The aim of the present study is to investigate whether selexipag could be helpful to treat patients with another form of PH called sarcoidosis-associated pulmonary hypertension (SAPH).
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pulmonary Vascular Resistance (PVR) on Study Intervention up to Week 26, 2-5h
post dose. PVR is measured by right heart
catheterization (RHC) and expressed as percent of baseline value.
Secondary outcome
No secondary outcome measures, rest of outcomes is exploratory.
Background summary
Pulmonary hypertension (PH) is a pathophysiological disorder that may involve
multiple clinical conditions and can complicate several cardiovascular and
respiratory diseases. Sarcoidosis is a multisystemic disorder that is
characterized by non-caseating granulomas which are present in multiple
tissues, particularly in the lung and lymphatic system. Severe untreated
pulmonary hypertension (PH) carries a poor prognosis and is associated with
higher mortality in participants with interstitial lung
diseases and sarcoidosis. While there is no approved treatment for SAPH,
PH-specific treatments are frequently used. Selexipag is a selective, orally
available and long-acting non-prostanoid agonist of the prostacyclin receptor
(prostacyclin [IP] receptor) for the treatment of patients with PAH. The
rationale for this study is based on the unmet medical need for new therapeutic
options for participants with SAPH and is supported by the established efficacy
and safety of selexipag in the PAH indication, the shared pathomechanism
between SAPH and PAH, and the available data on the efficacy and safety of
PH-specific therapies in SAPH.
Study objective
The aim of the present study is to investigate whether selexipag could be
helpful to treat patients with another form of PH called sarcoidosis-associated
pulmonary hypertension (SAPH).
Study design
This study consists of screening period, main observation period and double
blind extension period and safety follow-up period. The duration of individual
participation in the study will be different for each individual participant
(between approximately 15 months and up to approximately 3.5 years) and will
depend on the time of each participant*s individual date of entering the study
and the total recruitment time. The efficacy assessments include right heart
catheterization (RHC), assessment of exercise capacity, dyspnea, pulmonary
function tests, etc. Safety and tolerability will be evaluated throughout the
study and includes review of concomitant medications and adverse events (AEs),
clinical laboratory tests, 12-lead electrocardiogram (ECG), vital signs,
physical examination, and pregnancy testing.
Intervention
Selexipag 200 micro gram (µg): Oral tablets containing 200 µg of selexipag.
Depending on the iMTD, participants will receive 1 (200 µg) to 8 (1600 µg)
tablets at each administration.
Study intervention will be up-titrated to allow each participant to reach their
individual maximum tolerated dose (iMTD), in the range of 200 µg to1600 µg (ie,
1 to 8 tablets) bid/qd. Dosing frequency will be bid, except for participants
with moderate hepatic impairment (Child-Pugh B) or who are concomitantly taking
(a) moderate CYP2C8 inhibitor(s), who receive study intervention qd. The dose
will be uptitrated by the investigator/delegate in
200 µg bid/qd increments at weekly intervals during scheduled TCs until
reaching the iMTD. If the dose regimen is not well tolerated or symptoms cannot
be fully managed with symptomatic treatment, the duration of the titration step
can be prolonged to 2 weeks. If needed, the dose can be reduced by 200 µg
bid/qd.
Placebo: Oral tablets without active compound. Participants can receive 1 to 8
tablets at each administration.The comparator will be administered similarly to
the experimental intervention.
Study burden and risks
Severe untreated pulmonary hypertension (PH) carries a poor prognosis and is
associated with higher mortality in participants with interstitial lung
diseases and sarcoidosis. While there is no approved treatment for SAPH,
PH-specific treatments are frequently used. Selexipag is a selective, orally
available and long-acting non-prostanoid agonist of the prostacyclin receptor
(prostacyclin [IP] receptor) for the treatment of patients with PAH. The
rationale for this study is based on the unmet medical need for new therapeutic
options for participants with SAPH and is supported by the established efficacy
and safety of selexipag in the PAH indication, the shared pathomechanism
between SAPH and PAH, and the available data on the efficacy and safety of
PH-specific therapies in SAPH.
Side effects of standard of care, side effects of selexipag, side effects of
assessments and unknown risks may occur. Safety and tolerability will be
evaluated throughout the study from signing of the informed consent form
onwards until the last studyrelated activity (end of study/early withdrawal).
The dosage of selexipag will be up-titrated in 200 µg bid/qd increments at
weekly intervals during scheduled TCs until reaching the iMTD. If the dose
regimen is not well tolerated or symptoms cannot be fully managed with
symptomatic treatment, the duration of the titration step can be prolonged to 2
weeks. If needed, the dose can be reduced by 200 µg bid/qd. The decision to not
further up-titrate the dose will be based on the investigator*s medical
judgment based on the occurrence and severity of typical pharmacological
effects of IP receptor agonists and the participant*s individual tolerability.
An IDMC will be established to monitor the safety of subjects and will review
data in an unblinded manner on a regular basis to ensure the continuing safety
of the subjects enrolled in this study and to evaluate whether efficacy
objectives are met. The IDMC will review the data and make recommendations to
the sponsor Committee, which will be responsible for identifying appropriate
actions based on the recommendations of the IDMC.
Any clinically significant abnormalities persisting at the end of the
study/early withdrawal will be followed by the investigator until resolution or
until a clinically stable endpoint is reached. Safety assessments will be based
on medical review of AE reports and the results of vital sign measurements,
ECGs, physical examinations, clinical laboratory tests, and other safety
evaluations.
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Graaf Engelbertlaan 75
Breda 4837 DS
NL
Listed location countries
Age
Inclusion criteria
- Male or female
-18 to 75 years of age, inclusive
- Confirmed diagnosis of sarcoidosis as per ATS criteria
- Sarcoidosis-associated precapillary PH, confirmed by RHC (at rest) within 90
days prior to randomization.
- PH severity according to modified WHO FC II-IV at Screening and
randomization; participants in WHO FC IV must be in a stable condition and able
to perform a 6MWT.
- Either not receiving PH-specific treatment, or receiving PH-specific oral
monotherapy (ie, riociguat or PDE5i or ERA); if on oral PH-specific monotherapy
treatment has to be stable (ie, no introduction of new therapies or changes in
dose) for at least 90 days prior to both the RHC qualifying for enrollment and
randomization.
- Stable sarcoidosis treatment regimen, ie, no new specific anti inflammatory
treatment for sarcoidosis for at least 90 days, and stable dose(s) for at least
30 days prior to both the RHC qualifying for enrollment and randomization.
- 6MWD between 50 and 450 m both at Screening and at the time of randomization.
- Forced vital capacity (FVC) >50% of predicted at Screening.
- FEV1/FVC >=60%, or if FEV1/FVC <60% then FEV1 must be >=60% of predicted at
Screening.
- Women of childbearing potential must have a negative pregnancy test at
screening and randomization, must agree to undertake monthly urine pregnancy
tests, and to practice an acceptable method of contraception and agree to
remain on an acceptable method while receiving study intervention and until 30
days after last dose of study intervention.
- A woman using oral contraceptives must have been using this method for at
least 1 month prior to randomization.
Exclusion criteria
- PH due to left heart disease (PAWP >15 mmHg).
- History of left heart failure (LHF) as assessed by the investigator including
cardiomyopathies and cardiac sarcoidosis, with a left ventricular ejection
fraction (LVEF) <40%.
- Treatment with prostacyclin, prostacyclin analogues or IP receptor agonists
(ie, selexipag) within 90 days prior to randomization and/or prior to the RHC
qualifying for enrollment, except those given at vasodilator testing during RHC.
- SBP <90 mmHg at Screening or at randomization.
- Included on a lung transplant list or planned to be included until Visit 6 /
Week 39.
- Change in dose or initiation of new diuretics and/or calcium channel blockers
within 1 week prior to RHC qualifying for enrollment.
- Received an investigational intervention or used an invasive investigational
medical device within 90 days prior to randomization.
- Any condition for which, in the opinion of the investigator, participation
would not be in the best interests of the participant (eg, compromise
wellbeing), or that could prevent, limit, or confound the protocol-specified
assessments.
- Any acute or chronic impairment that may influence the ability to comply with
study requirements such as to perform RHC, a reliable and reproducible 6MWT
(eg, use of walking aids such as cane, walker, etc.), or lung function tests.
- Any other criteria as per selexipag Summary of Product Characteristics
(SmPC).
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 |
|---|---|
| EudraCT | EUCTR2018-004887-74-NL |
| ClinicalTrials.gov | NCT03942211 |
| CCMO | NL69964.056.19 |