Effect of Ensifentrine (MK-5884/RPL554) on Sputum Markers of Inflammation in Chronic Obstructive Pulmonary Disease (COPD) (MK-5884-023/RPL554-CO-207)
A Randomized, Double-Blind, Placebo-Controlled, Two-period Cross-over Study of the Effect of Ensifentrine on Sputum Markers of Inflammation in Subjects With COPD
Researchers are looking for new ways to treat chronic obstructive pulmonary disease (COPD). COPD is a long-lasting swelling of the airways that makes it hard to breathe. Researchers want to learn if a trial medicine called ensifentrine can help treat sputum caused by COPD. In this trial, researchers will compare a trial medicine called ensifentrine to a placebo. A placebo looks like the trial medicine but has no medicine in it. Using a placebo helps researchers better understand the effects of a trial medicine.
The goal of this trial is to learn about the effect of ensifentrine on a substance found in mucus (sputum) from the lungs that may be a sign of inflammation in participants with COPD.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
Alabama
-
Birmingham, Alabama, Forente stater, 35205
- University of Alabama at Birmingham
-
-
Michigan
-
Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Forente stater, 15213
- University of Pittsburgh Medical Center
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Participants with a history of cigarette smoking ≥10 pack years and an established clinical history of chronic obstructive pulmonary disease (COPD) as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD. Number of pack-years = [number of cigarettes per day/20] × number of years smoked [e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]
- COPD Severity: Pre- and Post-albuterol/salbutamol Forced expiratory volume in 1 second/Forced vital capacity (FEV1/FVC) ratio of <0.70; Post-albuterol/salbutamol FEV1 ≥30 % and ≤80% of predicted normal calculated using the National Health and Nutrition Examination Survey III
- Regular use of bronchodilator COPD therapy, in any form (e.g., [Long-acting muscarinic antagonist] LAMA, [Long-acting β2-agonist] LABA, LAMA+LABA, LAMA+LABA+ [Inhaled corticosteroid(s)] ICS), for at least 4 weeks prior to Screening and agrees to use study supplied COPD Maintenance Therapy once daily through the final study visit
- Capable of using the jet nebulizer correctly and complying with all study restrictions and procedures
- Ability to perform acceptable spirometry in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
- Ability to produce sputum samples during the induced sputum procedure
Exclusion Criteria:
- Any clinically diagnosed lung disease other than COPD such as current asthma, diffuse interstitial lung diseases, cystic fibrosis, or clinically significant bronchiectasis as determined by the Investigator
- Hospitalizations for COPD exacerbation, pneumonia, or other respiratory infection in the 12 weeks prior to Screening.
- Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- Human immunodeficiency virus (HIV) infection or other immunodeficiency
- History of cancer within the last 5 years, except for well-treated basal cell carcinoma and squamous cell carcinoma of the skin
- Any clinically significant 12-lead electrocardiogram abnormalities at screening or baseline, including corrected QT interval by Fridericia's correction method >450 ms for males or >480 ms for females or history of significant cardiac dysrhythmia, including long QT syndrome
- Known history of poor outcomes with sputum induction
- Known hypersensitivity to ensifentrine or other medications used in the study (e.g., albuterol or salmeterol)
- Not suitable for study supplied once daily COPD Maintenance Therapy per label warnings and contraindications
- Taking prohibited medication
- Prior receipt of Ohtuvayre or blinded nebulized study medication in an ensifentrine (RPL554) study. Note: Other ensifentrine formats (e.g., DPI, MPI) are not exclusionary
- Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical trial within 30 days prior to Screening
- Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical trial within 30 days prior to Screening
- Any other medical history, chronic uncontrolled diseases that the investigator considers clinically significant, examination or laboratory findings or reason that the Investigator considers makes the patient unsuitable to participate at Screening
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Crossover-oppdrag
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Ensifentrine Sequence 1
In treatment period 1 participants will receive 3 mg ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks followed by treatment period 2 during which participants will receive placebo matching ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks. Throughout treatment sequence 1 participants will receive LABA/LAMA background therapy. |
Ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer. Placebo matching ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer. Background treatment of LAMA/LABA administered per product approved label delivered by oral inhalation.
Andre navn:
|
|
Eksperimentell: Ensifentrine Sequence 2
In treatment period 1 participants will receive placebo matching ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks followed by treatment period 2 during which participants will receive 3 mg ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks. Throughout treatment sequence 2 participants will receive LABA/LAMA background therapy. |
Ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer. Placebo matching ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer. Background treatment of LAMA/LABA administered per product approved label delivered by oral inhalation.
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
The Absolute Change From Baseline in Sputum Neutrophil Cell Numbers
Tidsramme: Baseline and 8 Weeks
|
The Absolute change from baseline in sputum neutrophil cell numbers will be reported. |
Baseline and 8 Weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Absolute Change in Cell Numbers From Baseline in Sputum Cell Counts
Tidsramme: Baseline and 8 Weeks
|
Absolute change in cell numbers from baseline in sputum cell counts (eosinophils, basophils, macrophages, lymphocytes, total cells) will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Sputum Cell Counts
Tidsramme: Baseline and 8 Weeks
|
Percent change from baseline in sputum cell counts (neutrophils, eosinophils, basophils, macrophages, lymphocytes, and total cells) will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Cytokines
Tidsramme: Baseline and 8 Weeks
|
Percent Change From Baseline in Cytokines will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Proteases
Tidsramme: Baseline and 8 Weeks
|
Percent Change From Baseline in Proteases will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Markers of Inflammation
Tidsramme: Baseline and 8 Weeks
|
Percent Change From Baseline in Markers of Inflammation will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in FEV1 at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in FEV1 at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in FEV1 at 8 weeks during the treatment period (postdose) will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Forced Vital Capacity (FVC) at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in FVC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in FVC at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in FVC at 8 weeks during the treatment period (postdose) will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Residual Volume (RV) at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in RV at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in RV at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in RV at 8 weeks (postdose) during the treatment period will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Functional Residual Capacity (FRC) at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in FRC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in FRC at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in FRC at 8 weeks (postdose) during the treatment period will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Total Lung Capacity (TLC) at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in TLC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in TLC at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in TLC at 8 weeks (postdose) during the treatment period will be reported. |
Baseline and 8 Weeks
|
|
Number of Participants Who Experience One or More Adverse Events (AEs)
Tidsramme: Up to approximately 8 Weeks
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who experience one or more adverse events will be reported. |
Up to approximately 8 Weeks
|
|
Change From Baseline in Systolic Blood Pressure
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in systolic blood pressure will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Diastolic Blood Pressure
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in diastolic blood pressure will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Heart Rate
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in heart rate will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in QRS Duration
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in QRS duration will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in QTcF will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in QT Interval
Tidsramme: Baseline and 8 Weeks
|
Change from baseline for in QT interval will be reported. |
Baseline and 8 Weeks
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Change From Baseline in Absolute Blood Cell Counts at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change from baseline in absolute blood cell counts at 4 weeks will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in Cytokines at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change From Baseline in Cytokines at 4 Weeks will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in Proteases at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change From Baseline in Proteases at 4 Weeks will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in Markers of Inflammation at 4 Weeks
Tidsramme: Baseline and 4 Weeks
|
Change From Baseline in Markers of Inflammation at 4 Weeks will be reported. |
Baseline and 4 Weeks
|
|
Change From Baseline in Absolute Blood Cell Counts at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in absolute blood cell counts at 8 weeks will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Cytokines at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in cytokines at 8 weeks will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Proteases at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in proteases at 8 weeks will be reported. |
Baseline and 8 Weeks
|
|
Change From Baseline in Blood Markers of Inflammation at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Change from baseline in blood markers of inflammation at 8 weeks will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Sputum Acetylated Proline-Glycine-Proline (AcPGP) at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Percent change from baseline in sputum Acetylated Proline-Glycine-Proline (AcPGP) at 8 weeks will be reported. |
Baseline and 8 Weeks
|
|
Percent Change From Baseline in Sputum Proline-Glycine-Proline (PGP) at 8 Weeks
Tidsramme: Baseline and 8 Weeks
|
Percent change from baseline in sputum PGP at 8 weeks will be reported. |
Baseline and 8 Weeks
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Studieleder: Medical Director, Merck Sharp & Dohme LLC
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- RPL554-CO-207
- MK-5884-023 (Annen identifikator: MSD)
- RPL554-CO-207 (Annen identifikator: VeronaPharma)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .