name
Research Site
City
Vilnius
Country
Lithuania
Facility Name
Research Site
City
Iloilo City
Country
Philippines
Facility Name
Research Site
City
Lipa City
Country
Philippines
Facility Name
Research Site
City
Quezon City
Country
Philippines
Facility Name
Research Site
City
Bialystok
Country
Poland
Facility Name
Research Site
City
Gdansk
Country
Poland
Facility Name
Research Site
City
Krakow
Country
Poland
Facility Name
Research Site
City
Lodz
Country
Poland
Facility Name
Research Site
City
Oswiecim
Country
Poland
Facility Name
Research Site
City
Poznan
Country
Poland
Facility Name
Research Site
City
Wroclaw
Country
Poland
Facility Name
Research Site
City
Zgierz
Country
Poland
Facility Name
Research Site
City
Ivano-Frankivsk
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
Country
Ukraine
Facility Name
Research Site
City
Kyiv
Country
Ukraine
Facility Name
Research Site
City
Odessa
Country
Ukraine
Facility Name
Research Site
City
Poltava
Country
Ukraine
Facility Name
Research Site
City
Simferopol
Country
Ukraine
Facility Name
Research Site
City
Vinnytsya
Country
Ukraine
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
Newcastle upon Tyne
Country
United Kingdom
Facility Name
Research Site
City
Wolverhampton
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28793896
Citation
Calverley PMA, Sethi S, Dawson M, Ward CK, Finch DK, Penney M, Newbold P, van der Merwe R. A randomised, placebo-controlled trial of anti-interleukin-1 receptor 1 monoclonal antibody MEDI8968 in chronic obstructive pulmonary disease. Respir Res. 2017 Aug 9;18(1):153. doi: 10.1186/s12931-017-0633-7.
Results Reference
derived

Learn more about this trial

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

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