To evaluate the long-term safety and tolerability of inhaled treprostinil in subjects with IPF.
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy will be assessed by evaluating the effect of continued
long-term therapy with inhaled treprostinil on the following
parameters:
• Change in absolute forced vital capacity (FVC)
• Time to clinical worsening (including time to death,
respiratory hospitalization, or >=10% relative decline in
% predicted FVC)
• Time to acute exacerbation of IPF
• Overall survival
• Change in % predicted FVC
• Change in King*s Brief Interstitial Lung Disease (K-BILD)
Questionnaire score
• Change in N-terminal pro-brain natriuretic peptide
(NT-proBNP)
• Change in diffusion capacity of lungs for carbon monoxide
(DLCO)
• Change in resting supplemental oxygen use
Safety will be assessed by reviewing the following parameters:
• Adverse events (AEs) and serious adverse events (SAEs)
• Clinical laboratory parameters
• Vital signs, including saturation of peripheral capillary
oxygenation
• 12-lead electrocardiograms
Secondary outcome
N/A
Background summary
Interstitial lung disease (ILD) encompasses a heterogeneous group of
parenchymal lung diseases that are characterized by significant scarring or
fibrosis of the bronchioles and alveolar sacs within the lungs (Travis 2013,
Seeger 2013). Increased fibrotic tissue in ILD prevents oxygenation and free
gas exchange between the pulmonary capillaries and alveolar sacs. The
symptomatology of ILD is non-specific and covers a wide range of symptoms, and
severity of symptoms can vary substantially among patients. Only 2 therapies
are currently approved by the Food and Drug Administration (FDA) and European
Medicines Agency for ILD indications, nintedanib (Ofev®) and pirfenidone
(Esbriet®). Nintedanib is a kinase inhibitor approved for the
treatment of idiopathic pulmonary fibrosis (IPF), chronic fibrosing ILDs with a
progressive phenotype, and systemic sclerosis-associated ILD (Ofev Prescribing
information 2020, Ofev Summary of Product Characteristics 2021). Pirfenidone
belongs to the pyridone class and is approved for the treatment of IPF (Esbriet
Prescribing information 2019, Esbriet Summary of Product Characteristics 2021).
While results from randomized studies show that nintedanib and pirfenidone slow
the rate of decline in forced vital capacity (FVC), additional treatment
options for IPF are needed as pulmonary fibrosis continues to confer high
morbidity and mortality despite currently available treatments (Montesi 2020,
King 2014). The results of RIN-PH-201 (INCREASE) (Section 1.2.3) in patients
with pulmonary hypertension (PH) associated with ILD (PH-ILD) provide evidence
that inhaled treprostinil may offer a treatment option for patients with IPF.
Study objective
To evaluate the long-term safety and tolerability of inhaled treprostinil in
subjects with IPF.
Study design
This is a Phase 3, multicenter, multinational, open-label extension (OLE) study
for eligible subjects who completed RIN-PF-301 or RIN-PF-303.
Intervention
Daily treatment with inhaled treprostinil using the TD-300 inhalation system.
Study burden and risks
Treprostinil has a long history of safety and efficacy in WHO Group 1 PAH and
is currently marketed as 3 formulations (parenteral
solution, inhalation solution, and oral tablet) in various regions.
Additionally, the recently completed INCREASE study (RIN-PH-201)
demonstrated that inhaled treprostinil is safe and efficacious for the
treatment of PH-ILD. The pulmonary function test safety results from
INCREASE suggest that inhaled treprostinil may provide substantial benefit with
minimal risks for the treatment of IPF.
The TD-300/A has been in use since 01 May 2018. Use of the TD-300/A has
resulted in no occasional, probable, or frequent severe
ADEs. A further analysis of the anticipated ADEs resulting from the risk
mitigation processes, which incorporate the TD-300/A post-market use,
can be found in the TD-300/A IB. The potential benefits of the nebulised
treprostinil solution administered with the TD-300/A in IPF
subjects discussed previously, and the minimal observed risk of the TD-300/A
after more than 4 million exposure days, suggest the
TD-300/A provides substantial benefit with minimal risks for the treatment of
IPF.
Alexander Drive 55TW
Research Triangle Park NC 27709
US
Alexander Drive 55TW
Research Triangle Park NC 27709
US
Listed location countries
Age
Inclusion criteria
1. Subject gives voluntary informed consent to participate in the study.
2. The subject participated in RIN-PF-301 or RIN-PF-303 and had 1 of the
following
applied:
a. Remained on study drug and completed all scheduled study visits
b. Was enrolled in RIN-PF-301 or RIN-PF-303 at the time that the study or study
subject was discontinued by the Sponsor.
3. Women of childbearing potential must be non-pregnant (as confirmed by a
urine
pregnancy test at OLE Entry Visit 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. 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 or postmenopausal are not considered to
be of
reproductive potential.
4. 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.
5. 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. Subject is pregnant or lactating.
2. In the opinion of the Investigator, enrollment in RIN-PF-302 would represent
a risk to the
subject*s overall health.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | CTIS: 2023-504471-25-00 |
| CCMO | NL85188.100.23 |