HERMES – A research study to look at how ziltivekimab works compared to placebo in peoplewith heart failure and inflammation.
- Conditions
- Health Condition 1: I503- Diastolic (congestive) heart failure
- Registration Number
- CTRI/2023/06/053508
- Lead Sponsor
- ovo Nordisk India Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
All inclusion criteria are based on the participants’ medical records, except for inclusion criteria #3
(hs-CRP at central laboratory), #4 (NT-proBNP at central laboratory, and ECG assessed at
screening) and #5 (NYHA class) assessed at screening (visit 1).
Local requirements may apply. China, Czech Republic, France, Germany, Hungary, Lithuania,
Netherlands, Portugal, Singapore, South Korea, Spain, Taiwan: see country/region-specific
requirements (Appendix 11, Section 10.11).
Participants are eligible to be included in the study only if all the following criteria apply:
General
1. Informed consent obtained before any study-related activities. Study-related activities are any
procedures that are carried out as part of the study, including activities to determine suitability
for the study.
2. Age 18 years or above at the time of signing the informed consent.
3. Serum hs-CRP ?2 mg/L at screening (visit 1).a
Disease specific - cardiovascular
4. At least one of the followinga:
a. NT-proBNP = 300 pg/mL at screening (Visit 1) for patients without ongoing atrial
fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP
must be = 600 pg/mL.
b. HF hospitalisation or urgent/unplanned visit with a primary diagnosis of
decompensated heart failure which required intravenous loop diuretic treatment,
within the last 9 months prior to screening (visit 1) in combination with NT-proBNP
= 200 pg/mL at screening (Visit 1) for patients without ongoing atrial
fibrillation/flutter. If ongoing atrial fibrillation/flutter at screening (visit 1), NTproBNP
must be = 600 pg/mL.
5. Diagnosis of heart failure (NYHA Class II-IV).
6. LVEF > 40% documented by echocardiography within 12 months prior to or at screening
(visit 1). The LVEF must be documented in medical records and the most recent measurement
must be used to determine eligibility with no interim event signalling potential deterioration in
ejection fraction (e.g., MI or HF hospitalisation).
7. Structural heart disease and/or functional heart disease documented by echocardiography within
12 months prior to or at screening (visit 1) showing at least one of the following:
o LA volume index > 34 mL/m2.
o LA diameter = 3.8 cm.
o LA length = 5.0 cm.
o LA area = 20 cm2.
o LA volume = 55 mL.
o Intraventricular septal thickness =1.1 cm.
o Posterior wall thickness =1.1 cm.
o LV mass index =115 g ? m2 in men or = 95 g ? m2 in women.
o E/e’ (mean septal and lateral) = 10.
o e’ (mean septal and lateral) < 9 cm/s.
8. No heart failure hospitalisations or urgent heart failure visits between screening (visit 1) and
randomisation (visit 2).
a Patients participating in the prevalence study (NN6018-7527) may be enrolled based on the hs-
CRP and/or NT-proBNP (requiring corresponding ECG from the same date) results obtained in the
study, if no more than 90 days old.
Local requirements may apply. Germany, South Korea: see country/region-specific requirements
(Appendix 11, Section 10.11).
All exclusion criteria are based on the participants’ medical records, except for exclusion criterion
#3 (urine pregnancy test), criteria #9 to #12 and #27 (central laboratory tests), criteria #26 (central
laboratory tests, if applicable), criterion #14 (blood pressure) and criterion #15 (ECG).
Local requirements may apply. Argentina, Austria, Belgium, Brazil, China, Czech Republic,
Denmark, Finland, France, Germany, Greece, Ireland, Italy, Latvia, Lithuania, Norway, Poland,
Portugal, Romania, South Korea, Spain, Thailand, UK: see country/region-specific requirements
(Appendix 11, Section 10.11).
Participants are excluded from the study if any of the following criteria apply:
General
1. Known or suspected hypersensitivity to study intervention or related products.
2. Previous randomisation in this study.
3. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing
potential and not using a highly effective contraceptive method, as defined in Appendix 4
(Section 10.4.2).
4. Participation (i.e., signed informed consent) in any other interventional clinical study of an
approved or non-approved investigational medicinal product within 30 days prior to screening
(visit 1).
5. Participation in any clinical study of an approved or non-approved device for the treatment of
heart failure within 30 days prior to screening (visit 1).
6. Any disorder, which in the investigator’s opinion might jeopardise participant’s safety or
compliance with the protocol.
7. Inadequate standard of care treatment which in the investigator’s opinion makes participation in
the study inappropriate.
8. Unstable medical therapy for heart failure (including dose of diuretics) within 14 days prior to
screening visit (visit 1) (at the discretion of the investigator).
Laboratory values
9. Absolute neutrophil count <2×109/L at screening (visit 1).
10. Platelet count <120×109/L at screening (visit 1).
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of
normal at screening (visit 1).
12. Active hepatitis C (positive anti-HCV and detectable HCV RNA) or hepatitis B (positive
HBsAg and/or positive anti-HBc with detectable HBV DNA) at screening (visit 1). (Note:
Participants with positive anti-HBc and undetectable HBV DNA can be enrolled; see
Section 8.2.8 for details).
Medical conditions – cardiovascular
13. Myocardial infarction, stroke, unstable angina pectoris, transient ischaemic attack, or heart
failure hospitalisation within 30 days prior to screening (visit 1).
14. Systolic blood pressure =180 mmHg at screening (visit 1). If the systolic blood pressure is 160-
179 mmHg, the patient should be receiving =3 antihypertensive drugs. (Note: Potential
participants may be retested for this criterion within the visit window and without rescreening,
at the discretion of the investigator).
15. Heart rate above 110 or below 40 beats per minute as evaluated on the ECG performed at
screening (visit 1) (Note: Potential participants may be retested for this criterion within the visit
window and without rescreening, at the discretion of the investigator).
16. Planned coronary, carotid or peripheral artery revascu
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To demonstrate the superiority of <br/ ><br>ziltivekimab 15 mg s.c. once-monthly <br/ ><br>versus placebo, both added to standard <br/ ><br>of care, in reducing the risk of CV <br/ ><br>death and HF events in participants <br/ ><br>with HFmrEF or HFpEF and systemic <br/ ><br>inflammation.Timepoint: at 48 Months
- Secondary Outcome Measures
Name Time Method umber of CV deaths, HF <br/ ><br>hospitalisations or urgent HF visits <br/ ><br>(first and recurrent)Timepoint: From randomisation <br/ ><br>(month 0) to end of <br/ ><br>study (up to 48 months);To demonstrate the superiority of <br/ ><br>ziltivekimab 15 mg s.c. once-monthly <br/ ><br>versus placebo, both added to standard <br/ ><br>of care, in reducing the risk of death in <br/ ><br>participants with HFmrEF or HFpEF <br/ ><br>and systemic inflammation.Timepoint: From randomisation <br/ ><br>(month 0) to end of <br/ ><br>study (up to 48 months);To demonstrate the superiority of <br/ ><br>ziltivekimab 15 mg s.c. once-monthly <br/ ><br>versus placebo, both added to standard <br/ ><br>of care, in reducing the risk of <br/ ><br>expanded composite HF endpoint in <br/ ><br>participants with HFmrEF or HFpEF <br/ ><br>and systemic inflammation.Timepoint: From randomisation <br/ ><br>(month 0) to end of <br/ ><br>study (up to 48 months)