A study to evaluate the effects of Treprostinil Palmitil Inhalation Powder in participants with Pulmonary Hypertension with Interstitial Lung Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Insmed Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

24 Apr 2023 → 1 Apr 2026

Decision date (initial)

2024-04-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Insmed Incorporated

External identifiers

EU CT number

2023-505540-19-00

EudraCT number

2022-001950-45

ClinicalTrials.gov

NCT05649722

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Efficacy, Others

To evaluate the safety and tolerability of the long-term use of TPIP in participants with PH-ILD from Study INS1009-211 and other lead-in studies of TPIP in participants with PH-ILD (pulmonary hypertension associated with interstitial lung disease).

Secondary objectives 1

1. To evaluate the effect of the long-term use of TPIP on exercise capacity in participants with PH-ILD. -To evaluate the effect of the long-term use of TPIP on lung function in participants with PH-ILD. -To evaluate the effects of the long-term use of TPIP on blood biomarkers of disease severity in participants with PH-ILD. -To evaluate the effect of the long-term use of TPIP on the clinical worsening rate in participants with PH-ILD. -To evaluate the effect of the long-term use of TPIP on the exacerbations of underlying lung disease in participants with PH-ILD. -To assess the effect of the long-term use of TPIP on QOL (PRO measures) in participants with PH-ILD. -To further evaluate the PK profile of the long-term use of TPIP in participants with PH-ILD.

Conditions and MedDRA coding

Pulmonary Hypertension Associated with Interstitial Lung Disease

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male and female participants who completed the end of treatment visit in Study INS1009-211, or any other lead-in PH-ILD TPIP study. Participants for whom the OLE study was not available at the time of their completion of the lead-in study are eligible for enrolment within one year of their lead-in end of treatment visit. 2. Complete baseline screening assessments to confirm eligibility to participate if more than 30 days have elapsed since the end of the study visit in Study INS1009-211, or any other lead-in PH-ILD TPIP study. Requirements for baseline screening assessments are located in Section 4.1.1.1. of the Protocol 3. Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 1

1. 1. Participants who experienced any hypersensitivity or adverse drug reaction or were withdrawn early/discontinued in a previous PH-ILD TPIP study, which in the opinion of the Investigator, could indicate that continued treatment with TPIP may present an unreasonable risk for the participant. 2. Initiation of parenteral administration of prostacyclin analogues (eg, TRE, epoprostenol) since the completion of Study INS1009-211 or other TPIP studies. Initiation of inhaled prostacyclin analogues (eg, TRE [Tyvaso] or iloprost) and oral prostacyclin analogues (eg, TRE [Orenitram]) or receptor agonists (eg, selexipag) are permitted if stopped 24 hours prior to the start of study drug administration. 3. Pregnant or breastfeeding. Male and female participants must use contraceptives that are consistent with local regulations regarding the methods of contraception for those participating in clinical studies (contraceptive guidance is located in Section 10.4). Female participants of childbearing potential must have a negative urine pregnancy test result at trial entry before the first dose of study drug. Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.4.2 and Section 8.3.5. 4. Any medical or psychological condition, including relevant laboratory abnormalities at screening that, in the opinion of the Investigator, suggest a new and/or insufficiently understood disease that may present an unreasonable risk to the study participant as a result of participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency and severity of TEAEs during the study.

Secondary endpoints 9

1. Change from pre-OLE baseline* to Month 6, Month 12, Month 18, and Month 24 in 6MWD (absolute and relative).
2. Change from pre-OLE baseline* to Month 6, Month 12, Month 18, and Month 24 in FVC, FVC%, FEV1, FEV1%, and FEF25-75% (absolute and relative).
3. Change from pre-OLE baseline* to Month 6, Month 12, Month 18, and Month 24 in the concentration of NT-proBNP in blood.
4. Change from pre-OLE baseline* to Month 12 and Month 24 in DLCO (absolute and relative).
5. Annualized rate of clinical worsening events. Clinical worsening is defined as one of the following: ---Hospitalization due to a cardiopulmonary indication ---Lung transplantation ---Death from any cause ---Decrease in 6MWD ≥ 15% from baseline, directly related to disease under study, at 2 consecutive visits at least 24 hours apart ---Need for additional PH therapy.
6. Annualized clinical worsening event rate defined as the total number of clinical worsening events that occurred during the treatment period divided by the total number of participant-years during the treatment period.
7. Annualized rate of occurrence of AE-ILDs.
8. Change from OLE baseline in the K-BILD and EQ-5D-5L questionnaire scores at Month 6, Month 12, Month 18, and Month 24.
9. Plasma concentration levels of TP and TRE.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Insmed Inc.

Sponsor organisation

Insmed Inc.

Address

700 Us Highway 202/206

City

Bridgewater

Postcode

08807-1704

Country

United States

Scientific contact point

Organisation

Insmed Inc.

Contact name

Natasha Makulova

Public contact point

Organisation

Insmed Inc.

Contact name

Medical Information

Third parties 7

Locations

4 EU/EEA countries · 17 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 14 files

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

Application history

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