A Randomized, Double-blind, Placebo-controlled, Multinational, Phase 3 Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects with Idiopathic Pulmonary Fibrosis (TETON-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

United Therapeutics Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

25 Jan 2023 → 30 Jun 2025

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

UNITED THERAPEUTICS CORPORATION

External identifiers

EU CT number

2024-514761-19-00

EudraCT number

2021-005881-17

ClinicalTrials.gov

NCT05255991

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

"The primary objective of RIN-PF-303 is to evaluate the superiority of inhaled treprostinil against
placebo for the change in absolute FVC from baseline to Week 52."

Conditions and MedDRA coding

Idiopathic Pulmonary Fibrosis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 1

1. 1. 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 "

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study is the change in absolute FVC in subjects with IPF from baseline to Week 52.

Secondary endpoints 1

1. • Time to clinical worsening (including time to death, respiratory hospitalization, or ≥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 •Change from baseline in diffusion capacity of lungs for carbon monoxide at Week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

United Therapeutics Corp.

Sponsor organisation

United Therapeutics Corp.

Address

55 Tw Alexander Drive, P. O. Box 14186 P. O. Box 14186

City

Durham

Postcode

27709-0152

Country

United States

Scientific contact point

Organisation

United Therapeutics Corp.

Contact name

Peter Smith

Public contact point

Organisation

United Therapeutics Corp.

Contact name

Regulatory Department

Third parties 9

Locations

7 EU/EEA countries · 46 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications