search
Back to results

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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LTP001
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Participant is 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. Participant currently has no evidence of treatment failure, as determined by the investigator, following previous treatment. 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 use 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 is 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 are using highly effective methods of contraception while taking study treatment and until EOT visit (2 weeks post-last treatment). Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have 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 has 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 be 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 are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. Pregnant or nursing (lactating) women, where pregnancy is 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.

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LTP001

Arm Description

Participants will receive LTP001 orally once daily in the morning for approximately 52 weeks

Outcomes

Primary Outcome Measures

Number of patients with AEs and SAEs
Long term safety follow up.

Secondary Outcome Measures

Change from baseline right heart catheterization Pulmonary vascular resistance (PVR) at week 26
PVR defined as the resistance against blood flow from the pulmonary artery to the left atrium measured in dyn·s/cm-5
Change from baseline in Right Atrium (RA) pressures at week 26
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including RA pressures
Change from baseline in mean PosteroAnterior (PA) pressure at week 26
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including PA pressure
Change from baseline in Pulmonary Capillary Wedge Pressure (PCWP) at week 26
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including PCWP
Change from baseline in Cardiac Output (CO) pressures at week 26
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including CO
Change from baseline in Systemic Vascular Resistance (SVR) at week 26
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including SVR
Change from baseline in Six Minute Walk Distance (6MWD)
6MWD test measures the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes
Change from baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Key Right Ventricular endpoints such as TAPSE are to be assessed with electrocardiography
Change from baseline in Tricuspid Annular Plane Systolic Velocity (TASV)
Key Right Ventricular (RV) function endpoints such as TASV are to be assessed with electrocardiography
Change from baseline in Peak Velocity of Excursion (RV S') pressures
Key Right Ventricular (RV) function endpoints such as RV S' are to be assessed with electrocardiography
Change from baseline in Fractional Area Change (FAC) pressures
Key Right Ventricular (RV) function endpoints such FAC are to be assessed with electrocardiography
Change from baseline in Quality of Life measured by emPHasis-10 questionnaire
emPHasis-10 is a questionnaire with 10 questions and is designed to determine how pulmonary hypertension affects a participant's life
Change from baseline in Quality of Life measured by PAH-SYMPACT questionnaire
PAH-SYMPACT is a questionnaire used to assess pulmonary arterial hypertension symptoms and their impact
Time to Clinical Worsening
Time to any of the following: Death Hospital stay greater than 24 hours due to worsening of PAH. Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy Initiation of parenteral prostanoid therapy, chronic oxygen therapy, or any other PAH-specific therapies or need for increase of diuretics for more than 4 weeks due to worsening of PAH Disease progression Significant drop in 6MWD
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

Full Information

First Posted
January 10, 2023
Last Updated
October 9, 2023
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT05764265
Brief Title
Extension Study of Efficacy and Safety of LTP001 in Pulmonary Arterial Hypertension Participants
Official Title
An Open-label Extension Study to Investigate Efficacy, Safety and Tolerability of LTP001 in Participants With Pulmonary Arterial Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 27, 2023 (Actual)
Primary Completion Date
September 29, 2025 (Anticipated)
Study Completion Date
September 29, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to measure the long-term safety and efficacy profile of LTP001 in participants with pulmonary arterial hypertension (PAH). The study offers 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 is generally not needed, but can occur on request by the investigator.
Detailed Description
This is a non-randomized, open-label extension study of LTP001 for participants with PAH who complete the parent study CLTP001A12201. Eligible participants will be 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 will receive a once daily dose of LTP001 for 52 weeks regardless of their parent study treatment (i.e. LTP001 or placebo). Visits to assess the safety, tolerability and efficacy of LTP001 will take place at Weeks 5, 13, 26, 39 and 52, including a right heart catheterization at Week 26 and a 6-minute walk test and echocardiography at Weeks 26 and 52. At Week 56, approximately 30 days after the treatment period, participants will have one safety follow-up phone call. The safety and efficacy profile of LTP001 observed in this extension study as well as the parent study will determine the continuation of the extension study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LTP001
Arm Type
Experimental
Arm Description
Participants will receive LTP001 orally once daily in the morning for approximately 52 weeks
Intervention Type
Drug
Intervention Name(s)
LTP001
Intervention Description
LTP001 will be administered orally once daily in the morning
Primary Outcome Measure Information:
Title
Number of patients with AEs and SAEs
Description
Long term safety follow up.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Change from baseline right heart catheterization Pulmonary vascular resistance (PVR) at week 26
Description
PVR 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 26
Title
Change from baseline in Right Atrium (RA) pressures at week 26
Description
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including RA pressures
Time Frame
Baseline, week 26
Title
Change from baseline in mean PosteroAnterior (PA) pressure at week 26
Description
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including PA pressure
Time Frame
Baseline, week 26
Title
Change from baseline in Pulmonary Capillary Wedge Pressure (PCWP) at week 26
Description
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including PCWP
Time Frame
Baseline, week 26
Title
Change from baseline in Cardiac Output (CO) pressures at week 26
Description
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including CO
Time Frame
Baseline, week 26
Title
Change from baseline in Systemic Vascular Resistance (SVR) at week 26
Description
The Right Heart Catheterization (RHC) assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including SVR
Time Frame
Baseline, week 26
Title
Change from baseline in Six Minute Walk Distance (6MWD)
Description
6MWD test measures the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes
Time Frame
Baseline, week 26, week 52
Title
Change from baseline in Tricuspid Annular Plane Systolic Excursion (TAPSE)
Description
Key Right Ventricular endpoints such as TAPSE are to be assessed with electrocardiography
Time Frame
Baseline, week 26, week 52
Title
Change from baseline in Tricuspid Annular Plane Systolic Velocity (TASV)
Description
Key Right Ventricular (RV) function endpoints such as TASV are to be assessed with electrocardiography
Time Frame
Baseline, week 26, week 52
Title
Change from baseline in Peak Velocity of Excursion (RV S') pressures
Description
Key Right Ventricular (RV) function endpoints such as RV S' are to be assessed with electrocardiography
Time Frame
Baseline, week 26, week 52
Title
Change from baseline in Fractional Area Change (FAC) pressures
Description
Key Right Ventricular (RV) function endpoints such FAC are to be assessed with electrocardiography
Time Frame
Baseline, week 26, week 52
Title
Change from baseline in Quality of Life measured by emPHasis-10 questionnaire
Description
emPHasis-10 is a questionnaire with 10 questions and is designed to determine how pulmonary hypertension affects a participant's life
Time Frame
Baseline to Week 52
Title
Change from baseline in Quality of Life measured by PAH-SYMPACT questionnaire
Description
PAH-SYMPACT is a questionnaire used to assess pulmonary arterial hypertension symptoms and their impact
Time Frame
Baseline to Week 52
Title
Time to Clinical Worsening
Description
Time to any of the following: Death Hospital stay greater than 24 hours due to worsening of PAH. Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy Initiation of parenteral prostanoid therapy, chronic oxygen therapy, or any other PAH-specific therapies or need for increase of diuretics for more than 4 weeks due to worsening of PAH Disease progression Significant drop in 6MWD
Time Frame
Baseline to Week 52
Title
Change from baseline in N-terminal fragment of the prohormone B-type natriuretic peptide (NT-ProBNP)
Description
NT-proBNP is a blood biomarker to assess right ventricular distress
Time Frame
Baseline to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Participant is 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. Participant currently has no evidence of treatment failure, as determined by the investigator, following previous treatment. 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 use 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 is 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 are using highly effective methods of contraception while taking study treatment and until EOT visit (2 weeks post-last treatment). Highly effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Female sterilization (have 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 has 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 be 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 are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy) or total hysterectomy at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. Pregnant or nursing (lactating) women, where pregnancy is 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Facility Information:
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1081
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Lodz
ZIP/Postal Code
91-347
Country
Poland
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

We'll reach out to this number within 24 hrs