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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05135000

Enrollment

Registered

2021-11-26

Start date

2022-06-30

Completion date

2024-04-25

Last updated

2026-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Hypertension

Brief summary

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.

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.

Interventions

DRUGLTP001

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

DRUGPlacebo

Placebo to LTP001 was administered once daily in the morning

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Right Heard Catheterization Pulmonary Vascular Resistance (PVR) at Week 25	Baseline, 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

Secondary

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

Countries

Argentina, Germany, Netherlands, Poland, Spain, United Kingdom, United States

Participant flow

Pre-assignment details

A total of 56 participants were screened for the study. Out of these, 47 participants were randomized.

Participants by arm

Arm	Count
LTP001 Participants received LTP001, 6 mg, oral capsules, once daily in the morning for approximately 24 weeks	35
Placebo Participants received LTP001 placebo capsules matching LTP001 orally once daily in the morning for approximately 24 weeks	12
Total	47

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	2	0
Overall Study	Lost to Follow-up	1	0
Overall Study	Study Terminated by Sponsor	6	3

Baseline characteristics

Characteristic	LTP001	Placebo	Total
Age, Continuous	45.3 Years STANDARD_DEVIATION 13.03	45.3 Years STANDARD_DEVIATION 13.78	45.3 Years STANDARD_DEVIATION 13.07
Age, Customized 18 - <65	32 Participants	11 Participants	43 Participants
Age, Customized 65 - <85	3 Participants	1 Participants	4 Participants
Race/Ethnicity, Customized American Indian or Alaska	2 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized Asian	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized White	32 Participants	11 Participants	43 Participants
Sex: Female, Male Female	29 Participants	10 Participants	39 Participants
Sex: Female, Male Male	6 Participants	2 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 35	0 / 12	0 / 47
other Total, other adverse events	20 / 35	7 / 12	27 / 47
serious Total, serious adverse events	5 / 35	2 / 12	7 / 47

Outcome results

Primary

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

Time frame: Baseline, Week 25