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CTRI Number  CTRI/2021/03/032022 [Registered on: 16/03/2021] Trial Registered Prospectively
Last Modified On: 24/02/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Research study on whether semaglutide works in people with non-alcoholic steatohepatitis (NASH)  
Scientific Title of Study   The effect of semaglutide in subjects with non-cirrhotic non-alcoholic steatohepatitis  
Trial Acronym  ESSENCE 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
NN9931-4553 Version 15.0 Dated 12 Jan 2024  Protocol Number 
NN9931-4553 Version 11.0 Dated 11 Feb 2022  Protocol Number 
NN9931-4553 Version 16.0 Dated 16 May 2024  Protocol Number 
NN9931-4553 Version 17.0 Dated 31 Jan 2025  Protocol Number 
NN9931-4553 Version 9.0 Dated 24 June 2021  Protocol Number 
NN9931-4553_Version 12.0 Dated 28 Oct 2022  Protocol Number 
NN9931-4553_Version 14.0 dated 25 September 2023  Protocol Number 
UTN no: U1111-1244-3678  UTN 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Vijay Parthasarathy 
Designation  Director, CDC India 
Affiliation  Novo Nordisk India private Ltd 
Address  Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India
Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India
Bangalore
KARNATAKA
560045
India 
Phone  8040303200  
Fax  08041123518  
Email  VJYP@novonordisk.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Vijay Parthasarathy 
Designation  Director, CDC India 
Affiliation  Novo Nordisk India private Ltd 
Address  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
Bangalore
KARNATAKA
560045
India 
Phone  8040303200  
Fax  08041123518  
Email  VJYP@novonordisk.com  
 
Source of Monetary or Material Support
Modification(s)  
Novo Nordisk India Private Limited, Nxt Tower - 2, Floor 1 & 2 Embassy Manyata Business Park, Nagavara Village, Kasaba Hobli, Bangalore - 560045. India Tel No.: 080-40303200  
 
Primary Sponsor
Modification(s)  
Name  Novo Nordisk  
Address  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     Argentina
Australia
Austria
Belgium
Brazil
Bulgaria
Canada
China
Croatia
Czech Republic
Denmark
France
Germany
Greece
India
Ireland
Israel
Italy
Japan
Malaysia
Mexico
Netherlands
Norway
Poland
Romania
Russian Federation
Serbia
Slovakia
South Africa
Spain
Switzerland
Taiwan
Turkey
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 18  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Shalimar  All India Institute Of Medical Sciences  All India Institute Of Medical Sciences,Room No.124, First Floor,Human Nutrition unit,Old OT Block, Ansari Nagar, new delhi,110029
New Delhi
DELHI 
9968405815

drshalimar@yahoo.com 
Dr Parshottam Koradia  BAPS Pramukh Swami Hospital  Shri Pramukh Swami Maharaj Marg,, Adajan Char Rasta, Adajan, Surat, Gujarat 395009
Surat
GUJARAT 
9825312027

purushottam_koradia@yahoo.co.in 
Dr Vandana Midha  Dayanand Medical College and Hospital  Dayanand Medical College and Hospital, Ludhiana, 141001
Ludhiana
PUNJAB 
919815528289

vandana_midha2@yahoo.co.in 
Dr Kiran Pal Singh  Fortis hospital  Fortis hospital, endocrinology fortis hospital Phase 8 sector 62mohali pb mohali,160062,Punjab,India
Fatehgarh Sahib
PUNJAB 
09815311711

drkp1292@gmail.com 
Dr Alisha Chaubal  Gleneagles Hospital, Super - Specialty and transplant centre Mumbai  Gleneagles Hospital-super specialty and transplant centre,35, Dr. E. Borges road, Hospital avenue, Opp. Dr shirodkar high school, Parel,400012,Maharashtra, Indi
Mumbai
MAHARASHTRA 
9820144338

alishachaubal@gmail.com 
Dr Shiv Kumar Sarin  Institute Of Liver And Biliary Sciences  Institute Of Liver And Biliary Sciences , D-1, Vasant Kunj, New Delhi 110070,India
New Delhi
DELHI 
9540947000

sksarin@ilbs.in 
Dr B V Tantry  Kasturba Medical College Hospital   Kasturba Medical College Hospital Dr.B.R.Ambedker Circle, Mangalore-575001, Karnataka
Dakshina Kannada
KARNATAKA 
09845789100

tantrybv@gmail.com 
Dr Paturi Vishnupriya Rao  Kumudini Devi Diabetes Research Center  Diabetes Research Center First Floor 6-3-349/178,Hindi Nagar Colony, Behind Panjagutta Saibaba Temple, Hyderabad, Telangana - 500082 India -500072, Telangana, India.
Hyderabad
TELANGANA 
914026661331

raopaturi@gmail.com 
Dr S K Gupta  M.V. Hospital  M.V. Hospital, lucknow 314/30, Mirza Mandi,,Chowk, Lucknow- Uttar Pradesh Lucknow,Uttar pradesh - 226003, India
Lucknow
UTTAR PRADESH 
9336077839

sandeepkumar.gupta@rediffmail.com 
Dr Narendra Choudhary  Medanta The Medicity Hospital  Sec-38, Gurgaon, Haryana - 122 001, India
Gurgaon
HARYANA 
8130188600

Narendra.Choudhary@Medanta.org 
Dr Shrikant Mukewar  Midas multispeciality hospital pvt.ltd  Midas Hospital, 392, Behind Empress Palace, Opp Singh Saab Dhaba, Wardha Road, Parsodi, Nagpur-441108.
Nagpur
MAHARASHTRA 
7720033280

shrikant_mukewar@yahoo.com 
Dr Rakesh Kumar Sahay  Osmania General Hospital  Osmania General Hospital, Hyderabad, Telangana - 500012
Hyderabad
TELANGANA 
9849597507

sahayrk@gmail.com 
Dr Ajay Duseja  Post Graduate Institute of Medical Education and Research  Post Graduate Institute of Medical Education and Research Nehru hospital, 2nd floor, d Block, Faculty offices,room no.-5, sector- 12 , PGIMER,chandigarh,160012
Chandigarh
CHANDIGARH 
9417007416

ajayduseja@yahoo.co.in 
Dr Mukesh Jain  S.M.S Hospital  S.M.S Hospital,JLN marg, jaipur,302004, Rajasthan, India
Jaipur
RAJASTHAN 
9414323607

drmukeshjaingastro@gmail.com 
Dr Mukesh Kalla  S.R. Kalla memorial gastro and general hospital  S.R. Kalla memorial gastro and general hospital 78-79 dhuleshwar garden behind hsbc bank Sp marg c-scheme jaipur-302001 rajasthan india
Jaipur
RAJASTHAN 
9829050622

drmkalla@rediffmail.com 
Dr Akash Shukla  Seth G.S.Medical College and K.E.M Hospital  Seth G.S.Medical College and K.E.M Hospital, Department of Gastroenterology,Ward 32A,9th floor,M.S.Building,, Parel,Mumbai 400 012
Mumbai
MAHARASHTRA 
9869256376

drakashshukla@yahoo.com 
Dr Rajiv Mehta  Surat institute of Digestive Sciences  SIDS Hospital & Research centre A unit of SIDS health care private limited, Near shell petrol pump Ring road-sosyo circle lane, Surat-395002, Gujarat, India.
Surat
GUJARAT 
9537799664

rmgastro@yahoo.com 
Dr Dharmesh Kapoor  Yashoda Hospital  Secunderabad Hyderabad-500003, Telangana, India.
Hyderabad
TELANGANA 
9849439407

dharmesh_kapoor@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 18  
Name of Committee  Approval Status 
BAPS Hospital Institutional Ethics Committee BAPS Pramukh Swami Hospital Adajan Cross Road, Adajan Surat Surat Gujarat - 395009 India  Approved 
Drug Trial Ethics Committee Dayanand Medical College and Hospital, Civil Lines, Ludhiana, 141001, Punjab, India  Approved 
Ethics Committee S.M.S. Medical College and Attached Hospitals J.L.N. Marg Jaipur Jaipur Jaipur Rajasthan - 302004 India  Approved 
IEC Fortis Hospital Mohali Fortis Hospital Mohali Sector - 62 Phase VIII Mohali SAS Nagar Punjab - 160062 India  Approved 
Inst.Ethics committee for MV Hospital MV Hospital And Research Centre 314/30, Mirza Mandi Chowk Lucknow- Uttar Pradesh Lucknow Lucknow Uttar Pradesh - 226003 India  Approved 
Institute Ethics Committee All india institute of medical sciences Old OT block, room no. 102, aiims hospital ansari nagar, new delhi-29 new delhi south delhi delhi - 110029 india  Approved 
Institutional Ethics Committee Global Hospital,Room No.222, 2nd Floor, Dr. E. Borges Road,Hospital Avenue, Opp. Dr Shirodkar High School, Parel, Mumbai, Maharashtra – 400012, India  Approved 
Institutional ethics committee Midas multispeciality hospital pvt ltd Midas multispeciality hospital, midas height 07 central Bazar road, ramdaspeth nagpur nagpur Maharashtra - 440010 india  Approved 
Institutional ethics committee Post graduate institute of medical education and research,room no. 6006, iec office, 6th floor p n chuttani Block chandigarh chandigarh chandigarh - 160012 India  Approved 
Institutional Ethics Committee, Institute of Liver and Biliary Sciences D-1 Vasant Kunj, New Delhi -110070, India  Approved 
Institutional Ethics Committee, Ramdevrao Hospital (A unit of Sivananda Rehabilitation Home), Kukatpally, Hyderabad-500072. Telangana. India.  Approved 
Institutional Ethics Committee-l Seth GS Medical College and KEM Hospital, Mumbai. Acharya Donde Marg, Parel, . Mumbai 400 012. India Mumbai Mumbai City Maharashtra - 400012 India  Submittted/Under Review 
Institutional Ethics Committee  Osmania Medical College, Koti, Hyderabad – 500 095, Telangana, India  Approved 
MAHE Ethics Committee Manipal, Manipal Academy of Higher Education(MAHE) Manipal, Udupi-576104, Karnataka, India  Approved 
Medanta Institutional Ethics Committee Medanta The Medicity , Sector 38, Gurgaon, Haryana - 12001  Approved 
S.R.Kalla Memorial Ethical Committee For Human Research, S.R.KallaMemorial Gastro General Hospital 78-79 Dhuleshwar Garden Behind HSBC Bank Sardar Patel Marg C-Scheme Jaipur Jaipur Rajasthan - 302001 India  Approved 
Surat Institute of Digestive Science Ethics Committee SIDS Hospital & Research centre A unit of SIDS health care private limited, Near shell petrol pump Off Ring Road, Near Shell petrol pump, Ring road-sosyo circle lane, Surat-395002, Gujarat, India.  Approved 
Yashoda Academy of Medical Education and Research Yashoda hosptials Behind Hari Hara kala Bhawan Alexander Road Secunderabad Hyderabad Telangana - 500003 India  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K740||Hepatic fibrosis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Semaglutide Ia & Ib Placebo   0.5mg , 1mg, 2mg ,2.27mg & 3.2mg Once Weekly (OW) Subcutaneous till 5 years  
Intervention  Semaglutide D   0.5mg , 1mg, 2mg ,2.27mg & 3.2mg Once Weekly (OW) Subcutaneous till 5 years  
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Subjects are eligible to be included in the trial only if all of the following criteria apply:
1. Informed consent obtained before any trial-related activities. Trial-related activities are any
procedures that are carried out as part of the trial, including activities to determine suitability for
the trial except for protocol-defined pre-screening activities, which require a separate informed
consent. Ireland: See local requirements in Appendix 9 (Section 10.9).
2. Age above or equal to 18 years at the time of signing informed consent. Japan, South Korea
and Taiwan: See local requirements in Appendix 9 (Section 10.9).
3. Histological evidence of NASH based on a central pathologist evaluation of the baseline liver
biopsy. The baseline liver biopsy can be a historical biopsy obtained within 180 days prior to
screening visit (V1).
4. Histological evidence of fibrosis stage 2 or stage 3 according to the NASH CRN classification
based on a central pathologist evaluation of the baseline liver biopsy.
5. A histological NAS ≥ 4 with a score of 1 or more in steatosis, lobular inflammation and
hepatocyte ballooning based on a central pathologist evaluation of the baseline liver biopsy.
China: See local requirements in Appendix 9 (Section 10.9).
 
 
ExclusionCriteria 
Details  Positive HBsAg, positive anti-HIV, positive HCV-RNA at screening or any known presence of
HCV RNA or HBsAg within 2 years of screening (V2A).
Documented causes of chronic liver disease other than Non-Alcoholic Fatty Liver Disease
NAFLD.
Presence or history of ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial
peritonitis or liver transplantation at randomisation.
Known or suspected excessive consumption of alcohol (greater than 20 g/day for women or greater than 30 g/day for men) or alcohol dependence (assessed by the Alcohol Use Disorders Identification Test(AUDIT questionnaire).
Treatment with vitamin E (at doses greater or equal to 800 IU/day) or pioglitazone or medications approved for treatment of NASH which has not been at a stable dose in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical
liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.
Treatment with GLP-1 RAs in the period from 90 days prior to the screening visit (V2A). In
addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, any treatment with GLP-1 RAs from time of biopsy until screening.
Treatment with glucose lowering agent(s) (other than GLP-1 RAs), lipid lowering medication or
weight loss medication not stable in the opinion of the investigator in the period from 90 days prior to the screening visit (V2A). In addition, for subjects with historical liver biopsies taken more than 90 days prior to screening, treatment should be at a stable dose in the opinion of the investigator from time of biopsy until screening.
 
 
Method of Generating Random Sequence   Stratified randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
Resolution of steatohepatitis and no worsening of liver fibrosisa.
Improvement in liver
fibrosis and no worsening
of steatohepatitis.
Time to first liver-related clinical event


 
Week 0 to Week 72


 
 
Secondary Outcome  
Outcome  TimePoints 
Progression of liver fibrosis
Change in body weight
Change in SF-36 Bodily Pain
 
Week 0 to Week 72
Week 0 to Week 240
 
 
Target Sample Size   Total Sample Size="1200"
Sample Size from India="60" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/04/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  01/04/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="4"
Months="11"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Closed to Recruitment of Participants 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   Nil 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary
Modification(s)  
 
 This is a randomised, multicentre, double-blinded, parallel-group, trial comparing semaglutide s.c.
 2.4 mg once weekly versus placebo s.c. once weekly in subjects with NASH and F2 or F3
 (recruitment cap of approximately 20% for subjects with fibrosis stage 2). Approximately 6150
 subjects will be screened to achieve 1200 subjects randomly assigned to trial product. Subjects
 will be randomised 2:1 to receive either treatment with semaglutide s.c. or placebo.
  Randomisation will be stratified based on the presence of T2D at screening
 (defined as a medical history of T2D and/or HbA1c greater or equal to 48 mmol/mol
 (greater or equal to 6.5 %)), fibrosis stage and region. For both semaglutide s.c. and
  placebo there will be a period of dose escalation before reaching the target dose.
 The total trial duration for each subject is approximately 257 weeks (~4 years and 11 months).
 This includes a screening period of approximately 14 weeks followed by randomisation and
 a 240-week treatment period.
 The follow-up period is 7 weeks.
 
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