HERMES – A research study to look at how ziltivekimab works compared to placebo in people
with heart failure and inflammation.
Scientific Title of Study
HERMES: Effects of ziltivekimab versus placebo on morbidity and mortality in patients with heart
failure with mildly reduced or preserved ejection fraction and systemic inflammation.
Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India
Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2, Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli,
Bangalore - 560045. India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Bulgaria Canada Argentina Australia Austria Belgium Bosnia and Herzegovina Brazil China Colombia Croatia Czech Republic Denmark Estonia Finland France Germany Hungary India Ireland Israel Italy Japan Latvia Lithuania Macedonia Malaysia Mexico Netherlands Norway Poland Portugal Republic of Korea Romania Serbia Singapore Slovakia Slovenia South Africa Spain Taiwan Thailand Turkey United Kingdom United States of America Greece
Amrita Institute of Medical Sciences and Research Centre
Department of Adult cardiology
5th floor, A block
Department of Adult cardiology, 5th floor, A block, Amrita Institute of Medical Sciences, AIMS- Ponekkara, Kochi, Kerala - 682041, India.
Ernakulam KERALA
9895122099
jaideepcm20533@aims.amrita.edu
Dr Jaspal Singh Arneja
Arneja Heart & Multispeciality Hospital
Department Of Cardiolog
123, Ramdaspeth, Nagpur -440010 Maharashtra,India
Nagpur MAHARASHTRA
7122448721
Jaspalarneja_200@yahoo.com
Dr Gurpreet Singh Wander
Dayanand Medical College & Hospital
Research & Development Centre, Hero DMC Heart Institute, DMC & H , Tagore Nagar, Civil Lines, Ludhiana-141001, Punjab Ludhiana PUNJAB
9815545316
drgswander@yahoo.com
Dr Rakesh Kumar Aggarwal
Deep Heart Centre, Deep Hospital
Deep Heart Centre, Deep Hospital, 478-L, Model Town, Ludhiana, Punjab - 141001 Ludhiana PUNJAB
9814215692
aggarwal.rakeshkumar@yahoo.com
Dr Anil Ranjeetmal Jain
Epic Hospital
4th floor, Clinical research department, EPIC Hospital, Rajpath Rangoli Road, Opp. Pandit Dindayal Hall, Bodakdev, Ahmedabad-380054, Gujarat, India
Ahmadabad GUJARAT
G B Pant Institute of Postgraduate Medical Education and Research
G B Pant Hospital, 1, Jawaharlal Nehru Marg, 64 Khamba, Raj Ghat - 110002 New Delhi DELHI
9718599105
drvimalmehta@yahoo.co.in
Dr Johann Christopher
Guru Nanak CARE Hospitals
Guru Nanak- CARE Hospitals - 1-4-908/7/1, Musheerabad Main Rd, near Raja Deluxe Theatre, Musheerabad, Bakaram, Kavadiguda, Hyderabad, Telangana 500020 Hyderabad TELANGANA
8143542488
johann1403@gmail.com
Dr Milind Avdhoot Gadkari
KEM Hospital
Department of Cardiology
4th floor, TBH building, CATH Lab, Sardar Moodliar road. Rasta Peeth – 411011 Pune, Maharashtra. Pune MAHARASHTRA
9822010120
gadkaris@gmail.com
Dr Monika Bhandari
King George’s Medical University
Department of Cardiology,
Administrative Block lst floor, Research cell, Uttar Pradesh 226003
Lucknow UTTAR PRADESH
8800208247
drmonikab@gmail.com
Dr V A Kothiwale
KLEs Dr. Prabhakar Kore Hospital & Medical Research Centre
Clinical Research Department
Room no. 67, Ground floor, Annex building,
Room no. 67, Clinical research department, Ground floor, Annex building, Kunnathurmedu, Chittur Road, Palakkad, Kerala 678013, India
Palakkad KERALA
9847023777
jaigopallakshmi@gmail.com
Dr Jabir Abdullakutty
Lisie Hospital
Cardilology Clinical Research room
5th floor, St. Antonys block,
Cardilology Clinical Research room, 5th floor, St. Antonys block, Lisie Hospital, P.O. Box No. 3053, Kochi, Kerala - 682018, India Ernakulam KERALA
9447011773
drjabi@yahoo.co.in
Dr Urmil Girishbhai Shah
Marengo Asia Healthcare Pvt Ltd
Plot No.67/1, Opp. Panchamrut Bungalows, Near. Shukan Mall, Off Science City Road, Sola - 380060 Ahmadabad GUJARAT
Nirmal Hospital Pvt Ltd,
Ring Road, Surat, Gujarat, India, 395002 Surat GUJARAT
9825905350
dr.pritesh@hotmail.com
Dr Krishna Mala Konda Reddy
Osmania Medical College and General Hospital
Afzalgunj - 500095 Hyderabad TELANGANA
9848015098
drkmkreddyyp@yahoo.com
Dr Raja Ramesh Nukavarapu
Ramesh Hospitals
Department of Cardiology
Clinical research room, Ground Floor,
Ramesh Hospital, Hospital road, Near ITI College Bus stop -520008, Krishna, Andhra Pradesh Krishna ANDHRA PRADESH
7094110346
nukavarapuraja@gmail.com
Dr Nirav Chandulal Bhalani
Rhythm Heart Institute
Rhythm Heart Institute, Near Siddharth Bungalows, Sama-Savli Road - 390022 Vadodara GUJARAT
8128995863
drniravbhalani@hotmail.com
Dr Ratan Lal Ranka
S.P. Medical College and A.G. Hospitals
Haldiram Moolchand Heart Hospital, SP medical college and AG hospital, PBM Hospital, Bikaner, Rajasthan 334001 Bikaner RAJASTHAN
9829217899
Drrankamdspmc@yahoo.com
Dr Suhas Prahlad Hardas
Sahyadri Super speciality Hospital
Sahyadri Super speciality Hospital, Department of Cardilogy, Plot No 30-C, Erandwane, Karve Road, Deccan GymKhana, Pune-411004, Maharashtra Pune MAHARASHTRA
9822008910
suhas_s@hotmail.com
Dr Bhupesh Rajnikant Shah
Sardar Vallabhbhai Patel Institute of Medical Sciences and Research (SVPIMSR) & NHL Medical College
Department of Cardiology
1st floor, Department of Cardiology, SVB Hospital, Ellis bridge, Ahmedabad- 380006 Ahmadabad GUJARAT
7940192444
shahbhupesh@hotmail.com
Dr Tanuj Bhatia
Shri Mahant Indiresh Hospital
Research Room, 4th Floor, South BlockKargi - Patel Nagar Bypass, Industrial Area, Govt.Industrial Estate, Patel Nagar - 248001 Dehradun UTTARANCHAL
9936618283
tanujbhatia21@rediffmail.com
Dr Mahesh Fulwani
Shrikrishna Hrudayalaya and Critical Care Centre
Shrikrishna Hrudayalaya and Critical Care Centre, Tikekar Road, Congress Nagar Square, Dhantoli, Nagpur - 440012 Nagpur MAHARASHTRA
7122444434
drmaheshfulwani@gmail.com
Dr Srihari Barama
Siddhartha Medical College & Government General Hospital
Ring Road, Gunadala, Vijaywada, ,520008, India Krishna ANDHRA PRADESH
7799851491
srihari7399@gmail.com
Dr Jitendra Pal Singh Sawhney
Sir Ganga Ram Hospital
Clinical Research Room
2nd Floor, ICICI Bank Building
In Front of SGRH Main Building, Sir Ganga Ram Hospital, Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi – 110060 New Delhi DELHI
9810059773
jpssawhney@yahoo.com
Dr Chandra Bhan Meena
SMS Hospital
Department of cardiology,2nd floor, Bangar Building, JLN Marg - 302004 Jaipur RAJASTHAN
9414250934
drcbmsms@gmail.com
Dr Satvic C Manjunath
Sri Jayadeva Institute of Cardiovascular Sciences & Research
Sri Jayadeva Institute of Cardiovascular Sciences & Researc,
Jayanagar 9th Block, Bannerghatta Road, Bengaluru, Karnataka, 560069
Bangalore KARNATAKA
9880524279
satvic.jayadeva@gmail.com
Dr Ajit Mullasari Sankardas
The Madras Medical Mission Hospital
4A, Dr. Jayalalitha Nagar, Mogappair, Chennai,
TAMIL NADU-600037
Chennai TAMIL NADU
9841271361
icvddoctors@mmm.org.in
Dr Sandeep Bansal
Vardhaman Mahavir Medical College & Safdarjung Hospital
Room Number 719, 7th Floor, Super Speciality Block SSB VMMC & Safdarjung Hospital, New Delhi-110029 New Delhi DELHI
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 per L at screening visit 1
Disease specific cardiovascular
4 At least one of the following
NT proBNP greater than and equal to 300 pg per mL at screening visit 1 for patients without ongoing atrial fibrillation or flutter If ongoing atrial fibrillation or flutter at screening visit 1 NTproBNP must be greater than or equal to 600 pg per mL Note that the screening ECG must be obtained the same day as sampling for NT proBNP
HF hospitalisation or urgent or 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 NTproBNP greater than or equal to 200 pg per mL at screening Visit 1 for patients without ongoing atrial fibrillation or flutter If ongoing atrial fibrillation or flutter at screening visit 1 NTproBNP must be greater than or equal to 600 pg per mL
5 Diagnosis of heart failure NYHA Class two to four
6.LVEF greater than 40 percentage 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 example 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
LA volume index greater than 34 mL per m2
LA diameter greater than or equal to 3 point 8 cm
LA length greater than or equal to 5 point 0 cm
LA area greater than or equal to 20 cm2
LA volume greater than or equal to 55 mL
Intraventricular septal thickness greater than or equal to 1 point 1 cm
Posterior wall thickness greater than or equal to 1 point 1 cm
LV mass index greater than or equal to 115 g per m2 in men or greater than or equal to 95 g per m2 in women
E per mean septal and lateral greater than or equal to 10
e mean septal and lateral leass than 9 cm per s
8 No heart failure hospitalisations or urgent heart failure visits between screening visit 1 and
randomisation visit 2
ExclusionCriteria
Details
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 point 4 point 2
4 Participation which means 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 or circumstance, which in the investigators opinion might jeopardise participants safety or compliance with the protocol
7 Inadequate standard of care treatment which in the investigators 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 less than 2 multiplied by 109 per L at screening visit 1
10 Platelet count less than 20 multiplied by 109 per L at screening visit 1
11 Alanine aminotransferase as ALT or aspartate aminotransferase as AST greater than 2 point 5 multiplied by 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 point 2 point 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 greater than or equal to 180 mmHg at screening visit 1 If the systolic blood pressure is 160 to179 mmHg the patient should be receiving greater than or equal to 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 revascularisation known during the screening period visit 1 Note planned coronary angiogram is not exclusionary
17 Planned cardiac device or atrial flutter or atrial fibrillation ablation procedure known during the
screening period visit 1
18 Major cardiac surgical non cardiac surgical or major endoscopic procedure thoracoscopic or laparoscopic within the past 60 days prior to randomisation visit 2 or any major surgical procedure planned at the time of randomisation visit 2
19 Left Ventricular Assist Device LVAD implantation or heart transplantation
20 Heart failure due to infiltrative cardiomyopathy example sarcoid amyloid arrhythmogenic right ventricular cardiomyopathy Takutsubo cardiomyopathy genetic hypertrophic cardiomyopathy or obstructive cardiomyopathy active myocarditis constrictive pericarditis cardiac tamponade uncorrected more than moderate primary valve disease
21 Primary pulmonary hypertension chronic pulmonary embolism severe pulmonary disease including COPD
22 Any other condition judged by the investigator that could account for heart failure symptoms and signs example anaemia hypothyroidism
Medical conditions infections or immunosuppression
23 Clinical evidence of or suspicion of active infection at the discretion of the investigator
24 History of recurrent serious infections leading to hospitalisation or use of iv antibiotics in the 12 months prior to randomisation visit 2 at the discretion of the investigator
25 Diagnosis of human immunodeficiency virus HIV and not receiving a stable antiretroviral regimen at the discretion of the investigator at screening visit 1
26 History or evidence of untreated latent tuberculosis TB such as but not limited to
History of a positive TB test or chest X ray compatible with latent TB and TB treatment initiated less than 28 days prior to randomisation visit 2
Confirmed positive for latent TB at screening visit 1 see Section 8 point 2 point 7 for details and TB
treatment initiated less than 28 days prior to randomisation visit 2
Medical conditions General health and safety
27 eGFR less than 15 mL per min per 1 point 73 m2 CKD EPI10 at screening visit 1 or chronic haemodialysis or peritoneal dialysis
28 History of gastrointestinal perforation Note History of perforated appendicitis more than 5 years prior to screening visit 1 is not exclusionary
29 History of active diverticulitis in the 5 years prior to randomisation visit 2
30 History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomisation visit 2
31 Presence or history of malignant neoplasms or in situ carcinomas other than basal or squamous cell skin cancer low risk prostate cancer or in situ carcinomas of the cervix or carcinoma in situ or high grade prostatic intraepithelial neoplasia PIN within 5 years prior to screening visit 1
32 History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the study Note Patients no longer receiving immune suppressant therapy and who are in full remission following bone marrow transplant can be included in the study Prior or current medication
33 Received a live or attenuated live vaccine product within 4 weeks of study intervention administration visit 2 or expected to receive a live or attenuated-live vaccine product during the treatment period Note Not live and not attenuated live vaccines are not exclusionary For guidance refer to Appendix 10 Section 10 point 10
34 Use of preventive systemic antibiotics systemic antivirals or systemic antifungals at screening visit 1 Note Systemic is defined as oral or iv administered drugs that are absorbed into the circulation Antibiotics used to treat latent TB are exempted
35 Use of systemic immunosuppressive drugs both small molecules and biologics or disease modifying anti rheumatic drugs DMARDs including both biologic DMARDs like anti TNFalpha and conventional DMARDs like methotrexate at screening visit 1 or anticipated chronic use of such drugs any time during the study Note Use of otic ophthalmic, inhaled, and topical
corticosteroids or local corticosteroid injections are not exclusionary
36 Use of anti IL 6 products at screening visit 1 or anticipated use of such drugs any time during
the study
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once-monthly
versus placebo, both added to standard
of care, in reducing the risk of CV
death and HF events in participants
with HFmrEF or HFpEF and systemic
inflammation.
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once-monthly
versus placebo, both added to standard
of care, in reducing the risk of
expanded composite HF endpoint in
participants with HFmrEF or HFpEF
and systemic inflammation.
From randomisation
(month 0) to end of
study (up to 48 months)
Number of CV deaths, HF
hospitalisations or urgent HF visits
(first and recurrent)
From randomisation
(month 0) to end of
study (up to 48 months)
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once-monthly
versus placebo, both added to standard
of care, in improving overall clinical benefits, in
participants with HFmrEF or HFpEF
and systemic inflammation.
From randomisation
(month 0) to end of
study (up to 48 months)
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once monthly
versus placebo both added to standard
of care In reducing the risk of atrial fibrillation (AF) events in
participants with HFmrEF or HFpEF
and systemic inflammation
From randomisation
(month 0) to end of
study (up to 48 months)
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once monthly
versus placebo both added to standard
of care in improving the health status of participants in
participants with HFmrEF or HFpEF
and systemic inflammation
From randomisation
(month 0) to 12 months
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once monthly
versus placebo both added to standard
of care on progression of CKD in participants with HFmrEF or HFpEF
and systemic inflammation
From randomisation
(month 0) to end of
study (up to 48 months)
To compare the effects of
ziltivekimab 15 mg s.c. oncemonthly
versus placebo, both
added to standard of care in
participants with HFmrEF or
HFpEF & systemic inflammation
on risk of severe infections
From randomisation
(month 0) to end of
study (up to 48 months)
To compare the effects of
ziltivekimab versus placebo on
biomarkers of inflammation HF
and anaemia in participants with
HFmrEF or HFpEF & systemic
inflammation
From randomisation
(month 0) to 12 months
To demonstrate the superiority of
ziltivekimab 15 mg s.c. once monthly
versus placebo both added to standard
of care in reducing the risk of HF events in participants with HFmrEF or HFpEF
and systemic inflammation
From randomisation
(month 0) to end of
study (up to 48 months)
Total Sample Size="5600" Sample Size from India="350" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study will be do to see if ziltivekimab can be used to treat people with heart failure and inflamation. Participants will either get ziltivekimab or placebo.This is an interventional, randomised, parallel-group, double-blind, placebo-controlled, multicentre, multi-national cardiovascular outcomes trial (CVOT) designed to evaluate the effects of ziltivekimab 15 mg versus placebo (randomised 1:1), both administered s.c. once-monthly and added to standard of care, on morbidity and mortality of participants with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) or HF with preserved ejection fraction (HFpEF) and systemic inflammation.
The study consists of 3 periods: a screening period (up to 5 weeks), a treatment period and a 3- month follow-up period after the end of treatment visit. Eligible participants will be randomly assigned to study intervention prior to initiation of the treatment period. This study is expected to last for upto four years. Participants will have upto 20 clinic visits. Participants will have to use a study app in their phone to record and share information about all their injections of their study medicine and their questionaires.