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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05975905




Registration number
NCT05975905
Ethics application status
Date submitted
13/07/2023
Date registered
4/08/2023

Titles & IDs
Public 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).
Scientific 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)
Secondary ID [1] 0 0
KER-012-A201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Dose A KER-012
Treatment: Other - Dose B KER-012
Treatment: Other - Dose C KER-012
Treatment: Other - Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks

Experimental: Arm 1 (N=20) - 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

Experimental: Arm 2 (N=20) - KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks

Experimental: Arm 3 (N=20) - KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks

Placebo comparator: Arm 4 (N=30) - Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks


Treatment: Other: Dose A KER-012
Dose A KER-012 (Q4W);

Treatment: Other: Dose B KER-012
Dose B KER-012 (Q4W);

Treatment: Other: Dose C KER-012
Dose C KER-012 (Q4W);

Treatment: Other: 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)
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in PVR (Pulmonary Vascular Resistance)
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [1] 0 0
Change from Baseline in the 6MWD
Timepoint [1] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [2] 0 0
Incidence of treatment-emergent adverse events (TEAEs)
Timepoint [2] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [3] 0 0
Number of treatment-related TEAEs
Timepoint [3] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [4] 0 0
Number of discontinuations due to TEAEs
Timepoint [4] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [5] 0 0
Change from baseline in Systolic and Diastolic Blood Pressure
Timepoint [5] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [6] 0 0
Change from baseline in QTcF intervals
Timepoint [6] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [7] 0 0
Incidence of Antidrug Antibodies (ADA)
Timepoint [7] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [8] 0 0
Evaluate the changes from baseline in the concentration of the PAH biomarker, NT-proBNP in blood samples
Timepoint [8] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [9] 0 0
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- mPAP
Timepoint [9] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [10] 0 0
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- CO
Timepoint [10] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [11] 0 0
Evaluate the effect of KER-012 on pulmonary hemodynamics compared to Placebo in participants on background PAH therapy- PAWP
Timepoint [11] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [12] 0 0
Evaluate improvement in functional assessment of KER-012 compared to Placebo in participants on background PAH therapy
Timepoint [12] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [13] 0 0
Number of participants who experienced events indicative of clinical worsening of pulmonary arterial hypertension (PAH)
Timepoint [13] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)
Secondary outcome [14] 0 0
Population PK predicted maximum concentration (Cmax) of KER-012
Timepoint [14] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [15] 0 0
Population PK predicted Area under concentration curve (AUC) of KER-012
Timepoint [15] 0 0
Through week 24 (primary treatment period) and Through week 96 (extension period)
Secondary outcome [16] 0 0
Evaluate improvement in risk stratifications of KER-012 in participants on background PAH therapy
Timepoint [16] 0 0
Up to week 24 (primary treatment period) and up to Week 96 (extension period)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2027
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
TROPOS Study Site 805 - Melbourne
Recruitment hospital [2] 0 0
TROPOS Study Site 804 - Camperdown
Recruitment hospital [3] 0 0
TROPOS Study Site 800 - Darlinghurst
Recruitment hospital [4] 0 0
TROPOS Study Site 803 - New Lambton Heights
Recruitment hospital [5] 0 0
TROPOS Study Site 801 - Sydney
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [5] 0 0
2095 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Mexico
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Brazil
State/province [13] 0 0
Blumenau
Country [14] 0 0
Brazil
State/province [14] 0 0
Porto Alegre
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Germany
State/province [16] 0 0
Giesen
Country [17] 0 0
Germany
State/province [17] 0 0
Hannover
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Germany
State/province [19] 0 0
Homburg
Country [20] 0 0
Germany
State/province [20] 0 0
Leipzig
Country [21] 0 0
Germany
State/province [21] 0 0
Regensburg
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Incheon
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Poland
State/province [24] 0 0
Gdansk
Country [25] 0 0
Poland
State/province [25] 0 0
Kraków
Country [26] 0 0
Poland
State/province [26] 0 0
Otwock
Country [27] 0 0
Poland
State/province [27] 0 0
Poznan
Country [28] 0 0
Poland
State/province [28] 0 0
Lódz
Country [29] 0 0
Portugal
State/province [29] 0 0
Almada
Country [30] 0 0
Portugal
State/province [30] 0 0
Coimbra
Country [31] 0 0
Portugal
State/province [31] 0 0
Lisboa
Country [32] 0 0
Portugal
State/province [32] 0 0
Porto
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Santander
Country [36] 0 0
Taiwan
State/province [36] 0 0
Kaohsiung
Country [37] 0 0
Taiwan
State/province [37] 0 0
Taipei
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Glasgow
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Keros Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Keros Therapeutics, Inc.
Address 0 0
Country 0 0
Phone 0 0
+1 617 3146297
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05975905