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).

Pulmonary Arterial Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05975905
• Other study ID #: KER-012-A201
• Status: Recruiting
• Phase: Phase 2
• Start date: October 17, 2023
• Est. completion date: January 31, 2027

Study information

• Verified date: June 2024
• Source: Keros Therapeutics, Inc.
• Contact: Keros Therapeutics, Inc.
• Phone: +1 617 3146297
• Email: clinicalstudies[@]kerostx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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. For more information please check https://tropospahstudy.com/

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 31, 2027
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Biological:
• Dose A KER-012
Dose A KER-012 (Q4W);
• Dose B KER-012
Dose B KER-012 (Q4W);
• Dose C KER-012
Dose C KER-012 (Q4W);
• Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks
Treatment Period (24 weeks): Placebo SC (Q4W) Extension Period (72 weeks after Placebo treatment): KER-012 (Dose B) SC (Q4W)

Locations

Country	Name	City	State
Australia	TROPOS Study Site 804	Camperdown
Australia	TROPOS Study Site 800	Darlinghurst
Australia	TROPOS Study Site 805	Melbourne	Victoria
Australia	TROPOS Study Site 803	New Lambton Heights
Australia	TROPOS Study Site 801	Sydney
Germany	TROPOS Study Site 340	Hannover
Germany	TROPOS Study Site 345	Regensburg
Korea, Republic of	TROPOS Study Site 881	Incheon
Korea, Republic of	TROPOS Study Site 880	Seoul
Korea, Republic of	TROPOS Study Site 882	Seoul
Korea, Republic of	TROPOS Study Site 883	Seoul
Poland	TROPOS Study Site 704	Gdansk
Poland	TROPOS Study Site 701	Kraków
Poland	TROPOS Study Site 705	Lódz
Poland	TROPOS Study Site 702	Otwock
Poland	TROPOS Study Site 706	Poznan
Portugal	TROPOS Study Site 403	Almada
Portugal	TROPOS Study Site 402	Coimbra
Portugal	TROPOS Study Site 400	Lisboa
Portugal	TROPOS Study Site 401	Porto
Spain	TROPOS Study Site 412	Barcelona
Spain	TROPOS Study Site 413	Barcelona
Spain	TROPOS Study Site 410	Madrid
Spain	TROPOS Study Site 411	Santander
Taiwan	TROPOS Study Site 891	Kaohsiung
Taiwan	TROPOS Study Site 890	Taipei
United Kingdom	TROPOS Study Site 441	Glasgow
United Kingdom	TROPOS Study Site 440	London
United States	TROPOS Study Site 114	Albuquerque	New Mexico
United States	TROPOS Study Site 101	Ann Arbor	Michigan
United States	TROPOS Study Site 103	Boston	Massachusetts
United States	TROPOS Study Site 109	Boston	Massachusetts
United States	TROPOS Study Site 106	Charleston	South Carolina
United States	TROPOS Study Site 113	Cincinnati	Ohio
United States	TROPOS Study Site 102	Houston	Texas
United States	TROPOS Study Site 100	Kansas City	Kansas
United States	TROPOS Study Site 110	Louisville	Kentucky
United States	TROPOS Study Site 115	Saint Louis	Missouri
United States	TROPOS Study Site 111	Scottsdale	Arizona
United States	Site PI TROPOS Study Site 104	Stanford	California
United States	TROPOS Study Site 105	Torrance	California
United States	TROPOS Study Site 107	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Keros Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Korea, Republic of,  Poland,  Portugal,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline and Week 24
Secondary	Change from Baseline in the 6MWD	Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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.	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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.	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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.	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	Change from baseline in Systolic and Diastolic Blood Pressure	Systolic and Diastolic blood pressure measured in mmHg	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	Change from baseline in QTcF intervals	QTcF intervals measured in msec via ECGs	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	Incidence of Antidrug Antibodies (ADA)	The amount of ADA measured in serum	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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)	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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)	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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)	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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).	Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary	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.	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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.	Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary	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	Up to week 24 (primary treatment period) and up to Week 96 (extension period)