Study of Efficacy and Safety of LTP001 in Pulmonary Arterial Hypertension

• ClinicalTrials.gov Identifier: NCT05135000
• Recruitment Status: Recruiting
• First Posted: November 26, 2021
• Last Update Posted: February 24, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pulmonary Arterial Hypertension	Drug: LTP001; Drug: Placebo	Phase 2

Detailed Description:

This is a non-confirmatory, randomized, subject- and investigator-blinded, placebo controlled study of LTP001 in PAH participants. Approximately 44 male and female adults with PAH participants will be randomized in a 3:1 ratio of LTP001 active dose to placebo. Participants will be screened for up to 8 weeks followed by 24 weeks of daily dosing with visits approximately every 4 weeks. One follow up visit will also be the end of study visit and occurs approximately 30 days after the end of treatment. Total study duration is approximately 37 weeks from start of screening to end of study visit. If a participant continues into the open-label extension study, then the follow-up visit may be skipped.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Participant- and Investigator-blinded, Placebo-controlled Study to Investigate Efficacy, Safety, and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension
• Actual Study Start Date: June 30, 2022
• Estimated Primary Completion Date: July 10, 2024
• Estimated Study Completion Date: July 10, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: LTP001; Participants will receive LTP001 orally once daily in the morning for approximately 24 weeks	Drug: LTP001; LTP001 will be administered orally once daily in the morning
Placebo Comparator: Placebo; Participants will receive LTP001 placebo capsules matching LTP001 orally once daily in the morning for approximately 24 weeks	Drug: Placebo; Placebo to LTP001 will be administered once daily in the morning

Outcome Measures

Primary Outcome Measures :

1. Change from baseline right heard catheterization Pulmonary vascular resistance (PVR) at week 25 [ Time Frame: Baseline, week 25 ]
   PVR defined as the resistance against blood flow from the pulmonary artery to the left atrium measured in dyn.s.cm-5

Secondary Outcome Measures :

1. Change from baseline in Six Minute Walk Distance (6MWD) [ Time Frame: Baseline, weeks 13 and 25 ]
   6MWD test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes
2. Change from baseline in Right Ventricle (RV) pressures at week 25 [ Time Frame: Baseline, Week 25 ]
   The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including RV pressures.
3. Change from baseline in pulmonary capillary wedge pressure at week 25 [ Time Frame: Baseline, Week 25 ]
   The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including pulmonary capillary wedge pressure (PCWP).
4. Change from baseline in pulmonary artery pressures at week 25 [ Time Frame: Baseline, Week 25 ]
   The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including pulmonary artery pressure.
5. Change from baseline in Cardiac Output (CO) at week 25 [ Time Frame: Week 25 ]
   The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Cardiac Output (CO).
6. Change from baseline in tricuspid annular plane systolic excursion (TAPSE) [ Time Frame: Baseline, weeks 5, 13 and 25 ]
   Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Plane Sys Excursion (TAPSE) are to be assessed with echocardiography.
7. Change from baseline in tricuspid annular systolic velocity (TASV) [ Time Frame: Baseline, weeks 5, 13 and 25 ]
   Key Right Ventricular (RV) function endpoints such as tricuspid annular systolic velocity (TASV) are to be assessed with echocardiography.
8. Change from baseline of peak velocity of excursion (RV S') [ Time Frame: Baseline, weeks 5, 13 and 25 ]
   Key Right Ventricular (RV) function endpoints such as peak velocity of excursion (RV S') are to be assessed with echocardiography.
9. Change from baseline in fractional area change (FAC) [ Time Frame: Baseline, weeks 5, 13 and 25 ]
   Key Right Ventricular (RV) function endpoints such as RV fractional area change (RV FAC) are to be assessed with echocardiography.
10. Change from baseline in EmPHasis-10 [ Time Frame: Baseline, weeks 13 and 25 ]
    emPHasis-10 is a questionnaire with 10 questions and is designed to determine how pulmonary hypertension affects a participant's life.
11. Change from baseline in PAH-SYMPACT [ Time Frame: Baseline, weeks 13 and 25 ]
    PAH-SYMPACT is a questionnaire used to assess pulmonary arterial hypertension symptoms and their impact.
12. Maximum Observed Blood Concentrations (Cmax) for LTP001 [ Time Frame: Weeks 1 and 25 ]
    The maximum (peak) observed blood drug concentration after single dose administration (ng x mL-1)
13. Time to Reach Maximum Blood Concentrations (Tmax) of LTP001 [ Time Frame: Weeks 1 and 25 ]
    The time to reach maximum (peak) blood drug concentration after single dose administration (h)
14. Time to Clinical Worsening [ Time Frame: Baseline to Week 29 ]

    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
    • Disease progression
    • Significant drop in six minute walk distance
15. Change from baseline in N-terminal fragment of the prohormone B-type natriuetic peptide (NT-ProBNP) [ Time Frame: Baseline to Week 29 ]
    NT-proBNP is a blood biomarker to assess right ventricular distress.

Eligibility Criteria

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

Criteria

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).

Additional protocol-defined inclusion / exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

Locations

Argentina

Novartis Investigative Site; Recruiting

Caba, Buenos Aires, Argentina, C1025ABI

Germany

Novartis Investigative Site; Recruiting

Berlin, Germany, 13353

Novartis Investigative Site; Recruiting

Dresden, Germany, 01307

Novartis Investigative Site; Recruiting

Heidelberg, Germany, 69120

Netherlands

Novartis Investigative Site; Recruiting

Amsterdam, Netherlands, 1081

Poland

Novartis Investigative Site; Recruiting

Lodz, Poland, 91-347

Novartis Investigative Site; Recruiting

Wroclaw, Poland, 50-556

Spain

Novartis Investigative Site; Recruiting

Barcelona, Catalunya, Spain, 08036

Novartis Investigative Site; Recruiting

Madrid, Spain, 28041

United Kingdom

Novartis Investigative Site; Recruiting

Sheffield, South Yorkshire, United Kingdom, S10 2JF

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05135000
• Other Study ID Numbers: CLTP001A12201
• First Posted: November 26, 2021
• Last Update Posted: February 24, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Pulmonary Hypertension

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases