Extension Study of Efficacy and Safety of LTP001 in Pulmonary Arterial Hypertension Participants

Phase 2TerminatedNCT05764265

Novartis Pharmaceuticals31 enrolled

Overview

The purpose of this study was to measure the long-term safety and efficacy profile of LTP001 in participants with pulmonary arterial hypertension (PAH). The study offered 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 was generally not needed but could occur on request by the investigator.

This was a non-randomized, open-label extension study of LTP001 for participants with PAH who completed the parent Study CLTP001A12201. Eligible participants were 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 were planned to receive a once-daily dose of LTP001 for 52 weeks regardless of their parent study treatment (i.e. LTP001 or placebo). The study duration was planned up to 54 weeks with a treatment duration up to 52 weeks and maximum 2-week transition period from the CLTP001A12201 study. The visit frequency was planned to include visits at Weeks 1, 5, 13, 26, 39, 52, and 54 along with optional visits at the discretion of the Investigators at Weeks 9 and 17. Due to the study termination, no patient reached Week 52. After the termination announcement, following the instruction to immediately stop treatment for all participants, an end-of-treatment (EOT) visit was conducted. Sites were advised to complete protocol-required assessments based on investigator judgement and patient willingness to undergo procedures, with a primary focus on ensuring a safe exit from the study. Most sites performed only a few safety assessments, and only a minimal number of patients completed an echocardiogram.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pulmonary Arterial Hypertension

Interventions

LTP001DRUG

LTP001, 6 mg, was administered orally once daily in the morning

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Written informed consent must have been obtained before any assessment was performed. * Participant was 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 have used 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 was 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 were using highly effective methods of contraception while taking study treatment and until EOT visit (2 weeks post-last treatment). Highly effective contraception methods included: * Total abstinence (when this was in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal were not acceptable methods of contraception. * Female sterilization (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 had 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 have been 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 were considered post-menopausal if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women were considered not of child-bearing potential if they were post-menopausal or had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks prior. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment was she considered not of child bearing potential. * Pregnant or nursing (lactating) women, where pregnancy was 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.

Locations (12)

Pulmonary Associates PA

Mesa, Arizona, United States

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Dresden, Saxony, Germany

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Incidence and severity of adverse events (AEs) by treatment group, including changes in the vital signs, electrocardiogram and laboratory results qualifying and reported as AEs. Due to the study termination, no patient reached Week 52. At the end of treatment visit, final safety assessments were performed.

Time frame: Up to approximately 45 weeks

Secondary Outcomes

Change From Baseline in Average Cardiac Output (CO) at Week 26

Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including CO.

Time frame: Baseline, Week 26

Change From Baseline in Mean Pulmonary Artery (PA) Pressure at Week 26

Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including PA pressure.

Time frame: Baseline, Week 26

Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 26

Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including pulmonary capillary wedge pressure (PCWP).

Time frame: Baseline, Week 26

Change From Baseline in Right Heart Catheterization Pulmonary Vascular Resistance (PVR) at Week 26

PVR was defined as the resistance against blood flow from the pulmonary artery to the left atrium measured in dynes.sec.cm-5.

Time frame: Baseline, Week 26

Change From Baseline in Right Atrium (RA) Pressures at Week 26

The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including RA pressures.

Data from ClinicalTrials.gov

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Novartis Investigative Site

Heidelberg, Germany

Novartis Investigative Site

Amsterdam, North Holland, Netherlands

Novartis Investigative Site

Krakow, Poland

Novartis Investigative Site

Lodz, Poland

Novartis Investigative Site

Wroclaw, Poland

Novartis Investigative Site

Barcelona, Spain

Novartis Investigative Site

Madrid, Spain

...and 2 more locations

Time frame: Baseline, Week 26

Change From Baseline in Systemic Vascular Resistance (SVR) at Week 26

The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including SVR.

Time frame: Baseline, Week 26

Change From Baseline in Six Minute Walk Distance (6MWD)

6MWD test measures the distance that a participant can walk on a flat, hard surface in a period of 6 minutes. Due to the study termination, no patient reached Week 52. At the end of treatment (EOT) visit, final safety assessments were performed based on investigator judgement and patient willingness to undergo procedures.