Clinical trial NCT01006616: Long-Term Study of the Effects of Navarixin (SCH 527123, MK-7123) in Participants With Moderate to Severe COPD (MK-7123-019)
Official title: A 2-Year, Dose Range-Finding, Adaptive-Design Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COPD
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-11-03
Enrollment: 616
Sex: ALL
Minimum age (years): 41
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Neutrophils are thought to play an important role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Navarixin (SCH 527123, MK-7123) is an antagonist of the cysteine-X-cysteine chemokine receptor 2 (CXCR2) and is thought to reduce neutrophil migration to the diseased lung. It is theorized that reducing neutrophil migration to the diseased lung will improve a participant's symptoms and the natural history of the disease.

The study will consist of a 2-week screening period followed by a 2-year (104-week) double-blind treatment period. The 2-year Treatment Period will be made up of two phases: a 26-week (6-month) dose range-finding phase with 3 active arms and 1 placebo arm (Period 1), followed by a 78-week (18-month) long-term safety and efficacy phase (Period 2). Participants participating in the original 6-month study (Period 1) may elect not to continue into the 18-month extension study (Period 2).

Hypothesis: navarixin, 50 mg, or the highest remaining dose if the 50-mg dose is discontinued, is superior to placebo with respect to improving airflow.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of COPD for at least 2 years based on American Thoracic Society/European Respiratory Society (ATS/ERS) current guidelines or symptoms consistent with COPD for at least 2 years.
* \>40 to \<=75 years of age, of either sex, and of any race.
* No exacerbation or respiratory infection in the past 6 weeks.
* Smoker or ex-smoker with more than 10 pack-year history.

Exclusion Criteria:

* Diagnosis of asthma or other clinically relevant lung disease (other than COPD), i.e., sarcoidosis, tuberculosis, pulmonary fibrosis, severe bronchiectasis, or lung cancer.
* Significant X-ray findings.
* Use of supplemental oxygen for \>12 hours/day.

Primary outcomes:
measure: Change From Baseline in Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Period 1)
timeFrame: Baseline and Week 26
measure: Percentage of Participants With an Adverse Event (AE) Related to a Blood Absolute Neutrophil Count (ANC) of Less Than 1.5x10^9 Cells/L
timeFrame: Up to 104 weeks
Secondary outcomes:
measure: Change From Baseline in Post-bronchodilator FEV1 (Period 2)
timeFrame: Baseline and Week 52, Week 104
measure: Number of Participants With a Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
timeFrame: Up to 26 , 52 and 104 weeks
measure: Percentage of Participants With a Moderate to Severe COPD Exacerbation
timeFrame: Up to 26, 52 and 104 weeks
measure: Total Exacerbations of Chronic Pulmonary Disease Tool-Patient-Recorded Outcome (EXACT-PRO) Questionnaire Score
timeFrame: At 26, 52 and 104 weeks
measure: Induced Sputum Absolute Neutrophil Counts
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Change From Baseline in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Distance Walked in 6 Minutes (6-Minute Walk Test)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Pre-bronchodilator FEV1
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity (FEF25%-75%) Test
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Post-bronchodilator Forced Vital Capacity (FVC)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Functional Residual Capacity (FRC)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Total Lung Capacity (TLC)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Inspiratory Capacity (IC)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Morning Peak Expiratory Flow (PEF)
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Body-Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Index Score
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Modified Medical Research Council (MMRC) Dyspnea Score
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Sputum Inflammatory Marker Levels: Interleukin 8 (IL-8)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Sputum Inflammatory Marker Levels: Myeloperoxidase (MPO)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Sputum Inflammatory Marker Levels: Sputum Neutrophil Elastase
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Sputum Inflammatory Marker Levels: Matrix Metallopeptidase-9 (MMP-9)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: High-sensitivity C-reactive Protein (Hs-CRP)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: Fibrinogen
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: Myeloperoxidase (MPO)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: Matrix Metallopeptidase-9 (MMP-9)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: Plasma Neutrophil Elastase
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Plasma Inflammatory Biomarker Levels: Epithelial Cell-Derived Neutrophil Activating Peptide 78 (ENA-78)
timeFrame: Baseline, Week 26, Week 52, Week 104
measure: Change From Baseline in Pre- and Post-6-Minute-Walk-Test Borg Scale Score
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Change From Baseline in Percent of Arterial Oxygen Saturation Measured by Pulse Oximetry Before and After the 6-Minute Walk Test
timeFrame: Baseline and Week 26, Week 52, Week 104
measure: Percentage of Participants Who Experienced an AE Related to Respiratory Infection
timeFrame: Up to 26 , 52 and 104 weeks
measure: Percentage of Participants Who Experienced an AE Related to Any Type of Infection
timeFrame: Up to 26 , 52 and 104 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Rennard SI, Dale DC, Donohue JF, Kanniess F, Magnussen H, Sutherland ER, Watz H, Lu S, Stryszak P, Rosenberg E, Staudinger H. CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2015 May 1;191(9):1001-11. doi: 10.1164/rccm.201405-0992OC.