OLE study in participants with pulmonary arterial hypertension

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

6 Apr 2023 → ongoing

Decision date (initial)

2024-09-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-505539-11-00

EudraCT number

2022-001951-18

ClinicalTrials.gov

NCT05649748

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the safety and tolerability of the long-term use of TPIP in participants with PAH from studies INS1009 201, INS1009 202, and other lead in studies of TPIP in participants with PAH.

Secondary objectives 1

1. To evaluate the effect of the long-term use of TPIP on exercise capacity, on the clinical status, clinical worsening rate and on the mortality risk in participants with PAH.

Conditions and MedDRA coding

Pulmonary Arterial Hypertension

Study design 5 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Participants who completed the end of treatment visit in Study INS1009 201, Study INS1009 202, or any other lead in PAH 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 201, Study INS1009 202, or any other lead in PAH TPIP in study.
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 9

1. Initiation of parenteral administration of prostacyclin analogues (eg, TRE, epoprostenol) since the completion of studies INS1009 201, INS1009 202 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.
2. QTcF interval > 480 ms on resting ECG at screening, not including participants with right bundle branch block (RBBB) leading to a prolongation of the QRS.
3. Any new ventricular or supraventricular tachyarrhythmia except for paroxysmal atrial fibrillation and any new symptomatic bradycardia.
4. New onset of heart disease including left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant valvular, constrictive, or symptomatic atherosclerotic heart disease (eg, stable angina, myocardial infarction, etc).
5. New evidence of thromboembolic disease as assessed by VQ scan, pulmonary angiography, or pulmonary CT scan.
6. Active and current symptomatic COVID-19 or previous severe disease and/or hospitalization due to COVID-19
7. Current use of cigarettes (as defined by CDC) or e-cigarettes: An adult who has smoked at least 100 cigarettes in his or her lifetime, who smokes either every day or some days
8. Participants who currently inhale marijuana (recreational or medical).
9. Participants who experienced any hypersensitivity or adverse drug reaction or were withdrawn early/discontinued in a previous PAH TPIP study, which, in the opinion of the Investigator, could indicate that continued treatment with TPIP may present an unreasonable risk for the participant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency and severity of TEAEs during the study

Secondary endpoints 4

1. Change from pre-OLE baseline to Month 6, Month 12, Month 18, and Month 24 in 6MWD (absolute and relative), in the concentration of NT proBNP in blood, in the REVEAL Lite 2.0 score, in NYHA/WHO functional capacity class.
2. Annualized rate of clinical worsening events defined as one of the following: - All cause death, or onset of TEAE with a fatal outcome occurring ≤ 14 days after study drug discontinuation. - Hospitalization for right heart failure (for > 48 hours), heart lung or lung transplant, or atrial septostomy
3. Addition (or increase in dose) of specified PAH-specific medications. Combined occurrence of events including a 20% decrease in 6MWD, worsening WHO/NYHA functional capacity class, and appearance of or worsening of signs/symptoms of right heart failure. 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.
4. Plasma concentration levels of TP and TRE

Investigational products

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

Test 3

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

Fraz Ismat

Public contact point

Organisation

Insmed Inc.

Contact name

Medical Information

Third parties 8

Locations

6 EU/EEA countries · 12 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 38 files

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

Application history

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