| CTRI Number |
CTRI/2019/06/019817 [Registered on: 21/06/2019] Trial Registered Prospectively |
| Last Modified On: |
21/03/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
A research study to look at how semaglutide compared to placebo affects diabetic eye disease in people with type 2 diabetes (FOCUS) |
Scientific Title of Study
Modification(s)
|
Long-term effects of semaglutide on diabetic
retinopathy in subjects with type 2 diabetes (FOCUS) |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Registry |
| NCT03811561 |
ClinicalTrials.gov |
| NN9535-4352, Version 6.0 Dated 29 July 2022 |
Protocol Number |
| U1111-1201-6256 |
UTN |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Address |
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 |
9911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
Details Contact Person
Public Query
Modification(s)
|
| Name |
Dr Maya Sharma |
| Address |
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 |
9911497869 |
| Fax |
|
| Email |
yrms@novonordisk.com |
|
|
Source of Monetary or Material Support
|
| Novo Nordisk A/S-Novo Allé, 2880 Bagsvaerd Denmark. |
|
|
Primary Sponsor
|
| Name |
Novo Nordisk AS |
| Address |
Novo Nordisk A/S-Novo Allé, 2880 Bagsvaerd Denmark. |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Novo Nordisk India Pvt Ltd |
Novo Nordisk -Plot No.32, 47 - 50, EPIP Area, Whitefield
Bangalore Karnataka-560 066 |
|
|
Countries of Recruitment
|
Brazil
Bulgaria
Canada
Czech Republic
Germany
India
Israel
Lithuania
Mexico
Poland
Portugal
Romania
Russian Federation
Serbia
Slovakia
Spain
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 17 |
| Contact Person |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Satinath Mukhopadhay |
IPGMER and SSKM Hospital |
Department of Endocrinology IPGMER and SSKM Hospital Ronald Ross Building, 4th Floor Kolkata West Bengal 700020
Kolkata
|
9830027985
satinath.mukhopadhyay@gmail.com |
| Dr Nikhil M Bhagwat |
T. N . Medical College and B Y L Nair Charitable Hospital |
Department of Endocrinology, Room no 419, 4th Floor College Building, , Dr. A L Nair Hospital, Mumbai Central, Mumbai Maharastra 400 008
Mumbai
|
9820238399
bhagwatnik@yahoo.co.in |
| Dr Jubin Jagan Jacob |
Christian Medical College and Hospital |
Department of Endocrinology Clinical Trial Unit/Endocrine and Diabetes Unit, Department of Medicine Ludhiana Punjab 141008
Ludhiana
|
9915281219
jubbin.jacob@gmail.com |
| Dr Nikhil Tandon |
All India Institutes of Medical Sciences |
Seminar Room, AB 6 Ward, 6th Floor, Ward Block Ansari Nagar New Delhi Delhi 110029
New Delhi
|
9818211663
nikhil_tandon@hotmail.com |
| Dr Vaishali Deshmukh |
Deenanath Mangeshkar Hospital and Research Centre |
SS Building Ground Floor, Endocrinology Department, Erandwane Pune Maharastra 411004
Pune
|
9850811450
drvaishaliresearch@gmail.com |
| Dr Harish Kumar |
Amrita Institute of Medical Sciences |
Department of Endocrinology, Healthcare Education and Research, AIMS- Ponekkara Kochi Kerala 682041
Ernakulam
|
9895545190
harishkumar@aims.amrita.edu |
| Dr V Mohan |
Madras Diabetes Research Foundation |
Department of Endocrinology,No.4, Conran Smith Road Gopalapuram Chennai Tami Nadu 600086
Chennai
|
04443968888
drmohans@diabetes.ind.in |
| Dr Bandgar Tushar Ramakrishna |
Seth G S medical college & KEM Hospital |
Department of Endocrinology, Parel, Mumbai, Maharastra -400012
Mumbai
|
9820025037
drtusharb@gmail.com |
| Dr Arthur Joseph Asirvatham |
Arthur Asirvatham Hospital |
Department of Endocrinology ,A- Kuruvikaran Salai Anna Bus Stand Madurai Tami Nadu 625020
Madurai
|
9443751977
ajasirvathamresearch@yahoo.in |
| Dr Bipin Kumar Sethi |
Care Out Patient Centre |
Department of Endocrinology, 8-2-620/A-E, Road No.10 Banjara Hills Hyderabad Andra Pradesh 500 034
Hyderabad
|
9848021482
sethibipin54@gmail.com |
| Dr Tirthankar Chaudhury |
Apollo Gleneagles Hospitals |
Department of Clinical Trials & Research, Apollo Gleneagles Hospitals, 58, Canal Circular Road, Kolkata-700054
Kolkata
|
9831322394
tchaudhury67@yahoo.co.uk |
| Dr Subramanian Kannan |
Mazumdar Shaw Medical Centre |
Department of Endocrinology, Consultant Endocrinologist,
Mazumdar Shaw Medical Centre,
Unit of Narayana Hrudayalaya Limited,
258/A, Bommasandra Industrial Area,
Anekal TK Bangalore-560099
Bangalore
|
8095084568
subramanian.kannan@gmail.com |
| Dr Aravind R Sosale |
Diacon Hospital Pvt Ltd |
#360, 19th Main, 1st Block, Rajajinagar, Bangalore- 560010, India
Bangalore
|
8023130577
draravindsr.pi@gmail.com |
| Dr Jabbar Puthiya Veettil Khader |
Indian Institute of Diabetes |
Indian Institute of Diabetes, Pulayanarkotta, Thiruvananthapuram-695031, Kerala
Thiruvananthapuram
|
9446828766
drjabbar10@gmail.com |
| Dr Kongara Srikanth |
Endolife Hospital |
1st floor, Clinical Research Department, Endolife Hospital, Old Club Rd, Kothapeta, Guntur, Andhra Pradesh 522001, India
Guntur
|
9849945577
srikanthendo@gmail.com |
| Dr S K Wangnoo |
Indraprastha Apollo Hospital |
Apollo Hospital, Chennai - Room No 4169,1st Floor, Delhi Highway, Mathura Rd, Saritha Vihar, New Delhi-110076
New Delhi
|
9810113922
subhashwang@hotmail.com |
| Dr Chandrasekhar Atkar |
Government Medical College and Hospital |
Medical Research Room, 2nd floor, beside ward no 48, Government Medical College and Hospital, Medical College Square Road, Nagpur-440003, Maharashtra, India
Nagpur
|
9579404986
cmatkar92@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 17 |
| Name of Committee |
Approval Status |
| Diacon Hospital Ethics Committee |
Approved |
| Drug Trial Ethics Committee |
Approved |
| Institutional Ethics Committee Indian Institute of Diabetes |
Approved |
| Institutional Ethics Committee of Endolife Specialty Hospitals Pvt Ltd |
Approved |
| Institutional Ethics Committee of Madras Diabetes Research Foundation |
Approved |
| Institutional Ethics Committee, Christian Medical College and Hospital |
Approved |
| Institutional Ethics Committee, AIIMS |
Approved |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences & Research Centre |
Approved |
| Institutional Ethics Committee, Apollo Gleneagles |
Approved |
| Institutional Ethics Committee, Arthur Asirvatham Hospital |
Approved |
| Institutional Ethics Committee, CARE Foundation |
Approved |
| Institutional Ethics Committee, Clinical studies, Indraprastha Apollo Hospitals |
Approved |
| Institutional Ethics Committee, Deenanath Mangeshkar Hospital and Research Centre |
Approved |
| Institutional Ethics Committee, Government Medical College & Hospital |
Approved |
| Institutional Ethics Committee,T. N . Medical College and B Y L Nair Charitable Hospital |
Approved |
| Institutional Ethics Committee- I, Seth G.S. Medical College and KEM Hospital |
Submittted/Under Review |
| Narayana Health Medical Ethics Committee |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Type 2 diabetes mellitus |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo
|
Dose: Subjects will be initiated at a once-weekly dose of 0.25 mg s.c. and follow a fixed-dose escalation
regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0 mg/week), to improve glycemic control as judged by the investigator
Duration: Trial duration for each subject will be five years (260 weeks) plus the follow-up period which is
five weeks after end-of-treatment.
|
| Intervention |
Semaglutide
|
Dose: Subjects will be initiated at a once-weekly dose of 0.25 mg s.c. and follow a fixed-dose escalation
regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0 mg/week), to improve glycemic control as judged by the investigator
Duration: Trial duration for each subject will be five years (260 weeks) plus the follow-up period which is
five weeks after end-of-treatment.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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.
2. Male or female, age ≥18 years at the time of signing informed consent.
3. Diagnosed with type 2 diabetes mellitus ≥ 10 years prior to the day of screening.
4. HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive).
Eye inclusion criteria (both eyes must meet all criteria):
5. ETDRS level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by
central reading centre.
6. No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema twelve
months prior to the day of screening.
7. No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic
macular oedema within six months after randomisation.
8. Best-corrected visual acuity ≥30 letters using the ETDRS visual acuity protocol.
9. No previous treatment with pan-retinal laser photocoagulation
10. No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would
impact diabetic retinopathy or diabetic macular oedema progression during the trial.
11. No substantial media opacities that would preclude successful imaging.
|
|
| ExclusionCriteria |
| Details |
Subjects are excluded from the trial if any of the following criteria apply:
1. Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening.
2. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
3. Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
4. Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of
eGFR less than 30 ml per min per 1.73 m2.
5. Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
6. Presence or history of malignant neoplasms within the past 5 years prior to the day of screening.
Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
7. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods.
8. Current or previous (within 30 days before screening) treatment with any GLP-1 receptor agonist or DPP-4 inhibitor.
9. Receipt of any investigational medicinal product within 30 days before screening.
10. Previous participation in this trial. Participation is defined as randomisation.
11. Known or suspected hypersensitivity to trial products or related products.
12. Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or
compliance with the protocol.
Based on medical history using latest available and no more than 6 months old assessment. If not available in medical records a local laboratory measurement must be made available before randomisation.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
The primary endpoint is presence of more than or equal to 3 steps ETDRS (Early Treatment Diabetic Retinopathy
Study) subject level progression at year 5. |
5 Years |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
· ciDME in either eye at year 5 (yes/no)
Change from baseline at year 5 in:
· HbA1c (%-point)
· Body weight (kg)
· Systolic and diastolic blood pressure (mmHg)
· Lipids: Total-cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides (mmol/L)
|
5 Years |
Confirmatory Secondary Endpoints/Outcomes-Time from randomisation to first more than or equal to 3 steps ETDRS subject level progression or ciDME in either eye
(month).
|
5 Years |
Occurrence of treatment for diabetic retinopathy or diabetic macular oedema in either eye during the period from randomisation to year 5 with:
· Focal/grid laser photocoagulation (yes/no)
· Pan-retinal laser photocoagulation (yes/no)
· Intravitreal injection with anti-VEGF (yes/no)
· Intravitreal injection with steroid (yes/no)
· Vitrectomy (yes/no)
|
5 Years |
Persistent more than or equal to 2 lines (10 letters) ETDRS improvement in visual acuity in either eye from baseline
at year 5 (yes/no)
· Persistent more than or equal to 3 lines (15 letters) ETDRS improvement in visual acuity in either eye from baseline
at year 5 (yes/no
|
5 Years |
Persistent visual acuity less than or equal to 38 ETDRS letters in either eye at year 5 (yes/no)
· Persistent more than or equal to 2 lines (10 letters) ETDRS worsening in visual acuity in either eye from baseline at
year 5 (yes/no)
· Persistent more than or equal to 3 lines (15 letters) ETDRS worsening in visual acuity in either eye from baseline at
year 5 (yes/no)
|
5 Years |
Presence of:
· more than or equal to 3 ETDRS subject level improvement at year 5 (yes/no)
· more than or equal to 2 steps ETDRS subject level progression at year 5 (yes/no)
· more than or equal to 2 steps ETDRS subject level improvement at year 5 (yes/no)
|
5 Years |
Supportive secondary outcome/Change from baseline at year 5 in:
· Visual acuity in the worse seeing eye (number of letters)
· Visual acuity in the better seeing eye (number of letters)
|
5 Years |
|
|
Target Sample Size
|
Total Sample Size="1500"
Sample Size from India="150" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
24/06/2019 |
| Date of First Enrollment (Global) |
08/05/2019 |
|
Estimated Duration of Trial
|
Years="4"
Months="11"
Days="30" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
Publication Details
Modification(s)
|
not yet |
|
Brief Summary
|
This trial is a 5 year long randomised, double-masked, parallel-group, placebo-controlled trial comparing the effects of semaglutide versus placebo both administered subcutaneously once-weekly and added to standard-of-care in subjects with inadequately controlled T2D. Subjects will be randomised 1:1 to receive either semaglutide or placebo and stratified based on diabetic retinopathy severity at baseline. |
