Study Investigating the Effect of 4 Doses of RPL554 Given in Addition to Tiotropium to Patients With COPD

NCT03937479 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RPL554-CO-205
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 50

Brief 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. 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.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  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

  Baseline and Weeks 1, 2, 3 and 4

Study Arms (5)

RPL554 0.375 mg twice daily

EXPERIMENTAL

RPL554 0.375 mg twice daily

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

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

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

Drug: Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium

Placebo twice daily

PLACEBO COMPARATOR

Placebo twice daily

Drug: Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium

Interventions

Ensifentrine (formerly RPL554) 0.375 mg twice daily plus placebo, in addition to tiotropium DRUG

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.

RPL554 0.375 mg twice daily

Ensifentrine (formerly RPL554) 0.75 mg twice daily plus placebo, in addition to tiotropium DRUG

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.

RPL554 0.75 mg twice daily

Ensifentrine (formerly RPL554) 1.5 mg twice daily plus placebo, in addition to tiotropium DRUG

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.

RPL554 1.5 mg twice daily

Ensifentrine (formerly RPL554) 3.0 mg twice daily plus placebo, in addition to tiotropium DRUG

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.

RPL554 3.0 mg twice daily

Ensifentrine (formerly RPL554) placebo twice daily, in addition to tiotropium DRUG

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.

Placebo twice daily

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Verona Pharma plc: lead
• Iqvia Pty Ltd: collaborator
• LGC Limited: collaborator

Study Sites (50)

Pinnacle Research Group, LLC

Anniston, Alabama, 36207, United States

Location

California Research Medical Group, Inc

Fullerton, California, 92835, United States

Location

Southern California Institute For Respiratory Diseases, Inc.

Los Angeles, California, 90048, United States

Location

Innovative Clinical Research

Lafayette, Colorado, 80026, United States

Location

Meris Clinical Research

Brandon, Florida, 33511, United States

Location

Clinical Research of West Florida

Clearwater, Florida, 33765, United States

Location

Pulmonary Disease Specialists, PA d/b/a PDS Research

Kissimmee, Florida, 34741, United States

Location

Medical Research of Central Florida, LLC

Leesburg, Florida, 34748, United States

Location

Clinical Trials of Florida, LLC

Miami, Florida, 33186, United States

Location

Peninsula Research, Ormond Beach, LLC

Ormond Beach, Florida, 32174, United States

Location

Medsol Clinical Research Center, Inc

Port Charlotte, Florida, 33952, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Pasadena Center for Medical Research, LLC

St. Petersburg, Florida, 33707, United States

Location

Florida Pulmonary Research Institute, LLC

Winter Park, Florida, 32789, United States

Location

Columbus Regional Research Institute

Columbus, Georgia, 31904, United States

Location

VitaLink Research - Hamilton Mill

Dacula, Georgia, 30019, United States

Location

VitaLink Research - Duluth

Duluth, Georgia, 30096, United States

Location

Gwinnett Biomedical Research

Lawrenceville, Georgia, 30046, United States

Location

IACT Health

Rincon, Georgia, 31326, United States

Location

Vitalink

Winder, Georgia, 30680, United States

Location

Genesis Clinical Research and Consulting, LLC

Fall River, Massachusetts, 02723, United States

Location

Pulmonary Research Institute of Southeast Michigan

Farmington Hills, Michigan, 48336, United States

Location

Cities Research Center

Fridley, Minnesota, 34741, United States

Location

American Health Research

Charlotte, North Carolina, 28078, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

Research Carolina of Huntersville

Huntersville, North Carolina, 28078, United States

Location

Clinical Research of Lake Norman

Mooresville, North Carolina, 28117, United States

Location

New Horizons Clinical Research

Cincinnati, Ohio, 45242, United States

Location

Aventiv Research, Inc

Columbus, Ohio, 43213, United States

Location

Aventiv Research, Inc

Dublin, Ohio, 43016, United States

Location

Crisor, LLC

Medford, Oregon, 97504, United States

Location

Vitalink Research - Anderson

Anderson, South Carolina, 29621, United States

Location

Lowcountry Lung and Critical Care, PA

Charleston, South Carolina, 29406, United States

Location

VitaLink-Columbia

Columbia, South Carolina, 33765, United States

Location

VitaLink Research - Easley

Easley, South Carolina, 29640, United States

Location

Piedmont Research Partners, LLC

Fort Mill, South Carolina, 29707, United States

Location

VitaLink Research-Gaffney

Gaffney, South Carolina, 29340, United States

Location

VitaLink Research-Greenville

Greenville, South Carolina, 29615, United States

Location

VitaLink Research-UPSTATE

Greenville, South Carolina, 29615, United States

Location

Clinical Research of Charleston

Mt. Pleasant, South Carolina, 29464, United States

Location

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

Vitalink Research-Seneca

Seneca, South Carolina, 29678, United States

Location

Fusion Clinical Research of Spartanburg, LLC

Spartanburg, South Carolina, 29301, United States

Location

Spartanburg Medical Research

Spartanburg, South Carolina, 29301, United States

Location

Vitalink Research-Spartanburg

Spartanburg, South Carolina, 29303, United States

Location

VitaLink Research - Union

Union, South Carolina, 29379, United States

Location

New Phase Research & Development

Knoxville, Tennessee, 37909, United States

Location

FMC Science, LLC

Lampasas, Texas, 76550, United States

Location

DCOL Center for Clinical Research

Longview, Texas, 75605, United States

Location

Metroplex Pulmonary and Sleep Center

McKinney, Texas, 75069, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

One patient who was randomized to RPL554 0.375 mg group was dispensed wrong treatment kit and received RPL554 3 mg. Patients were classified according to randomized treatment for the FAS and actual treatment received for safety and PK analysis sets.

Results Point of Contact

• Title: Nancy Herje
• Organization: Verona Pharma Plc

nancy.herje@veronapharma.com

+1 646-951-0961

Study Officials

• Gary Ferguson

  Pulmonary Research Institute of Southeast Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 3, 2019
• Study Start: May 1, 2019
• Primary Completion: November 15, 2019
• Study Completion: November 15, 2019
• Last Updated: November 20, 2020
• Results First Posted: October 28, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (50)