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Trial record 1 of 2 for:    204869
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Safety, Tolerability, Efficacy and Dose-response of GSK2831781 in Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03893565
Recruitment Status : Recruiting
First Posted : March 28, 2019
Last Update Posted : September 15, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
Ulcerative colitis (UC) 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 is a Phase 2, multicenter, randomized, double-blind, parallel group, placebo-controlled study to investigate the safety, tolerability, efficacy and dose-response of GSK2831781 in participants with moderate to severe active ulcerative colitis. The study consists of a 5-week screening window, 10-week Induction Phase, 30-week double-blind Extended Treatment Phase (ETP) with 42-week Follow-Up Phase. Non-Responders identified following the Week 10 assessment will be allocated to open label treatment, consisting of Induction (Weeks 12 to 22), an Open label ETP (Weeks 22 to 42) and a follow-Up to Week 54. Approximately 242 participants will be included in the study.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: GSK2831781 IV infusion Drug: GSK2831781 SC injection Drug: Placebo IV infusion Drug: Placebo SC injection Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants will be initially randomized in 2:1 ratio to receive GSK2831781 or Placebo. Further, randomization to (GSK2831781 Dose Level 1 to 4 IV [intravenously] or placebo) will be done at a ratio of 2:3:3:3:2 for a double-blind induction phase. Week 10 Responders will receive subcutaneous (SC) doses of GSK2831781 every 4 weeks (q4w). Responders in placebo treatment arm will continue to receive blinded placebo through SC dosing in a double-blind ETP. Non-responders to double blind induction phase at Week 10 will switch to open label induction where they will be administered same induction dosing schedule of GSK2831781 from Week 12 to 22 followed by an open label ETP (Weeks 22 to 42) and a follow-up to Week 54. Open-label induction phase participants will be assessed for responder status at Week 22. Responders from this phase will receive GSK2831781Maintenance dosing SC q4w until Week 38, while Non-Responders to open label ETP will discontinue treatment.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double-blind study. Induction doses will be matched with placebo. For Maintenance dosing, participant and investigator will be masked. Participants will be allocated to the next treatment phase according to their Responder status. Non-responders to the double-blind Induction Phase will receive treatment in Open-Label Induction phase where there will be no masking.
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 6, 2019
Estimated Primary Completion Date : July 11, 2022
Estimated Study Completion Date : May 17, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GSK2831781 dose 1
Eligible participants will receive GSK2831781 IV in the double blind induction phase at Week 0, 2, 6, and 10. Participants identified as Responders at Week 10 will then receive GSK2831781 SC q4w during the double-blind ETP from Week 14 until Week 26. Participants identified as Non-Responders at Week 10 will be allocated to open label induction phase to receive GSK2831781 IV from Week 12 until Week 22. Participants identified as Responders at Week 22 will enter open label ETP to receive GSK2831781 SC q4w from Week 26 until Week 38. Participants identified as Non- Responders at Week 22 will discontinue treatment.
Drug: GSK2831781 IV infusion
GSK2831781 will be administered intravenously according to randomization in the induction phase of double blind as well as open label phases.

Drug: GSK2831781 SC injection
GSK2831781 SC will be administered in the ETP of double blind and open label phase

Experimental: GSK2831781 dose 2
Eligible participants will receive GSK2831781 IV in the double blind induction phase at Week 0, 2, 6, and 10. Participants identified as Responders at Week 10 will then receive GSK2831781 SC q4w during the double-blind ETP from Week 14 until Week 26. Participants identified as Non-Responders at Week 10 will be allocated to open label induction phase to receive GSK2831781 IV from Week 12 until Week 22. Participants identified as Responders at Week 22 will enter open label ETP to receive GSK2831781 SC q4w from Week 26 until Week 38. Participants identified as Non- Responders at Week 22 will discontinue treatment.
Drug: GSK2831781 IV infusion
GSK2831781 will be administered intravenously according to randomization in the induction phase of double blind as well as open label phases.

Drug: GSK2831781 SC injection
GSK2831781 SC will be administered in the ETP of double blind and open label phase

Experimental: GSK2831781 dose 3
Eligible participants will receive GSK2831781 IV in the double blind induction phase at Week 0, 2, 6, and 10. Participants identified as Responders at Week 10 will then receive GSK2831781 SC q4w during the double-blind ETP from Week 14 until Week 26. Participants identified as Non-Responders at Week 10 will be allocated to open label induction phase to receive GSK2831781 IV from Week 12 until Week 22. Participants identified as Responders at Week 22 will enter open label ETP to receive GSK2831781 SC q4w from Week 26 until Week 38. Participants identified as Non- Responders at Week 22 will discontinue treatment.
Drug: GSK2831781 IV infusion
GSK2831781 will be administered intravenously according to randomization in the induction phase of double blind as well as open label phases.

Drug: GSK2831781 SC injection
GSK2831781 SC will be administered in the ETP of double blind and open label phase

Experimental: GSK2831781 dose 4
Eligible participants will receive GSK2831781 IV in the double blind induction phase at Week 0, 2, 6, and 10. Participants identified as Responders during induction phase will then receive GSK2831781 SC q4w during the double-blind ETP until Week 26. Non-Responders to GSK2831781 IV at Week 10 will be allocated to open label induction phase to receive GSK2831781 IV until Week 22 and responders will enter open label ETP to receive GSK2831781 SC q4w until Week 38. Open label ETP non-responders will discontinue treatment.
Drug: GSK2831781 IV infusion
GSK2831781 will be administered intravenously according to randomization in the induction phase of double blind as well as open label phases.

Drug: GSK2831781 SC injection
GSK2831781 SC will be administered in the ETP of double blind and open label phase

Placebo Comparator: Placebo matching GSK2831781
Eligible participants will receive Placebo in the double blind induction phase at Week 0, 2, 6, and 10. Participants identified as Responders at Week 10 will continue to receive Placebo SC q4w during the double-blind ETP from Week 14 until Week 26. Participants identified as Non-Responders at Week 10 will be allocated to open label induction phase to receive GSK2831781 IV from Week 12 until Week 22. Participants identified as Responders at Week 22 will enter open label ETP to receive GSK2831781 SC q4w from Week 26 until Week 38. Participants identified as Non- Responders at Week 22 will discontinue treatment.
Drug: GSK2831781 IV infusion
GSK2831781 will be administered intravenously according to randomization in the induction phase of double blind as well as open label phases.

Drug: GSK2831781 SC injection
GSK2831781 SC will be administered in the ETP of double blind and open label phase

Drug: Placebo IV infusion
Commercial saline solution will be administered as IV solution during double blind induction phase.

Drug: Placebo SC injection
Commercial saline solution will be administered as SC injection during double blind ETP.




Primary Outcome Measures :
  1. Number of participants with adverse events (AEs) and serious adverse events (SAEs) in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment.

  2. Number of participants with abnormal vital signs in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    Vital signs including systolic and diastolic blood pressure, pulse rate and body temperature of participants will be measured in a seated or semi-supine position after 5 minutes rest.

  3. Number of participants with abnormal findings for hematology parameters in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    Blood samples will be collected from participants for the analysis of hematology parameters as a measure of safety, including platelet count, Red blood cell (RBC) count, hemoglobin, hematocrit, Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), percent reticulocytes, differential neutrophils, lymphocytes, monocytes, basophils and eosinophils.

  4. Number of participants with abnormal findings for clinical chemistry parameters in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    Blood samples will be collected from participants for the analysis of clinical chemistry parameters as a measure of safety, including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, sodium, alanine aminotransferase (ALT), total protein, glucose, calcium, alkaline phosphatase, albumin and C- reactive protein.

  5. Number of participants with abnormal findings for urine parameters in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    Urine samples will be collected from participants for the analysis of urine parameters as a measure of safety, including specific gravity and potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite and leukocyte esterase by dipstick test.

  6. Number of participants with abnormal electrocardiogram findings in the Double Blind Induction Phase [ Time Frame: Up to Week 10 ]
    12-lead electrocardiogram will be used to determine abnormal QT interval corrected for heart rate (QTc).

  7. Change from Baseline in Complete 4-domain Mayo Clinic Score (MCS) at Week 10 [ Time Frame: Baseline and Week 10 ]
    Clinical disease assessments will be undertaken using the Complete 4-Domain MCS. The Complete Mayo Score is a 12-point scoring system where disease is evaluated based on stool frequency, rectal bleeding, physician global assessment (PGA) and endoscopic appearance (with mild friability associated with an endoscopic score of 1). Each subscale is scored on a scale of 0 to 3, where 0 = normal condition and 3 = severe disease condition.


Secondary Outcome Measures :
  1. Number of participants with AEs and SAEs in the double blind ETP [ Time Frame: Up to Week 42 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment.

  2. Number of participants with abnormal vital signs in the double blind ETP [ Time Frame: Up to Week 42 ]
    Vital signs including systolic and diastolic blood pressure, pulse rate and body temperature of participants will be measured in a seated or semi-supine position after 5 minutes rest

  3. Number of participants with abnormal findings for hematology parameters in the double blind ETP [ Time Frame: Up to Week 42 ]
    Blood samples will be collected from participants for the analysis of hematology parameters as a measure of safety, including platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, percent reticulocytes, differential neutrophils, lymphocytes, monocytes, basophils and eosinophils.

  4. Number of participants with abnormal findings for clinical chemistry parameters in the double blind ETP [ Time Frame: Up to Week 42 ]
    Blood samples will be collected from participants for the analysis of clinical chemistry parameters as a measure of safety, including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, sodium, ALT, total protein, glucose, calcium, alkaline phosphatase, albumin and C- reactive protein.

  5. Number of participants with abnormal findings for urine parameters in the double blind ETP [ Time Frame: Up to Week 42 ]
    Urine samples will be collected from participants for the analysis of urine parameters as a measure of safety, including specific gravity and pH of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite and leukocyte esterase by dipstick test.

  6. Number of participants with abnormal electrocardiogram findings in the double blind ETP [ Time Frame: Up to Week 42 ]
    12-lead electrocardiogram will be used to determine abnormal QTc.

  7. Percentage of participants who achieve adapted Mayo endoscopic score of 0 or 1 at Week 10 [ Time Frame: At Week 10 ]
    Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis will be determined by adapted Mayo endoscopic score. The Adapted Mayo Score is a 9-point scoring system where disease is evaluated based on stool frequency, rectal bleeding and endoscopic appearance (with any friability associated with an endoscopic score of 2 or 3).The scores will range from 0 (Normal or inactive disease) to 3 (Severe disease or spontaneous bleeding, ulceration).

  8. Percentage of participants who achieve adapted Mayo clinical remission at Week 10 [ Time Frame: At Week 10 ]
    Clinical remission is defined as an adapted MCS of less than or equal to (<=) 2, with no individual sub score greater than (>) 1 and a rectal bleeding subscore of 0 and stool frequency subscore <=1 and not greater than Baseline at Week 10.

  9. Percentage of participants who achieve Mayo clinical response as per adapted MCS at Week 10 [ Time Frame: At Week 10 ]
    Clinical response is defined as reduction in adapted MCS greater than or equal to (>=) 2 points from Baseline and >=30 percent from Baseline and a decrease in the rectal bleeding score of >=1 point from Baseline or a score of 0 or 1.

  10. Percentage of participants who achieve symptomatic remission over time [ Time Frame: At Week 10 ]
    Symptomatic remission is defined as a rectal bleeding subscore of 0, and a stool frequency subscore of <=1, with no worsening from Baseline

  11. Change from Baseline in partial Mayo score over time [ Time Frame: Baseline and up to Week 10 ]
    Clinical disease assessments will be undertaken using the partial Mayo Score. It consists of 3 subscales: stool frequency, rectal bleeding, and/or physician's global assessment of disease activity. Each subscale is scored on a scale of 0 to 3, where 0 = normal condition and 3 = severe disease condition.

  12. Change from Baseline in adapted Mayo endoscopic score at Week 10 [ Time Frame: Baseline and up to Week 10 ]
    Improvement in endoscopic assessment of mucosal inflammation in ulcerative colitis will be determined by adapted Mayo endoscopic score on a scale ranging from 0 (Normal or inactive disease) to 3 (Severe disease or spontaneous bleeding, ulceration). The Adapted Mayo Score is a 9-point scoring system where disease is evaluated based on stool frequency, rectal bleeding and endoscopic appearance (with any friability associated with an endoscopic score of 2 or 3).

  13. Change from Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) at Week 10 [ Time Frame: Baseline and Week 10 ]
    UCEIS will be used as an additional tool to assess disease activity based on endoscopic vascular pattern, bleeding, erosions and ulcerations. Each item has 3 or 4 levels of severity and is given a score. The scores for each individual item are combined into a total score ranging from 0 to 8. A higher score indicates increased endoscopic severity of Ulcerative Colitis.

  14. Change from Baseline in histological severity as determined by the Robarts Histopathology Index at Week 10 [ Time Frame: Baseline and Week 10 ]
    The Robarts Histopathology Index will be assessed by central reading of gut pinch biopsies. Key domains for scoring of the indices include chronic inflammatory infiltrate; neutrophils in the epithelium, lamina propria neutrophils, erosion and ulceration scored from 0 to 3 and multiplied by a weighting factor. The total Robarts Histopathology Index score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity).

  15. Change from Baseline in histological severity as determined by the Nancy Histological Index at Week 10 [ Time Frame: Baseline and Week 10 ]
    The Nancy Histopathology Index will be assessed by central reading of gut pinch biopsies. Key domains for scoring of the indices include chronic inflammatory infiltrate; neutrophils in the epithelium, lamina propria neutrophils, erosion and ulceration scored from 0 to 3 and multiplied by a weighting factor. The total Nancy Histopathology Index score is calculated by summing the weighted scores of the histological items, with total scores ranging from 0 (no disease activity) to 33 (severe disease activity).

  16. Change from Baseline in histological severity as determined by Geboes Score at Week 10 [ Time Frame: Baseline and Week 10 ]
    Biopsy samples will be assessed in Geboes score ranging from 0 to 5. Lower values represent a better outcome.

  17. Change from Baseline in serum C reactive protein over time [ Time Frame: Baseline and up to Week 10 ]
    A blood sample will be collected for analysis of C reactive protein to characterize the impact of GSK2831781.

  18. Change from Baseline in fecal calprotectin over time [ Time Frame: Baseline and up to Week 10 ]
    Fecal samples will be collected for analysis of calprotectin to characterize the impact of GSK2831781 on this biomarker of intestinal inflammation.

  19. Area under the concentration-time curve over the dosing interval (AUC [0-tau]) of GSK2831781 following subcutaneous dosing [ Time Frame: At any time on Days 99, 100, 101, 102, 104, 106, 109, 127, 155, 183, 211, 295 and 379 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2831781.

  20. Maximum observed plasma concentration (Cmax) of GSK2831781 following subcutaneous dosing [ Time Frame: At any time on Days 99, 100, 101, 102, 104, 106, 109, 127, 155, 183, 211, 295 and 379 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2831781.

  21. Time to reach Cmax (Tmax) of GSK2831781 following subcutaneous dosing [ Time Frame: At any time on Days 99, 100, 101, 102, 104, 106, 109, 127, 155, 183, 211, 295 and 379 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2831781.

  22. Number of participants with anti-drug antibodies at each visit [ Time Frame: Up to Week 54 ]
    Serum samples will be assessed for the presence of anti-drug antibodies.


Other Outcome Measures:
  1. Number of participants with AEs and SAEs in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment.

  2. Number of participants with abnormal vital signs in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    Vital signs including systolic and diastolic blood pressure, pulse rate and body temperature of participants will be measured in a seated or semi-supine position after 5 minutes rest.

  3. Number of participants with abnormal findings for hematology parameters in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    Blood samples will be collected from participants for the analysis of hematology parameters as a measure of safety, including platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, percent reticulocytes, differential neutrophils, lymphocytes, monocytes, basophils and eosinophils.

  4. Number of participants with abnormal findings for clinical chemistry parameters in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    Blood samples will be collected from participants for the analysis of clinical chemistry parameters as a measure of safety, including blood urea nitrogen, potassium, aspartate aminotransferase, total bilirubin, creatinine, sodium, ALT, total protein, glucose, calcium, alkaline phosphatase, albumin and C- reactive protein.

  5. Number of participants with abnormal findings for urine parameters in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    Urine samples will be collected from participants for the analysis of urine parameters as a measure of safety, including specific gravity and pH of urine, presence of glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite and leukocyte esterase by dipstick test.

  6. Number of participants with abnormal electrocardiogram findings in the Open Label Induction and Open Label Extended Treatment Phases [ Time Frame: Up to Week 54 ]
    12-lead electrocardiogram will be used to determine abnormal QTc.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be 18 years of age or older and > 40 kilograms (kg) at the time of signing the informed consent.
  • 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 >= 15 centimeters (cm) from the anal verge, with a centrally read endoscopic sub score of >=2 at screening endoscopy, and a rectal bleeding sub score >=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, loss of response to, intolerance to, or demonstrated dependence on oral corticosteroids; inadequate response to, loss of response to, or intolerance to at least one approved advanced therapy for UC including anti- tumor necrosis factor (TNF) therapies (example given [e.g.] infliximab, adalimumab, golimumab, or biosimilar), anti-integrin therapies, anti-interleukin (IL)-12/23 monoclonal antibodies or Janus Kinase (JAK) inhibitors.
  • 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 participants with left-sided colitis of >12 years duration. For participants for whom this criterion does not apply, colorectal cancer surveillance should be undertaken according to local or national guidelines for participants with age >=50, or with other known risk factors for colorectal cancer.
  • Both male and female participants are eligible to participate.
  • 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); A WOCBP who agrees to use a highly effective contraceptive method for at least 4 weeks prior to dosing, until the Follow-Up visit.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • Participants with a current diagnosis of indeterminate colitis, inflammatory bowel disease-unclassified, Crohn's disease, infectious colitis, or ischemic colitis.
  • Participants with fulminant ulcerative colitis (as defined by 6 bloody stools daily and 1 or more of body temperature >=100.4 degrees Fahrenheit (or 38 degree Celsius) or heart rate >90 beats per minute), or toxic megacolon.
  • Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for ulcerative colitis.
  • Participants with any uncontrolled medical conditions, other than active ulcerative colitis, 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: a) 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). b) A history of opportunistic infections within 1 year of screening (e.g. Pneumocystis jirovecii, aspergillosis or Cytomegalovirus 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. c) Recurrent or chronic infection or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the participant. d) Symptomatic herpes zoster within 3 months prior to screening. e) History of tuberculosis (active or latent), irrespective of treatment status. f) A positive diagnostic tuberculosis 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 Purified Protein Derivative (PPD) testing. If the PPD reaction is less than (<) 5 millimeter (mm), then the participant is eligible. If the reaction is >= 5mm, or PPD testing is not undertaken, the participant is not eligible. g) 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 immunoglobulin A deficiency).
  • A major organ transplant (e.g. heart, lung, kidney, liver, pancreas) or hematopoietic 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.
  • A change in dose of oral sulfasalazine or aminosalicylate within 2 weeks prior to Baseline endoscopy.
  • Greater than 20 mg per day oral prednisolone (or equivalent), or a change in dose of corticosteroid within 2 weeks prior to Baseline endoscopy, or anticipated inability to maintain a stable dose of corticosteroids (<=20 mg oral prednisolone or equivalent) until Week 12.
  • Topical (rectal) corticosteroids or topical (rectal) aminosalicylate within 2 weeks prior to Baseline endoscopy.
  • Initiation or a change in dose of mercaptopurine or azathioprine (including initiation or discontinuation of allopurinol) or methotrexate within 8 weeks prior to Baseline endoscopy.
  • Treatment with ciclosporin, tacrolimus or thalidomide within 4 weeks prior to Baseline endoscopy.
  • Treatment with an anti-TNF biologic within 8 weeks prior to Baseline endoscopy, anti-integrin or anti-IL-12/23 biologics within 12 weeks prior to Baseline endoscopy, or a JAK inhibitor within 4 weeks prior to Baseline endoscopy.
  • A history of inadequate response, loss of response, or intolerance to more than three classes of approved advanced therapies for UC (including anti-TNF therapies, anti-integrin therapies, anti-IL-12/23 monoclonal antibodies, or JAK inhibitors; but excluding exposure within a clinical trial setting), of which participants must not have had inadequate response (primary non-response) to more than two classes.
  • Received fecal microbiota transplantation within 4 weeks prior to Baseline endoscopy.
  • Received live vaccination within 4 weeks of Day 1 or plan to receive during the study until Follow-Up.
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the screening endoscopy day in the current study:

    1. Biologics: 3 months, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer);
    2. New Chemical Entities (NCEs): 30 days, 5 half-lives, or twice the duration of the biological effect (whichever is longer).
  • Absolute neutrophil count <1.5 times 10^9 cells per liter (L) or a hemoglobin <80 grams per liter (g/L) or lymphocyte count <0.8 times 10^9 cells /L.
  • Estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) calculation <60 milliliter (mL) per minute per 1.73 m^2 at screening.
  • ALT >2 times upper limit of normal (ULN) and bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent) at screening.
  • Other clinically significant abnormalities of laboratory assessments, as judged by the investigator and/or GlaxoSmithKline Medical Monitor that could affect the safety of the participant, or the interpretation of the data from the study.
  • Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive hepatitis C antibody result at screening (Nota bene [NB]-Participants with Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid [RNA] test is obtained).
  • Positive serology for human immunodeficiency virus (HIV) at screening.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
  • QT interval corrected for heart rate (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with bundle branch block at screening and Day 1. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or over read.
  • Participants with hypersensitivity to GSK2831781 or any excipients in the clinical formulation of GSK2831781.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03893565


Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03893565    
Other Study ID Numbers: 204869
First Posted: March 28, 2019    Key Record Dates
Last Update Posted: September 15, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK2831781
Ulcerative colitis
Anti-LAG3 cell Depleting monoclonal antibody
Dose-response
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases