Clinical trial NCT05764265: Extension Study of Efficacy and Safety of LTP001 in Pulmonary Arterial Hypertension Participants
Official title: An Open-label Extension Study to Investigate Efficacy, Safety and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary Hypertension
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-03-10
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the long-term safety and efficacy profile of LTP001 in participants with pulmonary arterial hypertension (PAH). The study offers participants who had completed the CLTP001A12201 double-blind parent study in PAH an opportunity to receive LTP001 (whether they were on LTP001 or not). Unblinding of the treatment received in CLTP001A12201 is generally not needed, but can occur on request by the investigator.

Detailed description: This is a non-randomized, open-label extension study of LTP001 for participants with PAH who complete the parent study CLTP001A12201. Eligible participants will be presented with the opportunity to enroll in the extension study at the end of treatment visit of the parent study. Participants in the extension study will receive a once daily dose of LTP001 for 52 weeks regardless of their parent study treatment (i.e. LTP001 or placebo). Visits to assess the safety, tolerability and efficacy of LTP001 will take place at Weeks 5, 13, 26, 39 and 52, including a right heart catheterization at Week 26 and a 6-minute walk test and echocardiography at Weeks 26 and 52. Participants will have safety follow-up phone calls at week 9 and 17, and may be invited for unscheduled assessments at the site if deemed necessary. At Week 56, approximately 30 days after the treatment period, participants will have one safety follow-up phone call. The safety and efficacy profile of LTP001 observed in this extension study as well as the parent study will determine the continuation of the extension study.

Eligibility criteria: Inclusion Criteria:

* Written informed consent must be obtained before any assessment is performed.
* Participant is currently completing the Novartis-sponsored study CLTP001A12201 in PAH and completed key efficacy and safety procedures up to the end of treatment of the core study, without meeting discontinuation criteria in the core study.
* Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
* In the opinion of the Investigator would benefit from LTP001 treatment.

Exclusion Criteria:

* History of hypersensitivity to the study treatment.
* Sexually active males not committing to condom use precautions: sexually active males must use a condom during intercourse while taking drug and for 24 hours after stopping study medication and should not father a child in this period nor donate sperm. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
* Required or planned transplant or heart/lung surgery.
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and until EOT visit (2 weeks post-last treatment). Highly effective contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
* Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant
* Use of oral, estrogen and progesterone, injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.

In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
* Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity or execution of study procedures such as 6MWT (e.g., angina pectoris, claudication, musculoskeletal disorder, need for walking aids).
* Permanent discontinuation of Novartis drug in the core efficacy study due to toxicity or disease progression despite active treatment, non-compliance to study procedures, withdrawal of consent or any other reason.

Primary outcomes:
measure: Number of participants with AEs and SAEs
timeFrame: 52 weeks
Secondary outcomes:
measure: Change from baseline right heart catheterization Pulmonary vascular resistance (PVR) at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in Right Atrium (RA) pressures at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in mean PosteroAnterior (PA) pressure at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in Pulmonary Capillary Wedge Pressure (PCWP) at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in Cardiac Output (CO) pressures at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in Systemic Vascular Resistance (SVR) at week 26
timeFrame: Baseline, week 26
measure: Change from baseline in Six Minute Walk Distance (6MWD)
timeFrame: Baseline, week 26, week 52
measure: Change from baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)
timeFrame: Baseline, week 26, week 52
measure: Change from baseline in Tricuspid Annular Plane Systolic Velocity (TASV)
timeFrame: Baseline, week 26, week 52
measure: Change from baseline in Peak Velocity of Excursion (RV S') pressures
timeFrame: Baseline, week 26, week 52
measure: Change from baseline in Fractional Area Change (FAC) pressures
timeFrame: Baseline, week 26, week 52
measure: Change from baseline in Quality of Life measured by emPHasis-10 questionnaire
timeFrame: Baseline to Week 52
measure: Change from baseline in Quality of Life measured by PAH-SYMPACT questionnaire
timeFrame: Baseline to Week 52
measure: Time to Clinical Worsening
timeFrame: Baseline to Week 52
measure: Change from baseline in N-terminal fragment of the prohormone B-type natriuretic peptide (NT-ProBNP)
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Pulmonary Associates PA .
state: Arizona
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
state: South Yorkshire
Study officials:
References: