Study of Efficacy and Safety of LTP001 in Pulmonary Arterial Hypertension

A Randomized, Participant- and Investigator-blinded, Placebo-controlled Study to Investigate Efficacy, Safety, and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension

The purpose of this study was to explore the efficacy and safety of LTP001 in participants with pulmonary arterial hypertension (PAH) to determine if LTP001 had an adequate clinical profile to warrant further clinical development in this indication.

Study Overview

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

Detailed Description

This study was a non-confirmatory, randomized, participant- and investigator-blinded, placebo controlled trial evaluating the efficacy and safety of LTP001 on top of standard of care in participants with PAH.

The study included a screening period of up to 8 weeks, followed by a 24-week treatment phase with daily dosing and visits scheduled approximately every 4 weeks. One follow-up visit, which also served as the end-of-study visit, was conducted approximately 30 days after the conclusion of the treatment phase. The total duration of the study, from the beginning of the screening period to the end-of-study visit, was approximately 37 weeks.

A total of 44 participants were planned to be randomized in a 3:1 ratio to receive either LTP001 6 mg or placebo.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1025ABI
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, 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
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Andalusia
    • Málaga, Andalusia, Spain, 29010
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW3 6PH
    • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Pulmonary Associates PA
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univ Of South Carolina

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• History of PAH belonging to one of the following subgroups of the Clinical Classification Group 1 (WHO):

  • participants with idiopathic pulmonary arterial hypertension (IPAH)
  • Hereditary pulmonary arterial hypertension
  • Congenital heart disease (surgically repaired at least 12 months prior to screening)
  • drug or toxin induced (for example, anorexigen, or methamphetamine use).
• Resting mean pulmonary arterial pressure (mPAP) > 25 mmHg; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure < 15 mmHg, as determined by right heart catheterization within 20 days of randomization.
• Pulmonary Vascular Resistance > 6 Wood units (480 dynes s/cm-5), as determined by right heart catheterization within 20 days of randomization.
• WHO Functional Class II-III

• 6MWD must be between 150 and 550 m (inclusive). The qualifying test needs to be within 20 days of randomization. To meet the above criterion additional six minute walk test (6MWT) may be performed up to a maximum of 3 tests in total prior to dosing; the minimal time difference between two tests should be at least 4 h.

  • Standard of care therapy which is stable at least 6 weeks prior to RHC and qualifying 6MWT assessment within 20 days of randomization. Standard of care includes one or more of the following treatments:
  • prostacyclin analogues and receptor agonists (if I.V., dose adjustments must be within 20% of initial stable dose)
  • endothelin receptor antagonists (ERAs)
  • phosphodiesterase type 5 inhibitors (PDE5i)
  • soluble guanylate cyclase (sGC) stimulators

Exclusion Criteria:

• Participants with pulmonary hypertension (PH) in the Clinical Classification Groups 2-5 (WHO), and any PAH Group 1 subgroups not covered by Inclusion Criterion #4.
• Participants with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease compromising left ventricular function and/or pulmonary venous hypertension or symptomatic coronary disease (non-symptomatic, revascularized coronary artery disease would be acceptable).
• Participants with obstructive lung disease defined as: FEV1/FVC < 60% and FEV1 < 60% of predicted value after bronchodilator administration as well as participants with moderate or severe restrictive lung disease: Total Lung Capacity < 70% of predicted value. Testing must have occurred within 24months of screening. If historical testing is not available, then lung function testing must be conducted during the screening period.
• Acute or chronic impairment (other than dyspnea), which would limit the ability to comply with study requirements, including interference with physical activity and execution of study procedures such as 6MWT (e.g., angina pectoris, claudication, musculoskeletal disorder, multiple sclerosis, need for walking aids).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LTP001; Participants received LTP001, 6 mg, oral capsules, once daily in the morning for approximately 24 weeks	Drug: LTP001; LTP001, 6 mg, was administered orally once daily in the morning
Placebo Comparator: Placebo; Participants received LTP001 placebo capsules matching LTP001 orally once daily in the morning for approximately 24 weeks	Drug: Placebo; Placebo to LTP001 was administered once daily in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Right Heard Catheterization Pulmonary Vascular Resistance (PVR) at Week 25	PVR was defined as the resistance against blood flow from the pulmonary artery to the left atrium measured in dyn.s.cm-5	Baseline, Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Six Minute Walk Distance (6MWD)	6MWD test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes	Baseline, Weeks 13 and 25
Change From Baseline in Right Atrium (RA) Pressures at Week 25	The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including RA pressures.	Baseline, Week 25
Change From Baseline in Pulmonary Capillary Wedge Pressure at Week 25	Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including pulmonary capillary wedge pressure (PCWP).	Baseline, Week 25
Change From Baseline in Mean Pulmonary Artery Pressure at Week 25	Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including pulmonary artery pressure.	Baseline, Week 25
Change From Baseline in Average Cardiac Output (CO) at Week 25	Right heart catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including cardiac output (CO).	Baseline, Week 25
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.	Baseline, Weeks 5, 13, and 25
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.	Baseline, Weeks 5, 13, and 25
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.	Baseline, Weeks 5, 13, and 25
Change From Baseline in Tricuspid Annular Systolic Velocity (TASV)	Key right ventricular (RV) function endpoints such as tricuspid annular systolic velocity (TASV) were assessed with echocardiography.	Baseline, Weeks 5, 13 and 25
Change From Baseline in EmPHasis-10	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.	Baseline, Weeks 13 and 25
Change From Baseline in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT)	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.	Baseline, Weeks 13 and 25
Maximum Observed Blood Concentrations (Cmax) for LTP001	The maximum (peak) observed blood drug concentration after single dose administration.	Day 1 and Week 25 at 15, 45, and 120 minutes post-dose
Time to Reach Maximum Blood Concentrations (Tmax) of LTP001	The time to reach maximum (peak) blood drug concentration after single dose administration.	Day 1 and Week 25 at 15, 45, and 120 minutes post-dose
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	Baseline up to approximately 30 weeks
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.	Baseline to Week 29

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): June 30, 2022
• Primary Completion (Actual): March 20, 2024
• Study Completion (Actual): April 25, 2024

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Estimated): January 13, 2026
• Last Update Submitted That Met QC Criteria: December 18, 2025
• Last Verified: December 1, 2025

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: CLTP001A12201

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