Phase 3 Multinational, Randomized, Double-blind, Placebo-controlled Study on Inhaled Treprostinil Efficacy and Safety in Idiopathic Pulmonary Fibrosis
- Trial ID
- 2024-514761-19-00
- Protocol
- RIN-PF-303
- Sponsor
- United Therapeutics Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 study is to evaluate the **superiority** of inhaled **treprostinil** compared to placebo in subjects with **Idiopathic Pulmonary Fibrosis** (IPF). The primary endpoint is the change in absolute Forced Vital Capacity (FVC) from baseline to Week 52. This measure is clinically relevant as FVC is a critical indicator of lung function and disease progression in IPF patients. The study aims to determine whether inhaled treprostinil can significantly improve or stabilize lung function over a one-year period compared to placebo, potentially offering a new therapeutic option for managing this progressive and debilitating condition.
Participants
The clinical trial involves a total of **433 participants** diagnosed with **Idiopathic Pulmonary Fibrosis** (IPF). The study population includes both male and female subjects, aged 40 years and older, who have been confirmed to have IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline. Participants were selected based on specific criteria, including a forced vital capacity (FVC) of at least 45% predicted at screening. The trial includes individuals who are on a stable and optimized dose of either pirfenidone or nintedanib for at least 30 days prior to baseline, but not both. Lifestyle considerations such as the use of contraception for women of childbearing potential and condom use for males with partners of childbearing potential are required. The trial population is considered vulnerable, and participants must be able to communicate effectively with study personnel and comply with protocol requirements. The selection process ensures that participants are reliable and likely to adhere to study protocols, including attending all study visits.
Plans and Procedures
The clinical trial is a **randomized, double-blind, placebo-controlled** study designed to evaluate the efficacy and safety of inhaled **treprostinil** in subjects with **Idiopathic Pulmonary Fibrosis** (IPF). The trial is a Phase 3 study with an estimated duration from October 2022 to July 2025. Participants will be randomly assigned to receive either the active treatment, treprostinil nebuliser solution, or a placebo solution identical in appearance but lacking the active drug substance. The primary objective is to assess the change in absolute forced vital capacity (FVC) from baseline to Week 52, with secondary endpoints including time to clinical worsening, time to first acute exacerbation of IPF, overall survival at Week 52, and changes in various health-related quality of life measures.
The trial will commence with a screening visit to confirm eligibility based on inclusion criteria such as age, diagnosis of IPF, and lung function parameters. Participants will then undergo a baseline visit where initial assessments and randomization occur. Follow-up visits will be scheduled at regular intervals to monitor safety, efficacy, and adherence to the study protocol. These visits will include assessments of lung function, symptom questionnaires, and safety evaluations. The end-of-study visit will occur at Week 52, marking the conclusion of the participant's involvement in the trial.
Participant involvement is expected to last approximately 52 weeks, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with study procedures. The study is designed to ensure rigorous monitoring and data collection to support the evaluation of treprostinil's therapeutic potential in IPF, with the ultimate goal of improving patient outcomes in this challenging condition.
Treatment
The clinical trial involves the administration of **Treprostinil**, an experimental medication, in the form of a nebuliser solution. Treprostinil is a chemical substance provided by United Therapeutics Corporation. The pharmaceutical form is a nebuliser solution, and it is administered via inhalation using an ultrasonic nebuliser. The maximum daily dose is 360 micrograms, with a total maximum dose of 393,120 micrograms over a treatment period of 52 weeks. The administration device, the TD-300/A (TD-300) nebuliser, is part of the Tyvaso Inhalation System, which includes two nebulisers, accessories, and an initial month of supplies. The inhalation route ensures direct delivery to the lungs, which is critical for the treatment of **Idiopathic Pulmonary Fibrosis**.
The study also includes a **placebo** treatment, which is a nebuliser solution identical in appearance and administration to the Treprostinil solution but lacks the active drug substance. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators know which treatment is being administered. This placebo control is essential for evaluating the efficacy and safety of inhaled Treprostinil by comparing it against a non-active treatment. The placebo is administered with the same frequency and via the same inhalation route as the active drug, ensuring consistency in the study protocol.
Efficacy
The efficacy of inhaled **treprostinil** in subjects with Idiopathic Pulmonary Fibrosis (IPF) will be assessed through a randomized, double-blind, placebo-controlled, multinational Phase 3 study. The primary endpoint for evaluating efficacy is the change in absolute Forced Vital Capacity (FVC) from baseline to Week 52. This measurement will be used to determine the superiority of inhaled treprostinil compared to placebo.
Secondary endpoints include several parameters: time to clinical worsening, which encompasses time to death, respiratory hospitalization, or a ≥10% relative decline in % predicted FVC; time to first acute exacerbation of IPF; overall survival at Week 52; change from baseline in % predicted FVC at Week 52; change from baseline in King's Brief Interstitial Lung Disease Questionnaire score at Week 52; and change from baseline in diffusion capacity of lungs for carbon monoxide at Week 52. These endpoints will provide a comprehensive assessment of the treatment's impact on disease progression and patient quality of life.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject gives voluntary informed consent to participate in the study. 2. Subject is ≥40 years of age, inclusive, at the time of signing informed consent. 3. The subject has a diagnosis of IPF based on the 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline (Raghu 2018) and confirmed by central review of HRCT (performed within the previous 12 months) and if available, surgical lung biopsy. HRCT imaging must be ""consistent with UIP,"" defined as meeting either criteria A, B, and C; or criteria A and C; or criteria B and C below: a. Subpleural and basal predominant honeycombing b. Subpleural and basal predominant reticular pattern with peripheral traction bronchiectasis or traction bronchiolectasis c. Absence of atypical features (eg, predominant ground-glass opacity, nodules, consolidation, etc). If ground-glass opacity is present, it must be less than the accompanying reticular pattern. Subjects with HRCT features deemed indeterminate for IPF (subpleural and basal predominant, subtle, reticulating pattern of fibrosis) may be considered for inclusion if coupled with a histopathological pattern of ""UIP"" or ""probable UIP"" on surgical lung biopsy and confirmed by central review. 4. FVC ≥45% predicted at Screening. 5. Subjects on pirfenidone or nintedanib must be on a stable and optimized dose for ≥30 days prior to Baseline. Concomitant use of both pirfenidone and nintedanib is not permitted. 6. Women of childbearing potential must be non-pregnant (as confirmed by a urine pregnancy test at Screening and Baseline) and non-lactating, and will do 1 of the following: a. Abstain from intercourse (when it is in line with their preferred and usual lifestyle) b. Use 2 medically acceptable, highly effective forms of contraception for the duration of the study, and at least 30 days after discontinuing study drug. 1. Medically acceptable, highly effective forms of contraception can include approved hormonal contraceptives (oral, injectable, and implantable) and barrier methods (such as a condom or diaphragm) when used with a spermicide.Women who are successfully sterilized (including hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or postmenopausal (defined asamenorrhea for at least 12 consecutive months) are not considered to be of reproductive potential. 7. Males with a partner of childbearing potential must use a condom for the duration of treatment and for at least 48 hours after discontinuing study drug. 8. In the opinion of the Investigator, the subject is able to 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
- Subject is pregnant or lactating 2. Subject has primary obstructive airway physiology: FEV1/FVC <0.70 at Screening. 3. The subject has shown intolerance or significant lack of efficacy to a prostacyclin or prostacyclin analogue that resulted in discontinuation or inability to effectively titrate that therapy. 4. The subject has received any PAH-approved therapy, including prostacyclin therapy (epoprostenol, treprostinil, iloprost, or beraprost; except for acute vasoreactivity testing), IP receptor agonists (selexipag), endothelin receptor antagonists, phosphodiesterase type 5 inhibitors (PDE5-Is), or soluble guanylate cyclase stimulators within 60 days prior to Baseline. As needed use of a PDE5-I for erectile dysfunction is permitted, provided no doses are taken within 48 hours of any studyrelated efficacy assessments. 5. Use of any of the following medications: a. Azathioprine (AZA), cyclosporine, mycophenolate mofetil, tacrolimus, oral corticosteroids (OCS) >20 mg/day or the combination of OCS+AZA+N-acetylcysteine within 30 days prior to Baseline. b. Cyclophosphamide within 60 days prior to Baseline c. Rituximab within 6 months prior to Baseline 6. The subject is receiving >10 L/min of oxygen supplementation by any mode of delivery at rest at Baseline. 7. Exacerbation of IPF or active pulmonary or upper respiratory infection within 30 days prior to Baseline. Subjects must have completed any antibiotic or steroid regimens for treatment of the infection or acute exacerbation more than 30 days prior to Baseline to be eligible. If hospitalized for an acute exacerbation of IPF or a pulmonary or upper respiratory infection, subjects must have been discharged more than 90 days prior to Baseline to be eligible. 8. Uncontrolled cardiac disease, defined as myocardial infarction within 6 months prior to Baseline or unstable angina within 30 days prior to Baseline. 9. In the opinion of the Investigator, the subject has any condition that would interfere with the interpretation of study assessments or would impair study participation or cooperation. 10. Use of any other investigational drug/device or participation in any investigational study in which the subject received a medical intervention (ie, procedure, device, medication/supplement) within 30 days prior to Screening. Subjects participating in non-interventional, observational, or registry studies are eligible. 11. Life expectancy <6 months due to IPF or a concomitant illness. 12. Acute pulmonary embolism within 90 days prior to Baseline "
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 04 Oct 2022 | 68 |
 Denmark | Not Recruiting | 04 Oct 2022 | 31 |
 France | Not Recruiting | 04 Oct 2022 | 94 |
 Germany | Not Recruiting | 04 Oct 2022 | 38 |
 Italy | Not Recruiting | 04 Oct 2022 | 60 |
 The Netherlands | Not Recruiting | 04 Oct 2022 | — |
 Spain | Not Recruiting | 04 Oct 2022 | 83 |
| Netherlands | — | — | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
The Placebo Nebuliser Solution is a solution dosage form for nebulisation identical to
Treprostinil Nebuliser Solution drug product except for the absence of the treprostinil drug
substance. | Placebo | N/A | — | — | — | N/A |
Treprostinil | Test | NEBULISER SOLUTION | INHALATION USE | 360 | 52 | PRD9910879 |