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

An Open-label Extension Study to Investigate Efficacy, Safety and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: LTP001

Detailed Description

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
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1025ABI
      • Novartis Investigative Site
• Germany
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Novartis Investigative Site
• Poland
  • Krakow, Poland, 31 202
    • Novartis Investigative Site
  • Lodz, Poland, 91-347
    • Novartis Investigative Site
  • Wroclaw, Poland, 50-556
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Málaga, Spain, 29010
    • Novartis Investigative Site
• United Kingdom
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Pulmonary Associates PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LTP001; Participants received LTP001, 6 mg, orally once daily in the morning for approximately 39 weeks	Drug: LTP001; LTP001, 6 mg, was administered orally once daily in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to approximately 45 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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).	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.	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.	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.	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.	Baseline, Week 26, up to 39 weeks (EOT)
Change From Baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)	Key right ventricular (RV) function endpoints such as tricuspid annular plane systolic excursion (TAPSE) were assessed with echocardiography. 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. Only a minimal number of patients completed an echocardiogram (Echo).	Baseline, Week 26, up to 39 weeks (EOT)
Change From Baseline in Tricuspid Annular Plane Systolic Velocity (TASV)	Key right ventricular (RV) function endpoints such as tricuspid annular systolic velocity (TASV) were assessed with echocardiography. 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. Only a minimal number of patients completed an echocardiogram (Echo).	Baseline, Week 26, up to 39 weeks (EOT)
Change From Baseline in Peak Velocity of Excursion (RV S')	Key right ventricular (RV) function per echocardiography. The terms Tricuspid Annular Systolic Velocity (TASV) and Peak Velocity of Excursion (RV S') are synonymous in echocardiography to describe the peak systolic velocity of the lateral tricuspid annulus. Including both TASV and RV S' as separate secondary endpoints was an oversight in the protocol as the data, calculation, and analyses for both (TASV and RV S') are identical. Therefore, the TASV and RV S' data in this results disclosure are the same. 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. Only a minimal number of patients completed an echocardiogram (Echo).	Baseline, Week 26, up to 39 weeks (EOT)
Change From Baseline in Fractional Area Change (FAC)	Key right ventricular (RV) function endpoints such as RV fractional area change (RV FAC) were assessed with echocardiography. 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. Only a minimal number of patients completed an echocardiogram (Echo).	Baseline, Week 26, up to 39 weeks (EOT)
Change From Baseline in Quality of Life Measured by the emPHasis-10 Questionnaire	emPHasis-10 is a questionnaire with 10 questions designed to determine how pulmonary hypertension affects a participant's life. Each item is scored on a scale of 0 to 5, with a total score ranging from 0 to 50. A higher score indicates worse quality of life. 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.	Baseline up to 39 weeks (EOT)
Change From Baseline in Quality of Life Measured by the PAH-SYMPACT Questionnaire	PAH-SYMPACT is a questionnaire used to assess pulmonary arterial hypertension symptoms and their impact. Individual item scores range from 0 to 4. Total score is calculated as the sum of the scores for the individual items divided by the number of items. A higher score indicates more severe symptoms/impacts. 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.	Baseline up to 39 weeks (EOT)
Time to Clinical Worsening	Time to any of the following: Death; Hospital stay greater than 24 hours due to worsening of pulmonary arterial hypertension; Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy; Initiation of parenteral prostanoid therapy, initiation of oxygen therapy, initiation of any other pulmonary arterial hypertension-specific therapies or need for increase of diuretics for more than 4 weeks due to worsening of pulmonary arterial hypertension; Significant drop in six-minute walk distance 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.	Baseline up to 39 weeks (EOT)
Change From Baseline in N-terminal Fragment of the Prohormone B-type Natriuretic Peptide (NT-ProBNP)	NT-proBNP is a blood biomarker to assess right ventricular distress. 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.	Baseline up to 39 weeks (EOT)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Actual): April 26, 2024
• Study Completion (Actual): May 14, 2024

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: March 1, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Pulmonary Arterial Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: CLTP001A12201E1; 2022-002007-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No