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A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3915393 in Participants With Celiac Disease (CeD)

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: NCT04604795
Recruitment Status : Recruiting
First Posted : October 27, 2020
Last Update Posted : February 8, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
Celiac disease is a common T cell-mediated disorder triggered by dietary gluten with a worldwide prevalence estimated at one percent. GSK3915393 is being developed as an orally administered inhibitor of the enzyme transglutaminase 2 (TG2) for the treatment of participants with CeD. This study is the first time into human study (FTIH) for GSK3915393.

Condition or disease Intervention/treatment Phase
Celiac Disease Drug: GSK3915393 Capsules Drug: GSK3915393 Solution for Infusion Drug: Placebo capsules Other: Gluten Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Part A is a crossover design, single-dose, dose escalation study where participants will be randomized to one of the 4 treatment sequences in 5 dosing periods. Part B is a parallel group, repeat oral dose, dose escalation study where participants will receive either GSK3915393 or matching placebo for 14 days in each cohort. Part C is a repeat oral dose study in CeD participants where they will receive GSK3915393 or matching placebo for 14 days.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double-blind study.
Primary Purpose: Treatment
Official Title: A Randomized, Placebo Controlled, Double Blind, Single and Repeat Dose Escalation Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK3915393 in Patients With Celiac Disease
Actual Study Start Date : November 4, 2020
Estimated Primary Completion Date : May 27, 2021
Estimated Study Completion Date : May 27, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
Experimental: Part A:GSK3915393 DLs 1,3,4,microdose and placebo (Sequence A)
In Part A, participants will receive dose levels (DLs) 1, 3, 4, microdose of GSK3915393, and placebo in a pre-determined sequence (Sequence A). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and pharmacokinetic data.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Drug: GSK3915393 Solution for Infusion
GSK3915393 solution for infusion will be administered intravenously.

Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part A:GSK3915393 DLs 1,2,4,microdose and placebo (Sequence B)
In Part A, participants will receive dose levels 1, 2, 4, microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence B). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and pharmacokinetic data.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Drug: GSK3915393 Solution for Infusion
GSK3915393 solution for infusion will be administered intravenously.

Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part A:GSK3915393 DLs 1,2,3,microdose and placebo (Sequence C)
In Part A, participants will receive dose levels 1, 2, 3, microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence C). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and pharmacokinetic data.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Drug: GSK3915393 Solution for Infusion
GSK3915393 solution for infusion will be administered intravenously.

Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part A:GSK3915393 DLs 2,3,4,microdose and placebo (Sequence D)
In Part A, participants will receive dose levels 2, 3, 4, microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence D). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and pharmacokinetic data.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Drug: GSK3915393 Solution for Infusion
GSK3915393 solution for infusion will be administered intravenously.

Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part B: Cohort 1: Participants receiving GSK3915393 DL X
Participants will receive GSK3915393 dose level X twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and pharmacokinetic data from Part A.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Placebo Comparator: Part B: Cohort 1: Participants receiving placebo
Participants will receive placebo matching GSK3915393 dose level X during Part B of the study.
Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part B: Cohort 2: Participants receiving GSK3915393 DL Y
Participants will receive GSK3915393 dose level Y twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and pharmacokinetic data from Part A and Part B.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Placebo Comparator: Part B: Cohort 2: Participants receiving placebo
Participants will receive placebo matching GSK3915393 dose level Y twice daily during Part B of the study
Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part B: Cohort 3: Participants receiving GSK3915393 DL Z
Participants will receive GSK3915393 dose level Z twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and pharmacokinetic data from Part A and Part B.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Placebo Comparator: Part B: Cohort 3: Participants receiving placebo
Participants will receive placebo matching GSK3915393 dose level Z twice daily during Part B of the study.
Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Experimental: Part C: CeD participants receiving GSK3915393
Participants with CeD will receive GSK3915393 twice daily during Part C of the study. Dose will be determined based on safety, tolerability and pharmacokinetic data. Participants will also receive gluten daily on Days 8 to 10.
Drug: GSK3915393 Capsules
GSK3915393 capsules will be given orally.

Other: Gluten
The gluten will be given orally as slices of bread or as gluten flour mixed with water.

Placebo Comparator: Part C: CeD participants receiving placebo
Participants with CeD will receive placebo matching GSK3915393 twice daily during Part C of the study. Participants will also receive gluten daily on Days 8 to 10.
Drug: Placebo capsules
Placebo matching GSK3915393 capsules will be given orally.

Other: Gluten
The gluten will be given orally as slices of bread or as gluten flour mixed with water.




Primary Outcome Measures :
  1. Part A: Number of participants with adverse events (AEs), serious AEs (SAEs), and treatment related AEs following oral dosing [ Time Frame: Up to Week 11 ]
    AEs, SAEs and treatment related AEs will be collected.

  2. Part B: Number of participants with AEs, SAEs and treatment related AEs [ Time Frame: Up to Week 4 ]
    AEs, SAEs and treatment related AEs will be collected.

  3. Part C: Number of participants with AEs, SAEs and treatment related AEs [ Time Frame: Up to Week 4 ]
    AEs, SAEs and treatment related AEs will be collected.

  4. Part A: Number of participants with clinically significant changes in physical examination following oral dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in physical examination will be assessed.

  5. Part B: Number of participants with clinically significant changes in physical examination [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in physical examination will be assessed.

  6. Part C: Number of participants with clinically significant changes in physical examination [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in physical examination will be assessed.

  7. Part A: Number of participants with clinically significant changes in vital signs following oral dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in vital signs will be assessed.

  8. Part B: Number of participants with clinically significant changes in vital signs [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in vital signs will be assessed.

  9. Part C: Number of participants with clinically significant changes in vital signs [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in vital signs will be assessed.

  10. Part A: Number of participants with clinically significant changes in hematology parameters following oral dosing [ Time Frame: Up to Week 11 ]
    Blood samples will be collected for the assessment of hematology parameters.

  11. Part B: Number of participants with clinically significant changes in hematology parameters [ Time Frame: Up to Week 4 ]
    Blood samples will be collected for the assessment of hematology parameters.

  12. Part C: Number of participants with clinically significant changes in hematology parameters [ Time Frame: Up to Week 4 ]
    Blood samples will be collected for the assessment of hematology parameters.

  13. Part A: Number of participants with clinically significant changes in clinical chemistry parameters following oral dosing [ Time Frame: Up to Week 11 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  14. Part B: Number of participants with clinically significant changes in clinical chemistry parameters [ Time Frame: Up to Week 4 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  15. Part C: Number of participants with clinically significant changes in clinical chemistry parameters [ Time Frame: Up to Week 4 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  16. Part A: Number of participants with clinically significant changes in urinalysis parameters following oral dosing [ Time Frame: Up to Week 11 ]
    Urine samples will be collected for the assessment of urinalysis parameters.

  17. Part B: Number of participants with clinically significant changes in urinalysis parameters [ Time Frame: Up to Week 4 ]
    Urine samples will be collected for the assessment of urinalysis parameters

  18. Part C: Number of participants with clinically significant changes in urinalysis parameters [ Time Frame: Up to Week 4 ]
    Urine samples will be collected for the assessment of urinalysis parameters.

  19. Part A: Number of participants with clinically significant changes in electrocardiogram findings following oral dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in electrocardiogram findings will be assessed.

  20. Part B: Number of participants with clinically significant changes in electrocardiogram findings [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in electrocardiogram findings will be assessed.

  21. Part C: Number of participants with clinically significant changes in electrocardiogram findings [ Time Frame: Up to Week 4 ]
    Participants with clinically significant changes in electrocardiogram findings will be assessed.


Secondary Outcome Measures :
  1. Part A: Maximum observed plasma drug concentration (Cmax) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  2. Part A: Cmax following single intravenous (IV) dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  3. Part A: Time to maximum observed plasma concentration (Tmax) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  4. Part A: Tmax following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  5. Part A: Area under the plasma concentration time curve from time zero to last quantifiable concentration (AUC[0 to t]) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  6. Part A: AUC(0 to t) following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  7. Part A: AUC from time zero to infinity (AUC[0 to inf]) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  8. Part A: AUC(0 to inf) following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  9. Part A: Apparent terminal phase half-life (T1/2) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  10. Part A: T1/2 following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  11. Part A: Clearance (CL) following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  12. Part A: Volume of distribution (Vd) following single IV dose of GSK3915393 [ Time Frame: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  13. Part A: Absolute bioavailability (F) following single oral dose of GSK3915393 [ Time Frame: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days) ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  14. Part A: Number of participants with AEs, SAEs and treatment related AEs following IV dosing [ Time Frame: Up to Week 11 ]
    AEs, SAEs and treatment related AEs will be collected.

  15. Part A: Number of participants with clinically significant changes in physical examination following IV dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in physical examination will be assessed.

  16. Part A: Number of participants with clinically significant changes in vital signs following IV dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in vital signs will be assessed.

  17. Part A: Number of participants with clinically significant changes in hematology parameters following IV dosing [ Time Frame: Up to Week 11 ]
    Blood samples will be collected for the assessment of hematology parameters.

  18. Part A: Number of participants with clinically significant changes in clinical chemistry parameters following IV dosing [ Time Frame: Up to Week 11 ]
    Blood samples will be collected for the assessment of clinical chemistry parameters.

  19. Part A: Number of participants with clinically significant changes in urinalysis parameters following IV dosing [ Time Frame: Up to Week 11 ]
    Urine samples will be collected for the assessment of urinalysis parameters.

  20. Part A: Number of participants with clinically significant changes in electrocardiogram findings following IV dosing [ Time Frame: Up to Week 11 ]
    Participants with clinically significant changes in electrocardiogram findings will be assessed.

  21. Part B: Cmax following first dose of GSK3915393 [ Time Frame: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  22. Part B: Cmax following second dose of GSK3915393 [ Time Frame: 10 hours to 24 hours post first dose on Days 1 and 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  23. Part B: Tmax following first dose of GSK3915393 [ Time Frame: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  24. Part B: Tmax following second dose of GSK3915393 [ Time Frame: 10 hours to 24 hours post first dose on Days 1 and 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  25. Part B: AUC(0-t) following first dose of GSK3915393 [ Time Frame: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  26. Part B: AUC(0-t) following second dose of GSK3915393 [ Time Frame: 10 hours to 24 hours post first dose on Days 1 and 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  27. Part B: AUC over the dosing interval (AUC[0 to tau]) following first dose of GSK3915393 [ Time Frame: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  28. Part B:AUC(0 to tau) following second dose of GSK3915393 [ Time Frame: 10 hours to 24 hours post first dose on Days 1 and 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393

  29. Part B: Trough concentration (Ctrough) following repeat dose of GSK3915393 [ Time Frame: Pre first dose on Days 2, 3, 5, 7, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  30. Part C: Cmax following single dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Day 1 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  31. Part C: Tmax following single dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Day 1 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  32. Part C: AUC(0-t) following single dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Day 1 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  33. Part C: AUC(0-inf) following single dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Day 1 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  34. Part C: T1/2 following single dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Day 1 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  35. Part C: Cmax following repeat dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Days 7, 8, 10, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  36. Part C: Tmax following repeat dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Days 7, 8, 10, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  37. Part C: AUC(0-t) following repeat dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Days 7, 8, 10, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  38. Part C: AUC(0-tau) following repeat dose of GSK3915393 [ Time Frame: Pre-dose to 10 hours post first dose on Days 7, 8, 10, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  39. Part C: Ctrough following repeat dose of GSK3915393 [ Time Frame: Pre first dose on Days 2, 7, 8, 10, 14 ]
    Blood samples will be collected at the indicated time points for pharmacokinetic analysis of GSK3915393.

  40. Part C: Maximum pre to post gluten challenge changes in Interleukin-2 (IL-2) on Day 8 [ Time Frame: Immediately pre-dose and up to 6 hours post gluten ingestion on Day 8 ]
    Blood samples will be collected at indicated time points for assessment of IL-2. It is the maximum change in IL2 from pre to post gluten challenge on Day 8.



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 to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For Healthy Participants (Parts A and B):

  • Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  • Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Negative coronavirus disease of 2019 (COVID-19) test for inclusion: Two consecutive approved molecular tests (Polymerase chain reaction [PCR] or antigen test) separated by >24 hours. At Screening or within 48 hours prior to start of Screening AND the second test ideally should be within 72 hours prior to admission to the unit. While awaiting test results participants should follow precautions as advised by the clinical unit.
  • Body weight >=40 kilograms (kg) and body mass index (BMI) within the range 18.5-29.9 kilogram per square meter (kg/m^2) (inclusive).
  • Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent. For Participants with CeD (Part C)
  • Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
  • Participants with CeD who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Participants with a diagnosis of CeD: Documented diagnosis of CeD >=6 months before study entry, based on American College of Gastroenterology 2013 guideline on CeD diagnosis and management. The confirmation of a diagnosis of CeD should be based on serology and upper endoscopy with histological analysis of a biopsy of the duodenum. A positive biopsy consistent with CeD. Every effort should be made to obtain the biopsy report to support the diagnosis of CeD. Prospective participants should not undergo biopsy for the sole purpose for participating in this trial. Participants for whom the biopsy report is not available may be enrolled in the study only after consultation with the GlaxoSmithKline Medical Monitor AND a positive gluten-specific serology to tissue transglutaminase (tTG) or endomysial antibodies (EMA), and/or gliadin-derived peptides (DGP). Every effort should be made to obtain the serology report. Participants for whom the serology report is not available may be enrolled in the study only if they have a report of duodenal biopsy confirming CeD. Participants with CeD must have been following a gluten-free diet for >= 6 months before study entry and be in remission defined as absence of symptoms typical of CeD for at least 2 months prior to the study and Immunoglobulin A (IgA) antibodies to tTG within normal limits at screening. Participants with weakly positive IgA antibodies to tTG may be included following discussion with the GlaxoSmithKline Medical Monitor; Human leukocyte antigen DQ (HLA-DQ) typing associated with CeD; No clinically significant abnormal laboratory test results other than those related to CeD as determined by the investigator.
  • Negative COVID-19 test for inclusion: Two consecutive approved molecular tests (PCR or antigen test) separated by >24 hours. At Screening or within 48 hours prior to start of Screening AND the second test ideally should be within 72 hours prior to admission to the unit. While awaiting test results participants should follow precautions as advised by the clinical unit.
  • Body weight >=40 kg and body mass index (BMI) within the range 18.5-29.9 kg/m^2 (inclusive).
  • Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a WONCBP OR Is a WOCBP and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • Capable of giving signed informed consent.

Exclusion Criteria:

For Healthy Participants (Parts A and B):

  • History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • Current evidence of active infection.
  • Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
  • Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
  • Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant's lifetime.
  • Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of gastrointestinal (GI) surgery (with exception of appendectomy).
  • Average QT interval corrected using Bazett's formula (QTcF) >450 milliseconds (msec) at screening.
  • Any clinically relevant abnormality on the screening medical assessment, laboratory examination, or electrocardiogram.
  • History of QTc prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
  • History of sensitivity to any of the study medication, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
  • Use of any immunosuppressive medications within 6 months prior to entry.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including Saint [St] John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication for each dosing, unless in the opinion of the Investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. (Paracetamol is acceptable at a dose of no more than 500 milligrams [mg] at a time and no more than 2 grams [g] per day).
  • Recent donation of blood or blood products such that participation in the study would result in loss of blood in excess of 500 milliliter (mL) within 56 days.
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
  • Unwillingness or inability to follow the procedures outlined in the protocol or any other type of medical research within 30 days of randomization.
  • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
  • Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
  • A positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
  • Regular alcohol consumption within 6 months prior to screening: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or use of tobacco or nicotine-containing products (e.g. nicotine patches or vaporizing devices) at screening or on admission to the unit.

For Participants with CeD (Part C):

  • History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological, or psychiatric disorders, capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data; With the exception of CeD AND History of IBS and GERD in the past. Participants with active, current symptoms of IBS or GERD are not eligible.
  • Current evidence of active infection.
  • Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
  • Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
  • Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant's lifetime.
  • ALT >1.5 times ULN.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of GI surgery (with exception of appendectomy).
  • History of food allergy or food intolerance other than to gluten and lactose.
  • Average QTcF >450 msec at screening.
  • Any clinically relevant abnormality on the screening medical assessment, laboratory examination, or electrocardiogram.
  • History of QTc prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
  • History of sensitivity to any of the study medication, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
  • Use of any immunosuppressive medications within 6 months prior to entry or systemic corticosteroids within 3 months prior to entry.
  • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication for each dosing, unless in the opinion of the Investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. (Paracetamol is acceptable at a dose of no more than 500 mg at a time and no more than 2 g per day).
  • Recent donation of blood or blood products such that participation in the study would result in loss of blood in excess of 500 mL within 56 days.
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
  • Unwillingness or inability to follow the procedures outlined in the protocol or any other type of medical research within 30 days of randomization.
  • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
  • Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
  • A positive pre-study drug/alcohol screen.
  • Positive HIV antibody test.
  • History of drug abuse (as defined by the current version of the DSM) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
  • Regular alcohol consumption within 6 months prior to screening defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urinary cotinine levels indicative of smoking or use of tobacco or nicotine-containing products (e.g. nicotine patches or vaporizing devices) at screening or on admission to the unit.

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): NCT04604795


Contacts
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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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United Kingdom
GSK Investigational Site Recruiting
London, United Kingdom, NW10 7EW
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Malcolm Boyce         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04604795    
Other Study ID Numbers: 213585
First Posted: October 27, 2020    Key Record Dates
Last Update Posted: February 8, 2021
Last Verified: February 2021
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: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Celiac disease
Gluten challenge
GSK3915393
Healthy Participants
Pharmacokinetics
Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases