COPDPhase 2NCT03937479
Study Investigating the Effect of 4 Doses of RPL554 Given in Addition to Tiotropium to Patients With COPD
A Phase 2 study of COPD, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 50 sites in United States.
Trial summary
The purpose of this study is to investigate the dose response of RPL554 in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE that are still symptomatic despite treatment with a stable background of tiotropium over 4 weeks of treatment. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- COPD
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 416 participants
- Where
- 50 sitesUnited States
- Study dates
- 1 May 2019to 15 Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- Male or female aged between 40 and 80 years inclusive, at the time of informed consent.
- Must agree to meet the following from the first dose up to 1 month after the last dose of study medication:
- If male:
- Not donate sperm
- Either: be sexually abstinent in accordance with a patient's usual and preferred lifestyle (but agree to abide by the contraception requirements below should their circumstances change)
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- Or: use a condom with all sexual partners. If the partner is of childbearing potential the condom must be used with spermicide and a second reliable form of contraception must also be used (e.g., diaphragm/cap with spermicide, established hormonal contraception, intra-uterine device)
- If female:
- be of non-childbearing potential or use a highly effective form of contraception
- Have a 12-lead ECG recording at Screening showing the following (and no changes in the pre-dose value at the first treatment deemed clinically significant by the Investigator):
- Heart rate between 45 and 90 beats per minute
- QT interval corrected for heart rate using Fridericia's formula (QTcF) ≤450 msec for males, and ≤ 470 msec for females
- QRS interval ≤ 120 msec
- No clinically significant abnormality including morphology (e.g., left bundle branch block, atrio-ventricular nodal dysfunction, ST segment abnormalities consistent with ischemia)
- Capable of complying with study restrictions and procedures, including ability to use the nebulizer correctly.
- Body mass index (BMI) between 18 and 35 kg/m2 (inclusive) with a minimum weight of 45 kg.
- COPD diagnosis: Patients with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli and MacNee, 2004) with symptoms compatible with COPD for at least 1 year prior to Screening.
- Ability to perform acceptable and reproducible spirometry.
- Post-bronchodilator (four puffs of albuterol) spirometry at Screening demonstrating the following:
- FEV1/ FVC ratio of ≤0.70
- FEV1 ≥30% and ≤70% of predicted normal* *National Health and Nutrition Examination Survey (NHANES) III (Hankinson et al, 1999) will be used as the reference for normal predicted values.
- Clinically stable COPD in the 4 weeks prior to Screening (Visit 1) and during the period between Visits 1 and 2.
- A score of ≥2 on the modified Medical Research Council (mMRC) dyspnea scale at Screening.
- A chest X-ray (posterior-anterior) at Screening, or in the 12 months prior to Screening showing no clinically significant abnormalities unrelated to COPD.
- Meet the concomitant medication restrictions and be expected to do so for the rest of the study.
- Current and former smokers with smoking history of ≥10 pack years.
- Capable of withdrawing from long acting bronchodilators (other than tiotropium) for the duration of the study, and short acting bronchodilators for 6 hours prior to dosing.
Who cannot join
- A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to the first treatment.
- A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to the first treatment.
- Intolerance or hypersensitivity to albuterol, tiotropium or other muscarinic receptor antagonists.
- Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, uncontrolled or unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension or other active pulmonary diseases.
- Previous lung resection or lung reduction surgery.
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- Pulmonary rehabilitation, unless such treatment has been stable from 4 weeks prior to Screening and remains stable during the study.
- Oral therapies for COPD (e.g. oral steroids, theophylline, and roflumilast) or antibiotics within 3 months prior to Screening, or ICS therapy within 4 weeks prior to Screening
- Prior exposure to RPL554.
- History of, or reason to believe a patient has, drug or alcohol abuse within the past 5 years.
- Received an experimental drug within 30 days or five half-lives, whichever is longer.
- Women who are pregnant or breast-feeding.
- Patients with uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the Investigator believes are clinically significant. This includes any hepatic disease or moderate to severe renal impairment.
- Documented clinically significant cardiovascular disease such as: any history of arrhythmias, angina, recent (<1 year) or suspected myocardial infarction, congestive heart failure, unstable or uncontrolled hypertension, or diagnosis of hypertension within 3 months prior to Screening.
- Use of non-selective oral β-blockers.
- Major surgery (requiring general anesthesia) within 6 weeks prior to Screening, lack of full recovery from surgery at Screening, or planned surgery through the end of the study.
- Required use of oxygen therapy, even on an occasional basis.
- History of malignancy of any organ system within 5 years, with the exception of localized skin cancers (basal or squamous cell).
- Clinically significant abnormal values for laboratory safety tests (hematology, blood chemistry, viral serology or urinalysis) at Screening, as determined by the Investigator. In particular, alanine aminotransferase or aspartate aminotransferase cannot be more than twice the upper limit of normal.
- Patients with conditions which are sensitive to antimuscarinic effects such as narrow angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction.
- Current marijuana use (all forms).
- A disclosed history or one known to the Investigator, of significant non-compliance in previous investigational studies or with prescribed medications.
- Any other reason that the Investigator considers makes the patient unsuitable to participate.
Trial locations and contacts
50 sites in 1 country.
50 sites in 1 country
United States50 sites
Vitalink Research - Anderson
Anderson, South Carolina, 29621
Pinnacle Research Group, LLC
Anniston, Alabama, 36207
Meris Clinical Research
Brandon, Florida, 33511
Lowcountry Lung and Critical Care, PA
Charleston, South Carolina, 29406
American Health Research
Charlotte, North Carolina, 28078
New Horizons Clinical Research
Cincinnati, Ohio, 45242
Clinical Research of West Florida
Clearwater, Florida, 33765
VitaLink-Columbia
Columbia, South Carolina, 33765
Columbus Regional Research Institute
Columbus, Georgia, 31904
Aventiv Research, Inc
Columbus, Ohio, 43213
VitaLink Research - Hamilton Mill
Dacula, Georgia, 30019
Aventiv Research, Inc
Dublin, Ohio, 43016
VitaLink Research - Duluth
Duluth, Georgia, 30096
VitaLink Research - Easley
Easley, South Carolina, 29640
Genesis Clinical Research and Consulting, LLC
Fall River, Massachusetts, 02723
Pulmonary Research Institute of Southeast Michigan
Farmington Hills, Michigan, 48336
Piedmont Research Partners, LLC
Fort Mill, South Carolina, 29707
Cities Research Center
Fridley, Minnesota, 34741
California Research Medical Group, Inc
Fullerton, California, 92835
VitaLink Research-Gaffney
Gaffney, South Carolina, 29340
Clinical Research of Gastonia
Gastonia, North Carolina, 28054
VitaLink Research-Greenville
Greenville, South Carolina, 29615
VitaLink Research-UPSTATE
Greenville, South Carolina, 29615
Research Carolina of Huntersville
Huntersville, North Carolina, 28078
Pulmonary Disease Specialists, PA d/b/a PDS Research
Kissimmee, Florida, 34741
New Phase Research & Development
Knoxville, Tennessee, 37909
Innovative Clinical Research
Lafayette, Colorado, 80026
FMC Science, LLC
Lampasas, Texas, 76550
Gwinnett Biomedical Research
Lawrenceville, Georgia, 30046
Medical Research of Central Florida, LLC
Leesburg, Florida, 34748
DCOL Center for Clinical Research
Longview, Texas, 75605
Southern California Institute For Respiratory Diseases, Inc.
Los Angeles, California, 90048
Metroplex Pulmonary and Sleep Center
McKinney, Texas, 75069
Crisor, LLC
Medford, Oregon, 97504
Clinical Trials of Florida, LLC
Miami, Florida, 33186
Clinical Research of Lake Norman
Mooresville, North Carolina, 28117
Clinical Research of Charleston
Mt. Pleasant, South Carolina, 29464
Peninsula Research, Ormond Beach, LLC
Ormond Beach, Florida, 32174
Medsol Clinical Research Center, Inc
Port Charlotte, Florida, 33952
Progressive Medical Research
Port Orange, Florida, 32127
IACT Health
Rincon, Georgia, 31326
Clinical Research of Rock Hill
Rock Hill, South Carolina, 29732
Vitalink Research-Seneca
Seneca, South Carolina, 29678
Fusion Clinical Research of Spartanburg, LLC
Spartanburg, South Carolina, 29301
Spartanburg Medical Research
Spartanburg, South Carolina, 29301
Vitalink Research-Spartanburg
Spartanburg, South Carolina, 29303
Pasadena Center for Medical Research, LLC
St. Petersburg, Florida, 33707
VitaLink Research - Union
Union, South Carolina, 29379
Vitalink
Winder, Georgia, 30680
Florida Pulmonary Research Institute, LLC
Winter Park, Florida, 32789
About this study
Official title: A Phase II, Randomized, Double-Blind, Placebo Controlled Dose Ranging Study to Assess the Effect of RPL554 Added on to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease
The purpose of this study is to investigate the dose response of RPL554 in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE that are still symptomatic despite treatment with a stable background of tiotropium over 4 weeks of treatment. This study is intended to support optimal dose selection for a Phase III program evaluating RPL554 as an add-on treatment to standard of care therapy.
Read the detailed description
This is a Phase IIb, randomized, double-blind, placebo controlled, multiple dose, parallel group study to investigate the effects of 4 weeks of treatment with nebulized RPL554 (at different dose levels) compared to placebo in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE on a stable background therapy of open-label tiotropium. The study comprises seven visits: Pre-screening (Visit 0), Screening (Visit 1) and then a Treatment Period consisting of Randomization (Visit 2), and weekly visits for 4 weeks (Visit 3 to Visit 6).
- Conditions
- COPD
- Being tested
- Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropium, Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropium, Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropium, Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium, Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropiumDrug
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.375 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropiumDrug
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 0.75 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropiumDrug
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 1.5 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropiumDrug
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● RPL554 3.0 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropiumDrug
Patients will be randomized to receive one of the following treatment arms plus tiotropiuim:
● Placebo twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication.
| Study group | Role | What they receive |
|---|---|---|
| RPL554 0.375 mg twice daily | Experimental | RPL554 0.375 mg twice daily Receives: Drug: Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropium |
| RPL554 0.75 mg twice daily | Experimental | RPL554 0.75 mg twice daily Receives: Drug: Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropium |
| RPL554 1.5 mg twice daily | Experimental | RPL554 1.5 mg twice daily Receives: Drug: Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropium |
| RPL554 3.0 mg twice daily | Experimental | RPL554 3.0 mg twice daily Receives: Drug: Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium |
| Placebo twice daily | Placebo comparator | Placebo twice daily Receives: Drug: Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Least Square (LS) Mean Change From Baseline Forced Expiratory Volume in 1 Second (FEV1) to Peak FEV1 at Week 4
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and peak FEV1 was defined as the maximum value in the 3 hours after dosing. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.
Measured: Baseline and Week 4
Secondary outcomes (16)
LS Mean Change From Baseline FEV1 to Average Area Under the Curve Over 3 Hours (AUC0-3h) FEV1 on Day 1 and at Weeks 1 to 4
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and average AUC0-3h FEV1 was defined as area under the curve over 3 hours of the FEV1, divided by 3 hours. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, and 3 hours post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FEV1 to Average Area Under the Curve Over 12 Hours (AUC0-12h) FEV1 on Day 1 and at Week 4
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and average AUC0-12h FEV1 was defined as area under the curve over 12 hours of the FEV1, divided by 12 hours. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1 and at Week 4
LS Mean Change From Baseline FEV1 to Peak FEV1 on Day 1 and at Weeks 1 to 3
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and peak FEV1 was defined as the maximum value in the 3 hours after dosing. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes post-dose on Day 1 and Weeks 1, 2 and 3
LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 1 to 4
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and morning trough FEV1 was defined as the last pre-dose value. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1) and morning pre-dose on Weeks 1, 2, 3 and 4
LS Mean Change From Baseline to the Mean Weekly Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score at Weeks 1 to 4
The E-RS scale consists of 11 questions, with 3 sub-domains of: breathlessness, cough and sputum, and chest symptoms. The E-RS sub-domain score was calculated as the sum from the relevant questions. The E-RS:COPD scale has a scoring range of 0 to 40. Higher scores indicates severe respiratory symptoms. Baseline was the mean over the 7 days prior to first intake of study treatment. Scores were derived weekly as the mean over 7 days prior to the visit, using only days where data was recorded. The E-RS:COPD was measured by daily electronic diary (e-diary).
Measured: Baseline and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline in the St George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score at Weeks 2 and 4
Patients completed the SGRQ-C consisting of 40 items each weighted from 0 to a possible maximum of 100. Items 1-7 produced the symptoms score, 9-12 the activity score, and items 8, 10, 11, 13 and 14 the impacts score. Each component sub-score was calculated as a percentage of the summed weights of each item out of the sum of the maximum possible weight for that component (range 0-100). The total score was calculated by summing the weights to all positive responses in each component, where a positive item indicated the presence of symptoms, expressed as a percentage (range 0-100). Higher scores indicated a worse outcome. The SGRQ-C was measured at Week 2 and 4 visits.
Measured: Baseline, Weeks 2 and 4
LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 2 and 4
The TDI is a questionnaire that focussed on 3 sub-domains: functional impairment, magnitude of task and magnitude of effort. Sub-domain score was calculated as the sum from the related questions. Total score was calculated as the sum of the sub-domain scores. The TDI measures the change in dyspnea severity from the baseline as measured by the baseline dyspnea index. It was rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement). Higher scores indicate better outcome.
Measured: Weeks 2 and 4
LS Mean Patient Global Assessment of Change (PGAC) Questionnaire Total Score at Weeks 2 and 4
The PGAC is a single question assessment to determine whether patients noticed a change in their breathing since the start of the study. Patients were asked to respond to a PGAC question asking, "Compared with prior to the study start, how do you feel your breathing is?" on a scale of '1=much worse' to '5=much better', with '3=no change'. Higher scores indicate better outcome.
Measured: Weeks 2 and 4
LS Mean Change From Baseline to the Mean Weekly Values Over Weeks 1 to 4 in Number of Puffs of Rescue Medication
Use of rescue medication (albuterol) per visit was calculated as the LS mean use daily over total number of days between previous visit (inclusive) and the following visit. Baseline use was the mean over the last 7 days of the run-in phase (calculated as the sum of puffs taken, divided by number of days data has been recorded).
Measured: Baseline and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline Forced Vital Capacity (FVC) to Peak FVC on Day 1 and at Weeks 1 to 4
Forced spirometry maneuvers including the FVC were used to assess pulmonary function. Baseline FVC was defined as the value of FVC assessed 30 minutes before first administration and peak FVC was defined as the maximum value in the 3 hours after dosing. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FVC to Average AUC0-3h FVC on Day 1 and at Weeks 1 to 4
Forced spirometry maneuvers including the FVC were used to assess pulmonary function. Baseline FVC was defined as the value of FVC assessed 30 minutes before first administration and average AUC0-3h FVC was defined as area under the curve over 3 hours of the FVC, divided by 3 hours. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, and 3 hours post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FVC to Average AUC0-12h FVC on Day 1 and at Week 4
Forced spirometry maneuvers including the FVC were used to assess pulmonary function. Baseline FVC was defined as the value of FVC assessed 30 minutes before first administration and average AUC0-12h FVC was defined as area under the curve over 12 hours of the FVC, divided by 12 hours. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1 and at Week 4
LS Mean Change From Baseline FVC to Morning Trough FVC at Weeks 1 to 4
Forced spirometry maneuvers including the FVC were used to assess pulmonary function. Baseline FVC was defined as the value of FVC assessed 30 minutes before first administration and morning trough FVC was defined as the last pre-dose value. Spirometry assessments were performed in accordance with ATS/ERS guidelines.
Measured: Baseline (30 minutes before first administration on Day 1) and morning pre-dose on Weeks 1, 2, 3 and 4
Steady-State Plasma Concentrations of Tiotropium on Day 1 and at Week 2
Blood samples were taken to determine steady-state plasma concentrations of tiotropium prior to and following 14 days of treatment with RPL554.
Measured: Pre-dose on Day 1 and Week 2
Steady-State Plasma Concentrations of RPL554 at Week 2
Blood samples were taken to determine steady-state plasma concentrations of RPL554 following 14 days of treatment with RPL554.
Measured: Pre-dose at Week 2
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any undesirable experience occurring to a patient, or worsening in a patient, whether considered related to the study medication or not. All AEs which started after the first dose of study treatment or started prior to first dose of study treatment and worsened, based on the Investigator's assessment of severity, on or after first dose of study treatment were considered to be treatment-emergent. A serious adverse event is any adverse experience that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or other important medical events.
Measured: TEAEs were collected from the first dose of study treatment up to 1 week after the final study visit at Week 4, approximately 5 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2019
- Study start1 May 2019
- Primary completion15 Nov 2019
- Study completion15 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 416 participants (actual)
Sponsor and investigators
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd, LGC Limited
- Responsible party
- Sponsor
- Investigators
- Gary Ferguson, Principal investigator, Pulmonary Research Institute of Southeast Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03937479
- Sponsor's protocol ID
- RPL554-CO-205
- Status last verified
- Oct 2020
- First submitted
- 1 May 2019
- Last updated
- 20 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-Blind, Placebo Controlled Dose Ranging Study to Assess the Effect of RPL554 Added on to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease
- ClinicalTrials.gov ID
- NCT03937479
- Acronym / sponsor ID
- RPL554-CO-205
- Conditions
- COPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 416 participants (actual)
- Lead sponsor
- Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USAIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd, LGC Limited
- Study start
- 1 May 2019 (actual)
- Primary completion
- 15 Nov 2019 (actual)
- Study completion
- 15 Nov 2019 (actual)
- First posted
- 3 May 2019 (actual)
- Results
- Posted 28 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the dose response of RPL554 in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE that are still symptomatic despite treatment with a stable background of tiotropium over 4 weeks of treatment. This study is intended to support optimal dose selection for a Phase III program evaluating RPL554 as an add-on treatment to standard of care therapy.
Detailed description
This is a Phase IIb, randomized, double-blind, placebo controlled, multiple dose, parallel group study to investigate the effects of 4 weeks of treatment with nebulized RPL554 (at different dose levels) compared to placebo in patients with moderate to severe CHRONIC OBSTRUCTIVE PULMONARY DISEASE on a stable background therapy of open-label tiotropium. The study comprises seven visits: Pre-screening (Visit 0), Screening (Visit 1) and then a Treatment Period consisting of Randomization (Visit 2), and weekly visits for 4 weeks (Visit 3 to Visit 6).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| RPL554 0.375 mg twice daily | Experimental | Drug: Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropiumRPL554 0.375 mg twice daily |
| RPL554 0.75 mg twice daily | Experimental | Drug: Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropiumRPL554 0.75 mg twice daily |
| RPL554 1.5 mg twice daily | Experimental | Drug: Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropiumRPL554 1.5 mg twice daily |
| RPL554 3.0 mg twice daily | Experimental | Drug: Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropiumRPL554 3.0 mg twice daily |
| Placebo twice daily | Placebo comparator | Drug: Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropiumPlacebo twice daily |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Sign an informed consent document indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
- Male or female aged between 40 and 80 years inclusive, at the time of informed consent.
- Must agree to meet the following from the first dose up to 1 month after the last dose of study medication:
- Have a 12-lead ECG recording at Screening showing the following (and no changes in the pre-dose value at the first treatment deemed clinically significant by the Investigator):
- Capable of complying with study restrictions and procedures, including ability to use the nebulizer correctly.
Key exclusion criteria (23 listed)
- A history of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation.
- COPD exacerbation requiring oral or parenteral steroids, or lower respiratory tract infection requiring antibiotics, within 3 months of Screening or prior to the first treatment.
- A history of one or more hospitalizations for COPD or pneumonia within 6 months of Screening or prior to the first treatment.
- Intolerance or hypersensitivity to albuterol, tiotropium or other muscarinic receptor antagonists.
- Other respiratory disorders: Patients with a current diagnosis of asthma, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, uncontrolled or unstable sleep apnea, known alpha-1 antitrypsin deficiency, core pulmonale, clinically significant pulmonary hypertension or other active pulmonary diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropiumPatients will be randomized to receive one of the following treatment arms plus tiotropiuim: ● RPL554 0.375 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication. | Drug | RPL554 0.375 mg twice daily |
| Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropiumPatients will be randomized to receive one of the following treatment arms plus tiotropiuim: ● RPL554 0.75 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication. | Drug | RPL554 0.75 mg twice daily |
| Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropiumPatients will be randomized to receive one of the following treatment arms plus tiotropiuim: ● RPL554 1.5 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication. | Drug | RPL554 1.5 mg twice daily |
| Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropiumPatients will be randomized to receive one of the following treatment arms plus tiotropiuim: ● RPL554 3.0 mg twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication. | Drug | RPL554 3.0 mg twice daily |
| Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropiumPatients will be randomized to receive one of the following treatment arms plus tiotropiuim: ● Placebo twice daily The approximate planned duration for each completed patient will be 14 days of run-in and 28 days of treatment with study medication. | Drug | Placebo twice daily |
Primary outcome
Least Square (LS) Mean Change From Baseline Forced Expiratory Volume in 1 Second (FEV1) to Peak FEV1 at Week 4
Time frame: Baseline and Week 4
Forced spirometry maneuvers including the FEV1 were used to assess pulmonary function. Baseline FEV1 was defined as the value of FEV1 assessed 30 minutes before first administration and peak FEV1 was defined as the maximum value in the 3 hours after dosing. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.
16 secondary outcomes
LS Mean Change From Baseline FEV1 to Average Area Under the Curve Over 3 Hours (AUC0-3h) FEV1 on Day 1 and at Weeks 1 to 4
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, and 3 hours post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FEV1 to Average Area Under the Curve Over 12 Hours (AUC0-12h) FEV1 on Day 1 and at Week 4
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1 and at Week 4
LS Mean Change From Baseline FEV1 to Peak FEV1 on Day 1 and at Weeks 1 to 3
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes post-dose on Day 1 and Weeks 1, 2 and 3
LS Mean Change From Baseline FEV1 to Morning Trough FEV1 at Weeks 1 to 4
Time frame: Baseline (30 minutes before first administration on Day 1) and morning pre-dose on Weeks 1, 2, 3 and 4
LS Mean Change From Baseline to the Mean Weekly Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score at Weeks 1 to 4
Time frame: Baseline and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline in the St George's Respiratory Questionnaire - COPD Specific (SGRQ-C) Total Score at Weeks 2 and 4
Time frame: Baseline, Weeks 2 and 4
LS Mean Transition Dyspnea Index (TDI) Questionnaire Total Score at Weeks 2 and 4
Time frame: Weeks 2 and 4
LS Mean Patient Global Assessment of Change (PGAC) Questionnaire Total Score at Weeks 2 and 4
Time frame: Weeks 2 and 4
LS Mean Change From Baseline to the Mean Weekly Values Over Weeks 1 to 4 in Number of Puffs of Rescue Medication
Time frame: Baseline and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline Forced Vital Capacity (FVC) to Peak FVC on Day 1 and at Weeks 1 to 4
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FVC to Average AUC0-3h FVC on Day 1 and at Weeks 1 to 4
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, and 3 hours post-dose on Day 1 and Weeks 1, 2, 3 and 4
LS Mean Change From Baseline FVC to Average AUC0-12h FVC on Day 1 and at Week 4
Time frame: Baseline (30 minutes before first administration on Day 1); 30 minutes and 1, 2, 3, 4, 6, 8 and 12 hours post-dose on Day 1 and at Week 4
LS Mean Change From Baseline FVC to Morning Trough FVC at Weeks 1 to 4
Time frame: Baseline (30 minutes before first administration on Day 1) and morning pre-dose on Weeks 1, 2, 3 and 4
Steady-State Plasma Concentrations of Tiotropium on Day 1 and at Week 2
Time frame: Pre-dose on Day 1 and Week 2
Steady-State Plasma Concentrations of RPL554 at Week 2
Time frame: Pre-dose at Week 2
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Time frame: TEAEs were collected from the first dose of study treatment up to 1 week after the final study visit at Week 4, approximately 5 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Ferguson principal investigator
Pulmonary Research Institute of Southeast Michigan
50 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of COPD, run by Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA at 50 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Least Square (LS) Mean Change From Baseline Forced Expiratory Volume in 1 Second (FEV1) to Peak FEV1 at Week 4 (time frame: Baseline and Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2020.