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).

Phase 2

Active, not recruiting

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Biological: Dose C KER-012; Biological: Dose A KER-012; Biological: Dose B KER-012; Biological: Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks

• Registration Number: NCT05975905
• Lead Sponsor: Keros Therapeutics, Inc.

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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2023-07-13
• Study First Submitted QC: 2023-07-27
• Study First Posted: 2023-08-04
• Study Start: 2023-10-17
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-04
• Primary Completion: 2025-06-30
• Study Completion: 2027-01-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 90

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3 (N=20)	Dose C KER-012	KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks
Arm 1 (N=20)	Dose A KER-012	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 2 (N=20)	Dose B KER-012	KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks
Arm 4 (N=30)	Dose B KER-012	Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks
Arm 4 (N=30)	Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks	Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks

Primary Outcome Measures

Name	Time	Method
Change from Baseline in PVR (Pulmonary Vascular Resistance)	Baseline and Week 24	Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background pulmonary arterial hypertension (PAH) therapy

Secondary Outcome Measures

Name	Time	Method
Change from baseline in QTcF intervals	Through week 24 (primary treatment period) and Through week 96 (extension period)	QTcF intervals measured in msec via ECGs
Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	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	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	Change from Baseline in mean pulmonary artery pressure (mPAP)
Incidence of treatment-emergent adverse events (TEAEs)	Through week 24 (primary treatment period) and Through week 96 (extension period)	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.
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	Change from Baseline in cardiac output (CO)
Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	Proportion of participants who achieved improvement from Baseline in NYHA FC/WHO by visit
Change from Baseline in the 6MWD	Through week 24 (primary treatment period) and Through week 96 (extension period)	Evaluate the effect of KER-012 on exercise capacity compared to Placebo in participants on background PAH therapy
Incidence of Antidrug Antibodies (ADA)	Through week 24 (primary treatment period) and Through week 96 (extension period)	The amount of ADA measured in serum
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	Change from Baseline in pulmonary artery wedge pressure (PAWP)
Number of treatment-related TEAEs	Through week 24 (primary treatment period) and Through week 96 (extension period)	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	Through week 24 (primary treatment period) and Through week 96 (extension period)	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	Through week 24 (primary treatment period) and Through week 96 (extension period)	Systolic and Diastolic blood pressure measured in mmHg
Population PK predicted maximum concentration (Cmax) of KER-012	Through week 24 (primary treatment period) and Through week 96 (extension period)	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	Through week 24 (primary treatment period) and Through week 96 (extension period)	AUC is a measure of the area under the serum concentration curve after dose is given.
Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	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).
Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy	Up to week 24 (primary treatment period) and up to Week 96 (extension period)	Proportion of participants who achieve improvement/or maintain low risk in ESC/ ERC 4-strata risk category assessment

Trial Locations

Locations (55)

TROPOS Study Site 111; 🇺🇸 Scottsdale, Arizona, United States

TROPOS Study Site 107; 🇺🇸 Tucson, Arizona, United States

Site PI TROPOS Study Site 104; 🇺🇸 Stanford, California, United States

TROPOS Study Site 105; 🇺🇸 Torrance, California, United States

TROPOS Study Site 108; 🇺🇸 Jacksonville, Florida, United States

TROPOS Study Site 100; 🇺🇸 Kansas City, Kansas, United States

TROPOS Study Site 110; 🇺🇸 Louisville, Kentucky, United States

TROPOS Study Site 103; 🇺🇸 Boston, Massachusetts, United States

TROPOS Study Site 109; 🇺🇸 Boston, Massachusetts, United States

TROPOS Study Site 101; 🇺🇸 Ann Arbor, Michigan, United States

TROPOS Study Site 115; 🇺🇸 Saint Louis, Missouri, United States

TROPOS Study Site 114; 🇺🇸 Albuquerque, New Mexico, United States

TROPOS Study Site 113; 🇺🇸 Cincinnati, Ohio, United States

TROPOS Study Site 106; 🇺🇸 Charleston, South Carolina, United States

TROPOS Study Site 112; 🇺🇸 Dallas, Texas, United States

TROPOS Study Site 102; 🇺🇸 Houston, Texas, United States

TROPOS Study Site 805; 🇦🇺 Melbourne, Victoria, Australia

TROPOS Study Site 807; 🇦🇺 Auchenflower, Australia

TROPOS Study Site 804; 🇦🇺 Camperdown, Australia

TROPOS Study Site 800; 🇦🇺 Darlinghurst, Australia

TROPOS Study Site 803; 🇦🇺 New Lambton Heights, Australia

TROPOS Study Site 801; 🇦🇺 Sydney, Australia

TROPOS Study Site 200; 🇧🇷 Blumenau, Brazil

TROPOS Study Site 202; 🇧🇷 Porto Alegre, Brazil

TROPOS Study Site 201; 🇧🇷 São Paulo, Brazil

TROPOS Study Site 320; 🇫🇷 Le Kremlin-Bicêtre, France

TROPOS Study Site 341; 🇩🇪 Giesen, Germany

TROPOS Study Site 340; 🇩🇪 Hannover, Germany

TROPOS Study Site 343; 🇩🇪 Heidelberg, Germany

TROPOS Study Site 344; 🇩🇪 Homburg, Germany

TROPOS Study Site 342; 🇩🇪 Leipzig, Germany

TROPOS Study Site 345; 🇩🇪 Regensburg, Germany

TROPOS Study Site 881; 🇰🇷 Incheon, Korea, Republic of

TROPOS Study Site 883; 🇰🇷 Seoul, Korea, Republic of

TROPOS Study Site 882; 🇰🇷 Seoul, Korea, Republic of

TROPOS Study Site 880; 🇰🇷 Seoul, Korea, Republic of

TROPOS Study Site 704; 🇵🇱 Gdańsk, Poland

TROPOS Study Site 701; 🇵🇱 Kraków, Poland

TROPOS Study Site 702; 🇵🇱 Otwock, Poland

TROPOS Study Site 703; 🇵🇱 Poznań, Poland

TROPOS Study Site 706; 🇵🇱 Poznań, Poland

TROPOS Study Site 705; 🇵🇱 Łódź, Poland

TROPOS Study Site 403; 🇵🇹 Almada, Portugal

TROPOS Study Site 402; 🇵🇹 Coimbra, Portugal

TROPOS Study Site 400; 🇵🇹 Lisboa, Portugal

TROPOS Study Site 401; 🇵🇹 Porto, Portugal

TROPOS Study Site 412; 🇪🇸 Barcelona, Spain

TROPOS Study Site 413; 🇪🇸 Barcelona, Spain

TROPOS Study Site 410; 🇪🇸 Madrid, Spain

TROPOS Study Site 411; 🇪🇸 Santander, Spain

TROPOS Study Site 891; 🇨🇳 Kaohsiung, Taiwan

TROPOS Study Site 890; 🇨🇳 Taipei, Taiwan

TROPOS Study Site 441; 🇬🇧 Glasgow, United Kingdom

TROPOS Study Site 442; 🇬🇧 London, United Kingdom

TROPOS Study Site 440; 🇬🇧 London, United Kingdom