A Phase 3 Adaptive Study to Evaluate the Safety and Efficacy of Inhaled Treprostinil in Patients With PH Due to COPD
This is a multicenter, randomized, double-blind, placebo-controlled, 30-week, adaptive cross-over study, with a Treatment Period of approximately 26 weeks under the Original Design or, if applicable, a 17-week parallel study, with a Treatment Period of approximately 14 weeks under the Contingent Design.
- Pulmonary Hypertension
- Chronic Obstructive Pulmonary Disease
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
Participants who meet the following criteria may be included in the study:
1. Subject 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. Subject 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 (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 2019) 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 subject has a resting saturation peripheral capillary oxygenation (SpO2) greater than or equal to 90%, with or without supplemental oxygen, but not to exceed 10 L/min oxygen supplementation by any mode of delivery at rest 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. 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 mmHg
3. A 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 60 days prior to start of Screening Visit 1 and remain on the same dose throughout the Screening Period.
9. Participants on medications for conditions unrelated to COPD must be on a stable and optimized dose for greater than or equal to 30 days prior to start of Screening Visit 1 and should remain on the same dose until the end of the study. Exceptions are anticoagulants and diuretics.
10. In the opinion of the Investigator, the subject can communicate effectively with study personnel and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.
The following will exclude participants from the study:
1. The subject 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 CT imaging during Screening Visit 1, the subject 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 subject has received any Food and Drug Administration (FDA)-approved medication for the treatment of PAH (ie, prostacyclin, prostacyclin receptor agonist, endothelin receptor antagonist [ERA], phosphodiesterase type 5 inhibitor [PDE5-I], or soluble guanylate cyclase [sGC] stimulator) within 60 days of start of Screening Visit 1, except if received for acute vasoreactivity testing.
4. The subject has previously been diagnosed with alpha-1 antitrypsin deficiency.
5. The subject has had any prior intolerance to 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. The subject 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.
8. The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest.
9. Currently using any inhaled tobacco products, electronic cigarettes, or inhaled substances, excluding prescribed respiratory therapies, unless approved by the Medical Monitor.
10. Significant history of substance abuse within 6 months prior to start of Screening Visit 1.
11. 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. For the purpose of this protocol, treatment of sequalae of COPD are considered COPD exacerbation.
12. 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.
13. The subject has an uncontrolled medical condition deemed by an Investigator to pose an undue risk to the subject.
14. The subject has any form of congenital heart disease (repaired or unrepaired; other than a patent foramen ovale).
15. The subject has a Body Mass Index greater than or equal to 45 kg/m2 during Screening Visit 1.
16. The subject has any musculoskeletal disorder (ie, arthritis of the lower limbs which limits ambulation, recent hip or knee joint replacement, artificial leg) or has any other condition that would likely be the primary limitation to ambulation.
17. Use of any investigational drug/device or participation in any investigational study with therapeutic intent within 30 days prior to start of Screening Visit 1.
18. 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.
- Phase 3
- Study Type
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Inhaled treprostinil delivered via an ultrasonic nebulizer with a target dosing regimen of 12 breaths (72 mcg) 4 times daily (QID)||
|Placebo delivered via an ultrasonic nebulizer for QID administration||
- United Therapeutics
Study ContactPrakash Sista, Ph.D.