GSK2982772 Study in Subjects With Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02903966
• Date of registration: 13/09/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: GSK2982772 Study in Subjects With Ulcerative Colitis
• Scientific title: A Multicentre, Randomised, Double-blind (Sponsor Unblinded), Placebo-controlled Study With Open Label Extension to Investigate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of GSK2982772 in Subjects With Active Ulcerative Colitis
• Date of first enrolment: November 15, 2016
• Target sample size: 36
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02903966
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany, Netherlands, Poland, Russian Federation, Sweden, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Between 18 and 75 years of age inclusive, at the time of signing the informed consent.

- Subjects that do not have any medical conditions, other than active UC, that in the
opinion of the Investigator put the subject at unacceptable risk or interfere with
study assessments or integrity of the data. These medical conditions should be stable
at the time of screening and are expected to remain stable for the duration of the
study.

- Subject has had a confirmed diagnosis of active UC, as documented by complete
diagnostic colonoscopy to the terminal ileum (TI) with biopsy performed >=3 months
prior to screening. If diagnostic colonoscopy was not performed to the TI, it must be
documented by the principal investigator that the subject has diffuse inflammation
from the rectum extending proximally to the colon in a continuous and uniform way.

- A Complete Mayo Score of >=3 points and endoscopy sub score of 2 to 3 at screening,
despite concurrent treatment with at least 1 of the following (oral corticosteroids or
any oral 5-aminosalicylates (5-ASA) or purine analogues or all as defined): Oral 5-ASA
at a stable dose (equivalent to >=2.4 grams per day (g/day) of Asacol) for at least 4
weeks prior to first dose. Must remain on a stable dose until end of treatment; Purine
analogues (azathioprine, mercaptopurine, thiopurines) or methotrexate for at least 12
weeks prior to first dose. Must remain on a stable dose until end of treatment; Stable
low dose oral corticosteroid (up to 20 mg prednisolone or equivalent) for 2 weeks
prior to sigmoidoscopy. Must remain on a stable dose until end of treatment.

- If on rectal 5-ASA or corticosteroids, must remain on a stable dose for at least 4
weeks prior to first dose. Must remain on stable dose until the end of treatment.

- Subject is naive to any biological therapies for UC OR Subject may have had previous
exposure to a single anti-tumor necrosis factor (TNF) biologic agent which was
discontinued for reasons other than primary non-response more than 8 weeks (or 5
half-lives whichever is longer) prior to first dose OR Subject may have had previous
exposure to a single biologic agent (example, vedolizumab) in the context of a
previous clinical trial. The biologic agent must have been discontinued more than 8
weeks (or 5 half-lives whichever is longer) prior to first dose. Note: Exposure to a
single biologic agent is not required in addition to inclusion criteria listed above
(number fourth and fifth on the list).

- A body mass index (BMI) within range of 18.5 to 35 kilogram per meter square (kg/m^2)
(inclusive) at screening.

- Male and Female subjects:

Males: Male subjects with female partners of child bearing potential must comply with the
contraception requirements.

Females: A female subject is eligible to participate if she is not pregnant (as confirmed
by a negative serum human chorionic gonadotrophin (hCG) test), not lactating, and at least
one of the following conditions applies:

Non-reproductive potential defined as 1) Pre-menopausal females with one of the following:
Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with
follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral
Oophorectomy. 2) Postmenopausal defined as 12 months of spontaneous amenorrhea in
questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and
estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT)
and whose menopausal status is in doubt will be required to use one of the highly effective
contraception methods if they wish to continue their HRT during the study. Otherwise, they
must discontinue HRT to allow confirmation of post-menopausal status prior to study
enrolment.

Reproductive potential and agrees to follow one of the options listed in the Modified List
of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential
(FRP) from 30 days prior to the first dose of study medication and until at least 2 days
after the last dose of study medication and completion of the follow-up visit. The
Investigator is responsible for ensuring that subjects understand how to properly use
methods of contraception.

- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the consent form and protocol.

Exclusion Criteria:

- Subject with diagnosis of indeterminate colitis, Crohn's Disease, infectious colitis,
or ischemic colitis.

- Subject with fulminant UC, or UC limited to the rectum (disease extent <15 centimeters
(cm) from the anal verge).

- Subject with previous small bowel or colonic surgery(with exception of appendectomy),
histological evidence of colonic dysplasia or bowel stricture.

- Subject with colostomy, fistulae or known symptomatic stenosis of the intestine.

- Subject with toxic megacolon.

- Subject with positive Clostridium difficile toxin test or active/previous colonic
cytomegalo virus (CMV) infection.

- Subject with current history of suicidal ideation behavior (SIB) as measures using the
Columbia Suicide Severity Rating Scale (C-SSRS) or history of attempted suicide.

- An active infection, or a history of infections as follows:

Hospitalization for treatment of infection within 60 days before first dose (Day 1).

Currently on any suppressive therapy for a chronic infection (such as pneumocystis,
cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).

Use of parenteral (intravenous (IV) or intramuscular) antibiotics (antibacterials,
antivirals, antifungals, or antiparasitic agents) for an infection within 60 days before
first dose.

A history of opportunistic infections within 1 year of screening (example: pneumocystis
jirovecii, CMV pnemonitis, aspergillosis). 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.

History of tuberculosis (TB), irrespective of treatment status. A positive diagnostic TB
test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases
where the QuantiFERON or T-spot test is indeterminate, the subject may have the test
repeated once, but they will not be eligible for the study unless the second test is
negative. In cases where the QuantiFERON or T-spot test


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: Placebo

Drug: GSK2982772

Primary Outcome(s)

Part A: Number of Participants With Worst Case Abnormal Clinical Chemistry Parameters by Potential Clinical Importance (PCI) Criteria [Time Frame: Up to Day 43]

Part A: Number of Participants With Common (>=5%) Non-serious Adverse Events (Non-SAEs) and Any Serious Adverse Events (SAEs) [Time Frame: Up to Day 43]

Part B: Number of Participants With Worst Case Abnormal HR Results by PCI Criteria [Time Frame: From Day 44 to Day 112]

Part A: Number of Participants With Worst Case Abnormal Heart Rate (HR) Results by PCI Criteria [Time Frame: Up to Day 43]

Part B: Number of Participants With Worst Case Abnormal Blood Pressure Results by PCI Criteria [Time Frame: From Day 44 to Day 112]

Part B: Number of Participants With Worst Case Abnormal Hematology Parameters by PCI Criteria [Time Frame: From Day 44 to Day 112]

Part A: Number of Participants With Worst Case Abnormal Hematology Parameters by PCI Criteria [Time Frame: Up to Day 43]

Part A: Number of Participants With Worst Case Abnormal Urinalysis Results by Dipstick Method [Time Frame: Up to Day 43]

Part A: Number of Participants With Worst-case Abnormal Electrocardiogram (ECG) Findings [Time Frame: Up to Day 43]

Part B: Number of Participants With Worst Case Abnormal Clinical Chemistry Parameters by Potential Clinical Importance (PCI) Criteria [Time Frame: From Day 44 to Day 112]

Part A: Number of Participants With Worst Case Abnormal Blood Pressure Results by PCI Criteria [Time Frame: Up to Day 43]

Part B: Number of Participants With Worst-case Abnormal ECG Findings [Time Frame: From Day 44 to Day 112]

Part B: Number of Participants With Worst Case Abnormal Urinalysis Results by Dipstick Method [Time Frame: From Day 44 to Day 112]

Part B: Number of Participants With Common (>=5%) Non Serious AEs and SAEs [Time Frame: From Day 44 to Day 112]

Secondary Outcome(s)

Part A: Change From Baseline in Fecal Calprotectin (FCP) [Time Frame: Baseline (Day 1, pre-dose) and Days 15, 29, 43]

Part A: Change From Baseline in Modified Riley Scale Score (MRS) [Time Frame: Baseline (Day 1, pre-dose) and Day 43]

Part B: Change From Baseline in MRS Score [Time Frame: Baseline (Day 1, pre-dose) and Day 85]

Part B: Percentage of Participants Who Achieved an Absolute Mayo Endoscopy Subscore of 0 or 1 at Day 85 [Time Frame: Day 85]

Part A: Pre-dose Plasma Concentration of GSK2982772 [Time Frame: Day 43]

Part B: Change From Baseline in Geboes Index Total Score [Time Frame: Baseline and Day 85]

Part A: Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Total Score [Time Frame: Baseline (screening - within 30 days prior to Day 1) and Day 43]

Part A: Change From Baseline in Mean C Reactive Protein (CRP) [Time Frame: Baseline (Day 1, pre-dose) and Days 15, 29, 43]

Part A: Change From Baseline in Partial Mayo Score [Time Frame: Baseline (Screening - within 30 days prior to Day 1) and at Days 15, 29, 43]

Part B: Number of Participants Who Achieved Mayo Clinical Response [Time Frame: Day 85]

Part B:Change From Baseline in FCP [Time Frame: Baseline (Day 1, pre-dose) and Days 57, 71, 85]

Part A: Number of Participants Who Achieved Mayo Clinical Remission [Time Frame: Day 43]

Part B: Number of Participants Who Achieved Mayo Clinical Remission [Time Frame: Day 85]

Part B:Change From Baseline in Mean CRP [Time Frame: Baseline (Day 1, pre-dose) and Days 57, 71, 85]

Part A: Change From Baseline in Geboes Index Total Score [Time Frame: Baseline and Day 43]

Part A: Number of Participants Who Achieved Mayo Clinical Response [Time Frame: Day 43]

Part A: Percentage of Participants Who Achieved an Absolute Mayo Endoscopy Subscore of 0 or 1 at Day 43 [Time Frame: Day 43]

Part B: Change From Baseline in Partial Mayo Score [Time Frame: Baseline and Day 85]

Part B: Change From Baseline in Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Total Score [Time Frame: Baseline (screening - within 30 days prior to Day 1) and Day 85]

Part B: Trough Concentrations of GSK2982772 on Day 85 [Time Frame: Day 85]

Part A: Post-dose Plasma Concentrations of GSK2982772 [Time Frame: Days 1 and 43: 1, 2, 4 and 6 hours post dose]

Secondary ID(s)

202152

2016-001833-29

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/06/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02903966