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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: Placebo; Biological: MEDI8968 600 mg IV, 300 mg SC

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.

• Study Type: Interventional
• Enrollment (Actual): 464
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria
    • Research Site
  • Ruse, Bulgaria
    • Research Site
  • Sofia, Bulgaria
    • Research Site
  • Stara Zagora, Bulgaria
    • Research Site
  • Veliko Tarnovo, Bulgaria
    • Research Site
• Czech Republic
  • Brno, Czech Republic
    • Research Site
  • Jindrichuv Hradec, Czech Republic
    • Research Site
  • Karlovy Vary, Czech Republic
    • Research Site
  • Plzen, Czech Republic
    • Research Site
  • Praha 10, Czech Republic
    • Research Site
  • Strakonice, Czech Republic
    • Research Site
• Hungary
  • Balassagyarmat, Hungary
    • Research Site
  • Budapest, Hungary
    • Research Site
  • Farkasgyepü, Hungary
    • Research Site
  • Komarom, Hungary
    • Research Site
  • Mateszalka, Hungary
    • Research Site
  • Matrahaza, Hungary
    • Research Site
  • Mosonmagyarovar, Hungary
    • Research Site
  • Nagykanizsa, Hungary
    • Research Site
  • Szikszo, Hungary
    • Research Site
  • Tatabanya, Hungary
    • Research Site
  • Torokbalint, Hungary
    • Research Site
• Latvia
  • Daugavpils, Latvia
    • Research Site
  • Riga, Latvia
    • Research Site
• Lithuania
  • Kaunas, Lithuania
    • Research Site
  • Klaipeda, Lithuania
    • Research Site
  • Vilnius, Lithuania
    • Research Site
• Philippines
  • Iloilo City, Philippines
    • Research Site
  • Lipa City, Philippines
    • Research Site
  • Quezon City, Philippines
    • Research Site
• Poland
  • Bialystok, Poland
    • Research Site
  • Gdansk, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Oswiecim, Poland
    • Research Site
  • Poznan, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
  • Zgierz, Poland
    • Research Site
• Ukraine
  • Ivano-Frankivsk, Ukraine
    • Research Site
  • Kharkiv, Ukraine
    • Research Site
  • Kyiv, Ukraine
    • Research Site
  • Odessa, Ukraine
    • Research Site
  • Poltava, Ukraine
    • Research Site
  • Simferopol, Ukraine
    • Research Site
  • Vinnytsya, Ukraine
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom
    • Research Site
  • Newcastle upon Tyne, United Kingdom
    • Research Site
  • Wolverhampton, United Kingdom
    • Research Site
• United States
  • Arizona
    • Peoria, Arizona, United States
      • Research Site
  • Florida
    • Clearwater, Florida, United States
      • Research Site
  • Georgia
    • Duluth, Georgia, United States
      • Research Site
  • Maine
    • Auburn, Maine, United States
      • Research Site
  • New York
    • Buffalo, New York, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States
      • Research Site
    • Spartanburg, South Carolina, United States
      • Research Site
  • Texas
    • Boerne, Texas, United States
      • Research Site
  • Virginia
    • Richmond, Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.	Other: Placebo; Placebo matched to MEDI8968 as IV infusion on Day 1 followed by SC injection every 4 weeks up to Week 53.
Experimental: 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.	Biological: MEDI8968 600 mg IV, 300 mg SC; MEDI8968 600 mg as IV infusion on Day 1 followed by 300 mg injection SC every 4 weeks up to Week 53.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Rene Van Der Merwe, MBChB, MFPM, MedImmune Ltd

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (Estimate): October 7, 2011

Study Record Updates

• Last Update Posted (Estimate): January 30, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease (COPD); MEDI8968
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CD-RI-MEDI8968-1103