Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001290684
Ethics application status
Approved
Date submitted
27/10/2023
Date registered
11/12/2023
Date last updated
14/07/2024
Date data sharing statement initially provided
11/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2, Open-label, Single-arm Study to Evaluate the Tolerability, Safety, and Pharmacodynamic Effects of KER-012 in Participants with Chronic Heart Failure.
Scientific title
A Phase 2, Open-label, Single-arm Study to Evaluate the Tolerability, Safety, and Pharmacodynamic Effects of KER-012 in Participants with Chronic Heart Failure.
Secondary ID [1] 309865 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Heart Failure 330304 0
Condition category
Condition code
Cardiovascular 327163 327163 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in this study will be adults with Chronic Heart Failure.
Cohort 1: Participants with Heart Failure with preserved Ejection Fraction (HFpEF)
Cohort 2: Participants with Heart Failure with reduced Ejection Fraction (HFrEF)
Participants will be administered 4.5 mg/kg of KER-012 by the Investigator or registered nurse subcutaneously every 4 weeks over a 20 week period. Adherence will be monitored by the vials used.
Intervention code [1] 326372 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 335157 0
Tolerability and safety will be assessed by incidence of treatment emergent adverse events (TEAEs), treatment-related TEAEs and discontinuations due to TEAEs, including but not limited to injection site reactions, assessed by investigator and patient self-reporting.
Timepoint [1] 335157 0
Screening (time consent form signed and visits required for screening), week 0, 2, 4, 8, 12, 16, 20, 24 (End of Treatment visit) and 28 (end of study visit). Patients to contact site staff in between study visits to self-report adverse events as required.
Primary outcome [2] 335160 0
Tolerability and safety will be assessed by changes from baseline in clinical laboratory values by laboratory tests, vital signs measured by qualified site staff and heart health by electrocardiogram.
Timepoint [2] 335160 0
Screening visit, week 0, 2, 4 and every 4 weeks thereafter until end of study safety visit (week 28).
Primary outcome [3] 335163 0
Tolerability and safety will be assessed by incidence of anti-drug antibody (ADA) measured using an enzyme-linked immunosorbent assay (ELISA).
Timepoint [3] 335163 0
Week 0, 2, 4 and every 4 weeks thereafter, collected pre-dose on dosing days, until end of study safety visit (week 28) or up to 12 months after last dose if participants have positive ADA reading at end of study safety visit.
Secondary outcome [1] 423326 0
Impact on N-terminal pro b-type natriuretic peptide (NT-proBNP) levels assessed by a blood test.
Timepoint [1] 423326 0
Screening visit, week 0, 2, 4 and every 4 weeks thereafter until end of study safety visit (week 28).
Secondary outcome [2] 423347 0
Pharmacokinetic profile of KER-012 assessed using blood tests. Pharmacokinetic outcomes include population PK (popPK).
Timepoint [2] 423347 0
Week 0, 2, 4 and every 4 weeks thereafter until the week 24 end of treatment visit.
Secondary outcome [3] 423348 0
Pharmacodynamic response of KER-012 assessed using blood tests.
Timepoint [3] 423348 0
Screening visit, week 0, 2, 4 and every 4 weeks thereafter until end of study safety visit (week 28).

Eligibility
Key inclusion criteria
1. Adult participants greater than or equal to 45 to less than or equal to 80 years of age with a diagnosis of either Heart Failure (HF) patients with preserved Ejection Fraction (HFpEF) (Left Ventricular Ejection Fraction (LVEF) greater than or equal to 50%) or Heart Failure patients with reduced Ejection Fraction (HFrEF) (LVEF less than or equal to 40%) with elevated N-terminal pro b-type natriuretic peptide (NT-proBNP) (> 150 pg/mL) despite appropriate and stable HF-directed medical regimen.
a. Stable therapy is defined as no change in dose/regimen for at least 30 days prior to Baseline and would be expected to be maintained for the duration of study.
b. Participants with HFpEF with defined greater than or equal to Grade 2 diastolic dysfunction.
c. Participants with HFpEF with defined body mass index (BMI) of greater than or equal to 20 and less than or equal to 40 kg/m squared.

2. Stable New York Heart Association Functional Class (NYHA FC) II to IV symptoms for 30 days prior to enrollment as assessed by the investigator at Screening.

3. If participant is taking concomitant medications that may affect clinical HF symptoms (i.e., diuretics, vasodilators, cardiostimulatory or inotropic, cardioinhibitory drugs), the participant must be on a stable dose for at least 30 days prior to Baseline, and the dose would be expected to be maintained during the study.
Minimum age
45 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. BMI > 40 kg/m squared.

2. HFpEF and HFrEF cohorts:

- HFpEF Cohort: Cardiovascular comorbidities, which include any of the following:
a. Acute coronary syndrome, acute coronary artery bypass graft, acute percutaneous coronary intervention, or new left bundle branch block within the last 90 days of Visit 1.
b. Uncontrolled systemic hypertension as evidenced by seated systolic blood pressure (BP) > 160 mmHg or seated diastolic BP > 100 mmHg at Screening.
c. Systemic hypotension as evidenced by a sitting Systolic BP < 90 mmHg at Screening or sitting diastolic blood pressure < 50 mmHg at Screening.
d. QT interval corrected by Fridericia (QTcF) recorded on ECG at Screening as follows:
i. Male participants with QTcF > 450 msec.
ii. Female participants with QTcF > 470 msec.
Note: Participants with intraventricular conduction delay defined as QRS > 110 msec will be excluded if QTcF is > 500 msec (both male and female).
e. History of known pericardial constriction, sarcoidosis, or amyloid cardiomyopathy.

- HFrEF cohort: Cardiovascular comorbidities, which include any of the following:
a. Acute coronary syndrome, acute coronary artery bypass graft, acute percutaneous coronary intervention, or new left bundle branch block within the last 90 days of Visit 1.
b. Uncontrolled heart rate (> 100 bpm) from atrial fibrillation or atrial flutter.
c. History of serious life-threatening or haemodynamically significant arrhythmia.
d. Resting heart rate of < 45 bpm or > 115 bpm.
e. Acutely decompensated HF that required hospitalisation within 30 days of Visit 1.
f. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mmHg or seated diastolic BP > 100 mmHg at Screening after a period of rest.
g. Systemic hypotension as evidenced by a sitting Systolic BP < 90 mmHg at Screening or sitting diastolic blood pressure < 50 mmHg at Screening.
h. QT interval corrected by Fridericia (QTcF) recorded on ECG at Screening as follows:
i. Male participants with QTcF > 450 msec.
ii. Female participants with QTcF > 470 msec.
Note: Participants with intraventricular conduction delay defined as QRS > 110 msec will be excluded if QTcF is > 500 msec (both male and female) unless a ventricular conduction defect (right bundle branch block; left bundle branch block; or interventricular conduction delay) is present at baseline and not new within 90 days of Visit 1.
iii. Personal or family history of Brugada syndrome.
iv. Personal or family history of long QT syndrome unless the participant's ECG shows a normal QTc.
i. Personal history of sudden cardiac arrest or family history of unexplained sudden cardiac death or arrest.
j. Stroke within 90 days of Visit 1.
k. Any history of greater than mild mitral or aortic regurgitation valvular disease or greater than mild aortic or mitral stenosis. Severe tricuspid regurgitation may be included unless it is due to primary valvular disease, e.g., from endocarditis, carcinoid, or mechanical destruction.
l. Anticipated cardiac valve replacement or repair (mechanical or biomechanical) during the study period.
m. History of or anticipated heart transplant or ventricular assist device implantation.
n. Implantation of pacemaker or implantable cardioverter defibrillator placement within 30 days of Screening.

3. Known history of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Class A to C).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
The sample size minimum of 6 and up to 8 participants for each cohort is based on clinical considerations.
Results of each cohort (HFpEF and HFrEF) will be analysed descriptively. No formal statistical hypothesis will be tested in this study. In general, data will be summarised by cohort and/or pooled when appropriate, using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages.
Baseline is defined as the last available, valid, non-missing assessment on or prior to the first dose of KER-012.
Statistical methodology will be included in the Statistical Analysis Plan, which will be finalised prior to any database lock.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Other reasons/comments
Other reasons
Sponsor portfolio management activities.
Date of first participant enrolment
Anticipated
20/06/2024
Actual
Date of last participant enrolment
Anticipated
14/11/2024
Actual
Date of last data collection
Anticipated
14/05/2025
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC

Funding & Sponsors
Funding source category [1] 314047 0
Commercial sector/Industry
Name [1] 314047 0
Keros Therapeutics, Inc.
Country [1] 314047 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Keros Therapeutics, Inc.
Address
1050 Waltham Street, Suite 302, Lexington, MA 02421
Country
United States of America
Secondary sponsor category [1] 315948 0
Commercial sector/Industry
Name [1] 315948 0
Advanced Clinical Pty Ltd
Address [1] 315948 0
60 Martin Place, Level 1, Sydney, NSW, 2000
Country [1] 315948 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313184 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 313184 0
Ethics committee country [1] 313184 0
Australia
Date submitted for ethics approval [1] 313184 0
02/09/2023
Approval date [1] 313184 0
16/10/2023
Ethics approval number [1] 313184 0

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

Contacts
Principal investigator
Name 127270 0
A/Prof Piyush Srivastava
Address 127270 0
Advara HeartCare, Suite 8, Churchill Consulting Suites, Blanton Drive, Mulgrave VIC 3170
Country 127270 0
Australia
Phone 127270 0
+61 03 9701 1732
Fax 127270 0
Email 127270 0
[email protected]
Contact person for public queries
Name 127271 0
Justin Frantz
Address 127271 0
Keros Therapeutics, Inc. 1050 Waltham St, Suite 302, Lexington, MA
Country 127271 0
United States of America
Phone 127271 0
+1 617 221 6042
Fax 127271 0
Email 127271 0
[email protected]
Contact person for scientific queries
Name 127272 0
Kate Steiner
Address 127272 0
Keros Therapeutics, Inc. 1050 Waltham St, Suite 302, Lexington, MA
Country 127272 0
United States of America
Phone 127272 0
+1 617 448 0363
Fax 127272 0
Email 127272 0
[email protected]

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


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.