Back to resultsA Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS Study).
Primary Purpose
Pulmonary Arterial Hypertension
Status
Recruiting
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Dose A KER-012
Dose B KER-012
Dose C KER-012
Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary arterial hypertension [PAH]
Eligibility Criteria
Inclusion Criteria: Adult participants ≥ 18 years of age Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH)(PAH) classified by one of the following subgroups: Idiopathic pulmonary arterial hypertension (IPAH); Heritable pulmonary arterial hypertension (HPAH); Associated with drugs and toxins; PAH associated with: Connective tissue disease Congenital systemic-pulmonary intracardiac shunt Has the following hemodynamic parameters that are consistent with the diagnosis of PAH: Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND PVR ≥ 5 Wood Units (400 dyn·sec·cm-5) Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator Must be on a stable PAH background therapy with either an endothelin-receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC) stimulator and/or prostacyclin analogue or receptor agonist (oral/inhaled/SC/intravenous) 6MWD ≥ 150 and ≤ 500 meters at screening Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures Exclusion Criteria: Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after Has uncontrolled systemic hypertension Hemoglobin < 9 g/dL at Screening Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept) Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer
Sites / Locations
- St. Vincent Hospital SydneyRecruiting
- John Hunter HospitalRecruiting
- Macquarie UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Arm 1 (N=20)
Arm 2 (N=20)
Arm 3 (N=20)
Arm 4 (N=30)
Arm Description
KER-012 (Dose A) subcutaneously (SC) (every 4 weeks [Q4W]) Treatment Period: Dose A for 24 weeks; Extension Period: Dose A for another 72 weeks
KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks
KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks
Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks
Outcomes
Primary Outcome Measures
Change from Baseline in PVR (Pulmonary Vascular Resistance)
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy
Secondary Outcome Measures
Change from Baseline in the 6MWD
Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy
Incidence of treatment-emergent adverse events (TEAEs)
A TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that does not necessarily have to have a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Number of treatment-related TEAEs
A treatment-related TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that has a causal relationship with this treatment.
Number of discontinuations due to TEAEs
A treatment-related TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that has a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Change from baseline in Systolic and Diastolic Blood Pressure
Systolic and Diastolic blood pressure measured in mmHg
Change from baseline in QTcF intervals
QTcF intervals measured in msec via ECGs
Incidence of Antidrug Antibodies (ADA)
The amount of ADA measured in serum
Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples
Change from Baseline in NT-proBNP by visit
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- mPAP
Change from Baseline in mean pulmonary artery pressure (mPAP)
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO
Change from Baseline in cardiac output (CO)
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP
Change from Baseline in pulmonary artery wedge pressure (PAWP)
Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy
Proportion of participants who achieved improvement from Baseline in NYHA FC/WHO by visit
Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)
Events that indicate clinical worsening of PAH include death, non-elective PAH-related hospitalization and/or right heart failure inclusive of lung or heart/lung transplant, or atrial septostomy, need to initiate an approved PAH SOC rescue therapy, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD).
Population PK predicted maximum concentration (Cmax) of KER-012
Cmax is a measure of the maximum concentration of a drug in the serum after the dose is given.
Population PK predicted Area under concentration curve (AUC) of KER-012
AUC is a measure of the area under the serum concentration curve after dose is given.
Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy
Proportion of participants who achieve improvement/or maintain low risk in ESC/ ERC 4-strata risk category assessment
Full Information
NCT ID
NCT05975905
First Posted
July 13, 2023
Last Updated
September 15, 2023
Sponsor
Keros Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05975905
Brief Title
A Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS Study).
Official Title
A Randomized, Phase 2, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (TROPOS Study)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
January 31, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Keros Therapeutics, Inc.
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
Study KER-012-A201 is Phase 2, double-blind, randomized, placebo-controlled study to determine the efficacy and safety of KER-012 compared to Placebo in adults with PAH (WHO Group 1 PH) on stable background PAH therapy. The study is divided into the Screening Period, Treatment Period, Extension Period, and Follow-Up Period.
Detailed Description
This is a randomized, phase 2, double-blind, placebo-controlled study of KER-012 in combination with background therapy in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 2:2:2:3 ratio to receive KER-012 (Dose A), KER-012 (Dose B), KER-012 (Dose C), or placebo by subcutaneous injection (SC) every 4 weeks for a period of 24 weeks in the placebo-controlled treatment period of the study while on background therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and safety parameters. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 72-week extension period in which KER-012 treated participants will continue to receive their same assigned dose level from the treatment period every 4 weeks and placebo treated participants will receive KER-012 (Dose B) every 4 weeks while on background therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary arterial hypertension [PAH]
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomly assigned in a 2:2:2:3 ratio to 1 of 4 treatment arms.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a double-blind study in which treatment assignment will be blinded for the Investigators and any personnel (other than the unblinded pharmacist or designee) involved with the study conduct or evaluation at the investigational sites, the CRO, and the Sponsor.
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 (N=20)
Arm Type
Experimental
Arm Description
KER-012 (Dose A) subcutaneously (SC) (every 4 weeks [Q4W]) Treatment Period: Dose A for 24 weeks; Extension Period: Dose A for another 72 weeks
Arm Title
Arm 2 (N=20)
Arm Type
Experimental
Arm Description
KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks
Arm Title
Arm 3 (N=20)
Arm Type
Experimental
Arm Description
KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks
Arm Title
Arm 4 (N=30)
Arm Type
Placebo Comparator
Arm Description
Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks
Intervention Type
Biological
Intervention Name(s)
Dose A KER-012
Intervention Description
Dose A KER-012 (Q4W);
Intervention Type
Biological
Intervention Name(s)
Dose B KER-012
Intervention Description
Dose B KER-012 (Q4W);
Intervention Type
Biological
Intervention Name(s)
Dose C KER-012
Intervention Description
Dose C KER-012 (Q4W);
Intervention Type
Biological
Intervention Name(s)
Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks
Intervention Description
Treatment Period (24 weeks): Placebo SC (Q4W) Extension Period (72 weeks after Placebo treatment): KER-012 (Dose B) SC (Q4W)
Primary Outcome Measure Information:
Title
Change from Baseline in PVR (Pulmonary Vascular Resistance)
Description
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
Change from Baseline in the 6MWD
Description
Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
A TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that does not necessarily have to have a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Number of treatment-related TEAEs
Description
A treatment-related TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that has a causal relationship with this treatment.
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Number of discontinuations due to TEAEs
Description
A treatment-related TEAE is any untoward medical occurrence in a study participant occurring after the initiation of a study treatment that has a causal relationship with this treatment. A TEAE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Change from baseline in Systolic and Diastolic Blood Pressure
Description
Systolic and Diastolic blood pressure measured in mmHg
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Change from baseline in QTcF intervals
Description
QTcF intervals measured in msec via ECGs
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Incidence of Antidrug Antibodies (ADA)
Description
The amount of ADA measured in serum
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples
Description
Change from Baseline in NT-proBNP by visit
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- mPAP
Description
Change from Baseline in mean pulmonary artery pressure (mPAP)
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO
Description
Change from Baseline in cardiac output (CO)
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP
Description
Change from Baseline in pulmonary artery wedge pressure (PAWP)
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy
Description
Proportion of participants who achieved improvement from Baseline in NYHA FC/WHO by visit
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)
Description
Events that indicate clinical worsening of PAH include death, non-elective PAH-related hospitalization and/or right heart failure inclusive of lung or heart/lung transplant, or atrial septostomy, need to initiate an approved PAH SOC rescue therapy, or functional deterioration (worsened WHO Functional Class AND 15% decrease in 6MWD).
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Title
Population PK predicted maximum concentration (Cmax) of KER-012
Description
Cmax is a measure of the maximum concentration of a drug in the serum after the dose is given.
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Population PK predicted Area under concentration curve (AUC) of KER-012
Description
AUC is a measure of the area under the serum concentration curve after dose is given.
Time Frame
Through week 24 (primary treatment period) and Through week 96 (extension period)
Title
Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy
Description
Proportion of participants who achieve improvement/or maintain low risk in ESC/ ERC 4-strata risk category assessment
Time Frame
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants ≥ 18 years of age
Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH)(PAH) classified by one of the following subgroups:
Idiopathic pulmonary arterial hypertension (IPAH);
Heritable pulmonary arterial hypertension (HPAH);
Associated with drugs and toxins;
PAH associated with:
Connective tissue disease
Congenital systemic-pulmonary intracardiac shunt
Has the following hemodynamic parameters that are consistent with the diagnosis of PAH:
Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND
Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND
PVR ≥ 5 Wood Units (400 dyn·sec·cm-5)
Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator
Must be on a stable PAH background therapy with either an endothelin-receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC) stimulator and/or prostacyclin analogue or receptor agonist (oral/inhaled/SC/intravenous)
6MWD ≥ 150 and ≤ 500 meters at screening
Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures
Exclusion Criteria:
Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease
Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease
Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after
Has uncontrolled systemic hypertension
Hemoglobin < 9 g/dL at Screening
Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment
Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis
Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study
Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept)
Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Keros Therapeutics, Inc.
Phone
+1 617 3146297
Email
clinicalstudies@kerostx.com
Facility Information:
Facility Name
St. Vincent Hospital Sydney
City
Darlinghurst
ZIP/Postal Code
2010
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site PI
Facility Name
John Hunter Hospital
City
New Lambton Heights
ZIP/Postal Code
2305
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site PI
Facility Name
Macquarie University
City
Sydney
ZIP/Postal Code
2095
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site PI
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS Study).
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