A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Participants With Pulmonary Hypertension (PH) Due to Chronic Obstructive Pulmonary Disease (COPD)

NCT ID: NCT03496623

Last Updated: 2023-11-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-08
• Study Completion Date: 2022-10-13

Brief Summary

The primary objective of this study is to demonstrate the efficacy of inhaled treprostinil compared to placebo in improving exercise ability as measured by change from baseline in 6-Minute Walk Distance (6MWD) following 12 weeks of active treatment in participants with PH-COPD.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, 34-week, cross-over study, with a Treatment Period of approximately 26 weeks under the Original Crossover Design or, if applicable, a 21-week parallel study, with a Treatment Period of approximately 14 weeks under the Contingent Parallel Design.

Conditions

Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Inhaled Treprostinil

Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 micrograms \[mcg\]) 4 times daily (QID)

Group Type: EXPERIMENTAL

Inhaled treprostinil solution

Intervention Type: DRUG

Treprostinil inhalation solution

Placebo

Placebo delivered via an ultrasonic nebulizer for QID administration

Group Type: PLACEBO_COMPARATOR

Placebo solution

Intervention Type: DRUG

Placebo solution

Interventions

Inhaled treprostinil solution

Treprostinil inhalation solution

Intervention Type: DRUG

Placebo solution

Placebo solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Participants who meet the following criteria may be included in the study:

1. Participant voluntarily gives informed consent to participate in the study.

2. Males and females 18 years of age and above at the time of informed consent.

1. Women of childbearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must agree to practice abstinence or use 2 highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, [<1% per year], such as approved hormonal contraceptives, barrier methods [such as condom or diaphragm] used with a spermicide, or an intrauterine device) for the duration of study treatment and for 48 hours after discontinuing study drug. Participants must have a negative pregnancy test at the Screening Visit 1 (urine [prior to the first dose of study medication] and serum) and Baseline Visit (Study Week 1) (urine).

2. Males with a partner of childbearing potential must agree to use a barrier method (condom) with a spermicide for the duration of treatment and for at least 48 hours after discontinuing study drug.

3. Diagnosis of PH-COPD (World Heath Organization [WHO] Group 3).

4. Clinical diagnosis of COPD will be made using the Global Initiative for Chronic

Obstructive Lung Disease (GOLD) diagnostic criteria (GOLD Criteria 2020) and spirometry with the following documented parameters measured during Screening Visit 1 (prior to start of low-dose inhaled treprostinil):

1. Forced expiratory volume in 1 second (FEV1) <80% predicted

2. FEV1/Forced vital capacity (FVC) <70

5. The participant has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 liters (L)/min oxygen supplementation by any mode of delivery during Screening Visit 1.

6. During Screening Visit 1 prior to start of low-dose inhaled treprostinil, a 6MWD greater than or equal to 100 meters.

7. Have a right heart catheterization (RHC) performed during Screening Visit 1. (A previous RHC obtained within 12 months prior to the start of Screening Visit 1 is acceptable for determining eligibility, even if done without oxygen or vasodilator challenge, and a repeat RHC is not required.) The following parameters must be documented for eligibility:

1. Pulmonary vascular resistance (PVR) greater than or equal to 4 Wood units

2. A pulmonary artery wedge pressure (PAWP) or left ventricular end-diastolic pressure (LVEDP) of less than or equal to 15 millimeters of mercury (mmHg)

3. A Pulmonary artery pressure mean (PAPm) of greater than or equal to 30 mmHg

8. Participants must be on a stable and optimized dose of chronic COPD medications for greater than or equal to 30 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period.

9. In the opinion of the Investigator, the participant can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

Exclusion Criteria

The following will exclude participants from the study:

1. The participant has a diagnosis of either pulmonary arterial hypertension (PAH) or pulmonary hypertension (PH) due to reasons other than COPD. This would include, but is not limited to, chronic thromboembolic PH or acute/recent deep vein thrombosis or pulmonary embolism, untreated or inadequately treated obstructive sleep apnea, connective tissue disease (including but not limited to systemic sclerosis/scleroderma or systemic lupus erythematosus), sarcoidosis, human immunodeficiency virus-1 infection, and other conditions under WHO Group 1, 2, 4, and 5 classifications.

2. Based on chest computed tomography (CT) imaging during Screening Visit 1, the participant has a confirmed diagnosis of WHO Group 3 PH, other than COPD, such as idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, diffuse parenchymal lung disease or interstitial lung disease. A previous chest CT scan performed within the 6 months prior to the start of Screening Visit 1 is also acceptable, and a repeat assessment is not required.

A redacted CT scan report (from Screening Visit 1 or dated within prior 6 months) should be provided to the Medical Monitor with the Pre-Baseline Review Form to confirm eligibility.

3. The participant has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (that is, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) at Screening Visit 1 and thereafter, except if received for acute vasoreactivity testing.

4. The participant has a previous diagnosis of homozygous alpha-1 antitrypsin deficiency.

5. The participant has any prior intolerance to inhaled prostanoid therapy.

6. Inability to tolerate low-dose (3 breaths, 18 mcg) study drug and/or inability to follow dosing regimen during the Screening Period (pre-randomization).

7. Unwilling or unable to use Sponsor-provided devices (actigraph, spirometer, or smart device).

8. The participant has evidence of clinically significant left-sided heart disease (including but not limited to left ventricular ejection fraction <40%, left ventricular hypertrophy,) or clinically significant cardiologic conditions, such as congestive heart failure, coronary artery disease, or valvular heart disease. Note: Participants with abnormal left ventricular function attributable to the effects of right ventricular overload will not be excluded, but a discussion with and approval by the Sponsor Medical Monitor is needed.

9. Any exacerbation of COPD (including hospitalization or outpatient therapy) or active pulmonary or upper respiratory infection 60 days prior to start of Screening Visit 1 through the Baseline Visit. This is defined as worsening of respiratory symptoms that required treatment with corticosteroids and/or antibiotics.

10. Initiation of pulmonary rehabilitation within 12 weeks prior to start of Screening Visit 1 or, in the opinion of the Investigator, pulmonary rehabilitation is likely to be needed during the study Treatment Period.

11. The participant has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).

12. The participant has any musculoskeletal disorder (severe arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or any other condition that would likely be the primary limitation to ambulation.

13. Use of any other investigational drug or device within 30 days prior to the start of Screening Visit 1.

14. Any other clinically significant illness or abnormal laboratory value(s) measured during the Screening Period that, in the opinion of the Investigator, might adversely affect the interpretation of the study data or safety of the participant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

United Therapeutics

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner University Medical Center

Phoenix, Arizona, United States

University of Arizona Clinical and Translational Science (CATS) Research Center

Tucson, Arizona, United States

Loma Linda University Medical Center

Loma Linda, California, United States

University of Southern California

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

West Los Angeles VA Healthcare Center

Los Angeles, California, United States

University of California Davis Medical Center

Sacramento, California, United States

Santa Barbara Pulmonary Associates

Santa Barbara, California, United States

University of Colorado Health Sciences Center

Aurora, Colorado, United States

South Denver Cardiology

Littleton, Colorado, United States

Hartford Hospital

Hartford, Connecticut, United States

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

St. Francis Medical Institute

Clearwater, Florida, United States

University of Florida Clinical Research Center

Gainesville, Florida, United States

St. Vincent's Lung, Sleep, and Critical Care Specialists

Jacksonville, Florida, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

Pulmonary Disease Specialists

Kissimmee, Florida, United States

University of Miami Hospital

Miami, Florida, United States

University of South Florida

Tampa, Florida, United States

Pulmonary & Critical Care of Atlanta

Atlanta, Georgia, United States

Georgia Clinical Research

Austell, Georgia, United States

University of Illinois Medical Center

Chicago, Illinois, United States

Advocate Aurora Health Care

Elmhurst, Illinois, United States

Advocate Condell Medical Center

Libertyville, Illinois, United States

Advocate Heart Institute & Pulmonology

Normal, Illinois, United States

Edward Heart Hospital

Oakbrook Terrace, Illinois, United States

Indiana University Healh North Hospital

Indianapolis, Indiana, United States

St. Vincent Medical Group, Inc.

Indianapolis, Indiana, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

University of Louisville Research Foundation

Louisville, Kentucky, United States

University of Maryland Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Detroit Medical Center Lung Institute

Detroit, Michigan, United States

Henry Ford Health System

Detroit, Michigan, United States

Spectrum Health

Grand Rapids, Michigan, United States

Beaumont Health

Troy, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

The University of New Mexico

Albuquerque, New Mexico, United States

Albany Medical College

Albany, New York, United States

The Mount Sinai Hospital

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

The Carl and Edyth Lindner Research Center at the Christ Hospital

Cincinnati, Ohio, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Clinical Research Associates of Central PA, LLC

DuBois, Pennsylvania, United States

Temple Lung Center

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center - Montefiore

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Statcare Pulmonary Consultants

Knoxville, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Texas Tech

El Paso, Texas, United States

Clear Lake Specialties/Tranquility Research

Webster, Texas, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Pulmonary Associates of Richmond, Inc.

Richmond, Virginia, United States

Carilion Clinic

Roanoke, Virginia, United States

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Hospital Britanico de Buenos Aires

Buenos Aires, , Argentina

El Cruce Hospital

Buenos Aires, , Argentina

Fundacion Favaloro

Ciudad Autonoma Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Ciudad Autonoma Buenos Aires, , Argentina

Hospital Italiano de Cordoba

Córdoba, , Argentina

Centro Medico 21 de Diciembre

Santa Fe, , Argentina

Lady Davis Carmel Medical Centre

Haifa, , Israel

Hadassah-Hebrew University Hospital

Jerusalem, , Israel

Rabin Medical Center

Petah Tiva, , Israel

The Chaim Sheba Medical Center

Tel Litwinsky, , Israel

CardioPulmonary Research Center

Guaynabo, , Puerto Rico

Countries

United States; Argentina; Israel; Puerto Rico

References

Nathan SD, Argula R, Trivieri MG, Aziz S, Gay E, Medarov B, Parambil J, Raina A, Risbano MG, Thenappan T, Soto JS, Bell H, Lacasse V, Sista P, Di Marino M, Smart A, Hawkes B, Nelson E, Bull T, Tapson V, Waxman A. Inhaled treprostinil in pulmonary hypertension associated with COPD: PERFECT study results. Eur Respir J. 2024 Jun 6;63(6):2400172. doi: 10.1183/13993003.00172-2024. Print 2024 Jun.

Reference Type: DERIVED

PMID: 38811045 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RIN-PH-304

Identifier Type: -

Identifier Source: org_study_id