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CTRI Number  CTRI/2020/03/023899 [Registered on: 12/03/2020] Trial Registered Prospectively
Last Modified On: 25/02/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug
Biological 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   Safety, Tolerability, Efficacy and Dose-response of GSK2831781 in Ulcerative Colitis 
Scientific Title of Study   A multicentre randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety, tolerability, efficacy, dose-response, pharmacokinetics and pharmacodynamics of repeat dosing of an anti-LAG3 cell depleting monoclonal antibody (GSK2831781) in patients with active ulcerative colitis 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
GSK204869  Protocol Number 
NCT03893565  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ruth Tarzi  
Designation  GSK2831781 Clinical Development Lead 
Affiliation  GlaxoSmithKline 
Address  Dr Ruth Tarzi, BM BCh PhD FRCP, GSK2831781 Clinical Development Lead Department: GlaxoSmithKline Clinical Science (II and Fibrosis)
Gunnels Wood Rd, Stevenage SG1 2NY, Hertfordshire, United Kingdom


SG1 2NY
Other 
Phone  00441438761437  
Fax    
Email  ruth.m.tarzi@gsk.com  
 
Details of Contact Person
Scientific Query  
Name  Sandesh Brahmankar 
Designation  Head, Project Operations India 
Affiliation  George Clinical India Private Limited 
Address  George Clinical A division of The George Institute for Global Health, Department - Clinical Operations Department, Room - Project Operations
Plot No. 5, Prestige Khoday Towers, 12th Floor, Raj Bhavan Road, Bangalore - 560 001 Karnataka, India
Bangalore
KARNATAKA
560001
India 
Phone  918049421400   
Fax  918049421426  
Email  sbrahmankar@georgeclinical.com  
 
Details of Contact Person
Public Query  
Name  Vanaja Krishnan 
Designation  Managing Director, India 
Affiliation  George Clinical India Private Limited 
Address  George Clinical A division of The George Institute for Global Health, Department - Managing Director Room - Management Room
Plot No. 5, Prestige Khoday Towers, 12th Floor, Raj Bhavan Road, Bangalore - 560 001 Karnataka, India
Bangalore
KARNATAKA
560001
India 
Phone  918049421400   
Fax  918049421426  
Email  vkrishnan@georgeclinical.com  
 
Source of Monetary or Material Support  
GlaxoSmithKline Research and Development Limited 1-3 Iron Bridge Road, Stockley Park West UB11 1BT Uxbridge, Middx United Kingdom 
 
Primary Sponsor  
Name  GlaxoSmithKline Research Development Limited 
Address  980 Great West Road Brentford Middlesex TW8 9GS UK 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Canada
Belgium
Bulgaria
Czech Republic
Estonia
France
Hungary
India
Japan
Mexico
Netherlands
Poland
Republic of Korea
Russian Federation
Serbia
Slovakia
South Africa
Ukraine
United Kingdom
United States of America  
Sites of Study  
No of Sites = 8  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ajit Sood  Dayanand Medical College and Hospital  Dr. Ajit Sood Consultation Room Dayanand Medical College and Hospital Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India
Ludhiana
PUNJAB 		 911612300791

ajitsood10@gmail.com 
Dr Ajay Bhalla  Fortis Hospital Noida  Dr. Ajay Bhalla , second Floor, Consultation Room Fortis Hospital, B22, Sector 62 Noida 201301, Uttar Pradesh, India
East
DELHI 		 911612300791

ajay.bhall@fortishealthcare.com 
Dr Shrikant Vasant Mukewar  Midas institute of Gastroenterology  Dr. Shrikant Vasant Mukewar Consultation Room, Midas institute of Gastroenterology, Midas height, 07 Central Bazar Road, Ramdaspeth,440010
Nagpur
MAHARASHTRA 		 7720033280

shrikant_mukewar@yaoo.com 
Dr Mukesh Kalla  S. R. Kalla Memorial Gastro & General Hospital  Dr. Mukesh Kalla, Consultation Room S. R. Kalla Memorial Gastro & General Hospital 78, Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C Scheme, Jaipur 302001, Rajasthan, India
Jaipur
RAJASTHAN 		 911414039432

drmkalla@rediffmail.com 
Dr Sandeep Kulkarni  Sahyadri Specialty Hospital  Dr. Sandeep Kulkarni, Consultation Room Sahyadri Specialty Hospital 30C, Erandwane, Karve road, Pune 411004, Maharashtra, India
Pune
MAHARASHTRA 		 912067213000

drsandeepkul@yahoo.com 
Dr Hemant Gupta  Samvedana Hospital - Varanasi  Dr. Hemant Gupta, Ground Floor, Consultation Room Samvedana Hospital, B-27 88G New Colony, Ravindra Puri
Varanasi
UTTAR PRADESH 		 9415336365

hemantg26@yahoo.com 
Dr Chetan Mehta  Shree Giriraj Multispeciality Hospital  Dr. Chetan Mehta Department of Consultation Room Gastroenterology, 27 Navjyot Park Corner, 150 Feet Ring Road, Rajko 360 005
Rajkot
GUJARAT 		 9825077472

mehtach@hotmail.com 
Dr Naresh Bansal  Sir Ganga Ram Hospital  Dr. Naresh Bansal, Consultation Room Clinical Research Department 6th Floor, Sir Ganga Ram Hospital, Sir Ganga Ram Hospital Marg Rajinder Nagar
New Delhi
DELHI 		 93102466832

drnbansal@ymail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 8  
Name of Committee  Approval Status 
Dayanand Medical College & Hospital Drug Trial Ethics committee   Approved 
Institutional Ethics Committee Fortis Hospital   Submittted/Under Review 
Institutional Ethics Committee, Midas Multispeciality Hospital Pvt. Ltd.  Approved 
Sahyadri Hospitals Limited Ethics Committee  Approved 
Samvedana Hospital Ethics Committee   Approved 
Sir Ganga Ram Hospital Ethics Committee  Submittted/Under Review 
SR Kalla Memorial Ethical Committee for Human Research  Approved 
Sri Giriraja Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K518||Other ulcerative colitis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Biological: GSK2831781  Subjects will receive different doses of GSK2831781 during Induction and Maintenance Phase 
Comparator Agent  Drug: Placebo  Commercial saline solution will be administered as placebo during Induction and Maintenance Phase 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  Participants are eligible to be included in the study only if all the following criteria apply

AGE and WEIGHT

Participant must be 18 years of age or older and >40kg at the time of signing the informed consent.
TYPE OF PARTICIPANT AND DISEASE CHARACTERISTICS
Participants who have a:

Diagnosis of ulcerative colitis, established at least 3 months prior to screening, as documented by diagnostic sigmoidoscopy or colonoscopy, and biopsy.

Complete Mayo Score of 6 to 12, with disease extending ≥15cm from the anal verge, with a centrally read endoscopic subscore of ≥2 at screening endoscopy, and a rectal
bleeding subscore ≥1.

A history of at least one of the following:

Inadequate response to, loss of response to, or intolerance to azathioprine or mercaptopurine (including thiopurine methyltransferase (TPMT) genetic
mutation precluding use), ciclosporin, tacrolimus or methotrexate.

Inadequate response to, intolerance to, or demonstrated dependence on oral corticosteroids.

Inadequate response to, loss of response to, or intolerance to one biologic class ONLY for the treatment of UC: either one or more anti-TNF therapies
(e.g. infliximab, adalimumab, golimumab, or biosimilar) OR vedolizumab.

Surveillance colonoscopy (performed according to local standards) within 12 months of screening (or during screening, if required) for participants with:
Pancolitis of >8 years duration; or
Patients with left-sided colitis of >12 years duration; or
Patients with primary sclerosing cholangitis.
For patients for whom this criterion does not apply, colorectal cancer surveillance should be undertaken according to local or national guidelines for patients with age ≥50, or with other known risk factors for colorectal
cancer.

SEX
Female participants:
A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

Not a woman of childbearing potential (WOCBP), see Section 10.4.1,
WOCBP definitions.
OR
A WOCBP who agrees to use a highly effective contraceptive method for at least 4 weeks prior to dosing, until the Follow-Up visit. See Section 10.4.2, Contraceptive Guidance.

INFORMED CONSENT
Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form
(ICF) and in this protocol. 
 
ExclusionCriteria 
Details  Participants with a current diagnosis of indeterminate colitis, inflammatory bowel
disease-unclassified, Crohn’s disease, infectious colitis, or ischaemic colitis.
Participants with fulminant ulcerative colitis (as defined by 6 bloody stools daily
AND 1 or more of: i) body temperature ≥100.4°F (or 38°C) or ii) heart rate >90 beats
per minute), or toxic megacolon.
Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or
planned surgery for UC.
Participants with any uncontrolled medical conditions, other than active UC, that in
the opinion of the investigator put the participant at unacceptable risk or interfere
with study assessments or integrity of the data. Other medical conditions should be
stable at the time of screening and be expected to remain stable for the duration of
the study.
Unstable lifestyle factors, such as alcohol use to excess or recreational drug use, to
the extent that in the opinion of the investigator they would interfere with the ability
of a participant to complete the study.
An active infection or a history of serious infections as follows:
- Use of antimicrobials (antibacterials, antivirals, antifungals or antiparasitic agents)
for an infection within 30 days before first dose (topical treatments may be
allowed at the Medical Monitor’s discretion).
- A history of opportunistic infections within 1 year of screening (e.g. Pneumocystis
jirovecii, aspergillosis or CMV colitis). This does not include infections that may
occur in immunocompetent individuals, such as fungal nail infections or vaginal
candidiasis, unless it is of an unusual severity or recurrent nature.
- Recurrent or chronic infection or other active infection that, in the opinion of the
Investigator, might cause this study to be detrimental to the patient.
- Symptomatic herpes zoster within 3 months prior to screening.
- History of tuberculosis (active or latent), irrespective of treatment status.
- A positive diagnostic TB test at screening (defined as a positive QuantiFERON
test). In cases where the QuantiFERON test is indeterminate, the participant may
have the test repeated once and if their second test is negative they will be
eligible. In the event a second test is also indeterminate, the investigator has the
option to undertake PPD testing. If the PPD reaction is <5 mm, then the
participant is eligible. If the reaction is ≥5 mm, or PPD testing is not undertaken,
the participant is not eligible.
- Positive Clostridium difficile toxin test during screening. However, rescreening
can be undertaken following successful treatment.
Current or history of chronic liver or biliary disease (with the exception of Gilbert’s
syndrome, asymptomatic gallstones or uncomplicated fatty liver disease).
Hereditary or acquired immunodeficiency disorder, including immunoglobulin
deficiency (unless the participant has a documented history of selective IgA
deficiency).
A major organ transplant (e.g. heart, lung, kidney, liver, pancreas) or haematopoietic
stem cell/marrow transplant.
Any planned major surgical procedure during the study.
A history of malignant neoplasm within the last 5 years, except for adequately
treated non-metastatic basal or squamous cell cancers of the skin (within 1 year) or
carcinoma in situ of the uterine cervix (within 3 years) that has been fully treated and
shows no evidence of recurrence. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Main Objective - To evaluate the safety and tolerability of repeat doses of GSK2831781
- To characterise the efficacy dose response of GSK2831781 during the Induction Phase.
 		 Week 10
 
 
Secondary Outcome  
Outcome  TimePoints 
To investigate the
- Effect of repeat doses of GSK2831781 on clinical efficacy including endoscopic mucosal healing during the Induction Phase
- Effect of repeat doses of GSK2831781 on UC histologic disease activity during the Induction Phase
- Effect of repeat doses of GSK2831781 on biomarkers of UC disease activity during the Induction Phase
- Pharmacokinetics of GSK2831781 following repeat intravenous and subcutaneous dosing
- Immunogenicity of repeat doses of GSK2831781 		 Week 10 (mayo score) and end of study (safety endpoints) 
Proportion of participants who achieve
-Mayo endo score of 0 or 1 at Wk 10
-Mayo clinical remission at Wk 10
Change from baseline in
-partial Mayo score over time
-Mayo endo score & UCEIS at Wk 10
-histological severity at Wk 10 as determined by
Robarts Histopathology Index
Nancy Histological Index
Geboes Score
-Serum C reactive protein over time
-faecal calprotectin over time
 		 Week 10 mayo score and end of study safety endpoints 
 
Target Sample Size   Total Sample Size="320"
Sample Size from India="40" 
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 2 
Date of First Enrollment (India)   20/03/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  18/09/2019 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="1"
Days="0" 
Recruitment Status of Trial (Global)   Open to Recruitment 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   A manuscript will be progressed for publication in the scientific literature if the results provide important scientific or medical knowledge. 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary   Ulcerative colitis is a form of inflammatory bowel disease characterized by chronic relapsing and remitting inflammation of the colon and rectum. There remains a high unmet need for novel treatments that achieve a higher rate of efficacy in resolving disease symptoms, and inducing and maintaining mucosal healing to achieve long-term corticosteroid-free remission. T cells are integral to the pathogenesis of ulcerative colitis, and clinical experience with anti-integrin monoclonal antibodies has established the principle of T cell-targeted therapies in the disease. GSK2831781 causes targeted depletion of Lymphocyte activation gene-3 (LAG3+) T cells, and has shown preliminary evidence of clinical efficacy in plaque psoriasis. It is therefore hypothesized that GSK2831781 will selectively deplete activated mucosal T cells in ulcerative colitis, but with relative sparing of resting T cells. This study will investigate the safety, tolerability, efficacy and dose-response of GSK2831781 in subjects with moderate to severe active ulcerative colitis. The study consists of a 5-week screening window, 10-week Induction Phase, 20-week Extended Treatment Phase, and a 12-week Follow-Up Phase. Non-Responders allocated to open label treatment who subsequently respond to treatment may spend up to 54 weeks in total on study. Approximately 280 subjects will be included in the study.  
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