Clinical trial NCT05975905: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Keywords: Pulmonary arterial hypertension [PAH]
Lead sponsor: Keros Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-04
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned in a 2:2:2:3 ratio to 1 of 4 treatment arms.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from Baseline in PVR (Pulmonary Vascular Resistance)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Change from Baseline in the 6MWD
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Number of treatment-related TEAEs
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Number of discontinuations due to TEAEs
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Change from baseline in Systolic and Diastolic Blood Pressure
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Change from baseline in QTcF intervals
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Incidence of Antidrug Antibodies (ADA)
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- mPAP
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
measure: Population PK predicted maximum concentration (Cmax) of KER-012
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Population PK predicted Area under concentration curve (AUC) of KER-012
timeFrame: Through week 24 (primary treatment period) and Through week 96 (extension period)
measure: Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy
timeFrame: Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: TROPOS Study Site 111
state: Arizona
city: Tucson
country: United States
facility: TROPOS Study Site 107
state: Arizona
city: Stanford
country: United States
facility: Site PI TROPOS Study Site 104
state: California
city: Torrance
country: United States
facility: TROPOS Study Site 105
state: California
city: Jacksonville
country: United States
facility: TROPOS Study Site 108
state: Florida
city: Kansas City
country: United States
facility: TROPOS Study Site 100
state: Kansas
city: Louisville
country: United States
facility: TROPOS Study Site 110
state: Kentucky
city: Boston
country: United States
facility: TROPOS Study Site 103
state: Massachusetts
city: Boston
country: United States
facility: TROPOS Study Site 109
state: Massachusetts
city: Ann Arbor
country: United States
facility: TROPOS Study Site 101
state: Michigan
city: Saint Louis
country: United States
facility: TROPOS Study Site 115
state: Missouri
city: Albuquerque
country: United States
facility: TROPOS Study Site 114
state: New Mexico
city: Cincinnati
country: United States
facility: TROPOS Study Site 113
state: Ohio
city: Charleston
country: United States
facility: TROPOS Study Site 106
state: South Carolina
city: Dallas
country: United States
facility: TROPOS Study Site 112
state: Texas
city: Houston
country: United States
facility: TROPOS Study Site 102
state: Texas
city: Melbourne
country: Australia
facility: TROPOS Study Site 805
state: Victoria
city: Auchenflower
country: Australia
facility: TROPOS Study Site 807
city: Camperdown
country: Australia
facility: TROPOS Study Site 804
city: Darlinghurst
country: Australia
facility: TROPOS Study Site 800
city: New Lambton Heights
country: Australia
facility: TROPOS Study Site 803
city: Sydney
country: Australia
facility: TROPOS Study Site 801
city: Blumenau
country: Brazil
facility: TROPOS Study Site 200
city: Porto Alegre
country: Brazil
facility: TROPOS Study Site 202
city: São Paulo
country: Brazil
facility: TROPOS Study Site 201
city: Le Kremlin-Bicêtre
country: France
facility: TROPOS Study Site 320
city: Giesen
country: Germany
facility: TROPOS Study Site 341
city: Hannover
country: Germany
facility: TROPOS Study Site 340
city: Heidelberg
country: Germany
facility: TROPOS Study Site 343
city: Homburg
country: Germany
facility: TROPOS Study Site 344
city: Leipzig
country: Germany
facility: TROPOS Study Site 342
city: Regensburg
country: Germany
facility: TROPOS Study Site 345
city: Incheon
country: Korea, Republic of
facility: TROPOS Study Site 881
city: Seoul
country: Korea, Republic of
facility: TROPOS Study Site 883
city: Seoul
country: Korea, Republic of
facility: TROPOS Study Site 882
city: Seoul
country: Korea, Republic of
facility: TROPOS Study Site 880
city: Gdańsk
country: Poland
facility: TROPOS Study Site 704
city: Kraków
country: Poland
facility: TROPOS Study Site 701
city: Otwock
country: Poland
facility: TROPOS Study Site 702
city: Poznań
country: Poland
facility: TROPOS Study Site 703
city: Poznań
country: Poland
facility: TROPOS Study Site 706
city: Łódź
country: Poland
facility: TROPOS Study Site 705
city: Almada
country: Portugal
facility: TROPOS Study Site 403
city: Coimbra
country: Portugal
facility: TROPOS Study Site 402
city: Lisboa
country: Portugal
facility: TROPOS Study Site 400
city: Porto
country: Portugal
facility: TROPOS Study Site 401
city: Barcelona
country: Spain
facility: TROPOS Study Site 412
city: Barcelona
country: Spain
facility: TROPOS Study Site 413
city: Madrid
country: Spain
facility: TROPOS Study Site 410
city: Santander
country: Spain
facility: TROPOS Study Site 411
city: Kaohsiung
country: Taiwan
facility: TROPOS Study Site 891
city: Taipei
country: Taiwan
facility: TROPOS Study Site 890
city: Glasgow
country: United Kingdom
facility: TROPOS Study Site 441
city: London
country: United Kingdom
facility: TROPOS Study Site 442
city: London
country: United Kingdom
facility: TROPOS Study Site 440
Study officials:
References: