Safety, tolerability, efficacy and dose-response of GSK2831781 in ulcerative colitis.

Phase 1

Conditions: lcerative Colitis
MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2018-003278-28-BG

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 320

Inclusion Criteria

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:
(1) 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.
(2) Inadequate response to, loss of response to, intolerance to, or demonstrated dependence on oral corticosteroids.
(3) Inadequate response to, loss of response to, or intolerance to at least one approved advanced therapy for UC, including anti-TNF therapies, anti-integrin therapies, anti-IL-12/23 monoclonal antibodies or JAK inhibitors.
- Surveillance colonoscopy (performed according to local standards) within 12 months of screening (or during screening, if required) for participants with:
(1) Pancolitis of >8 years duration; or
(2) Patients with left-sided colitis of >12 years duration; or
(3) 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
Both male and female participants are eligible to participate.
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:
(1) Not a woman of childbearing potential (WOCBP),
OR
(2) A WOCBP who agrees to use a highly effective contraceptive method for at least 4 weeks prior to dosing, until the Follow-Up visit.

INFORMED CONSENT
-Capable of giving signed informed consent as described in the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 202
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

Medical Conditions:
1)Current diagnosis of indeterminate colitis, inflammatory bowel disease-unclassified, CD, infectious colitis, or ischaemic colitis
2)Fulminant UC (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
3)Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC
4)Any uncontrolled medical conditions, other than active UC, that in the opinion of the investigator put the participant at unacceptable risk or interfere w/ 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
5)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 w/ the ability of a participant to complete the study
6)An active infection or a history of serious infections as described in the protocol
7)Current or history of chronic liver or biliary disease w/ the exception of Gilbert’s syndrome, asymptomatic gallstones or uncomplicated fatty liver disease
8)Hereditary/acquired immunodeficiency disorder, including immunoglobulin deficiency unless the participant has a documented history of elective IgA deficiency
9)A major organ transplant or haematopoietic stem cell/marrow transplant
10)Any planned major surgical procedure during the study
11)A history of malignant neoplasm w/in the last 5 yrs, except for adequately treated non-metastatic basal or squamous cell cancers of the skin (w/in 1 yr) or carcinoma in situ of the uterine cervix (w/in 3 yrs) that has been fully treated and shows no evidence of recurrence
PRIOR/CONCOMITANT THERAPY:
12)A change in dose of oral sulfasalazine or aminosalicylate w/in 2 wks prior to baseline endoscopy
13)=20mg/day oral prednisolone, or a change in dose of corticosteroid w/in 2 wks prior to baseline endoscopy, or anticipated inability to maintain a stable dose of corticosteroids (=20 mg oral prednisolone or equivalent) until Wk12
14)Topical(rectal) corticosteroids or topical(rectal) aminosalicylate w/in 2 wks prior to baseline endoscopy
15)Initiation/change in dose of mercaptopurine or azathioprine (including initiation/discontinuation of allopurinol) or methotrexate w/in 8 wks prior to baseline endoscopy
16)Treatment w/ ciclosporin, tacrolimus or thalidomide w/in 4 wks prior to baseline endoscopy
17)Treatment w/ an anti-TNF biologic w/in 8 wks prior to baseline endoscopy, anti-integrin or anti-IL-12/23 biologics w/in 12 wks prior to baseline endoscopy, or a JAK inhibitor w/in 4 wks prior to baseline endoscopy
18)History of inadequate response, loss of response, or intolerance to more than 3 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 w/in a clinical trial setting), of which participants must not have had inadequate response to more than 2 classes
19)Received faecal microbiota transplantation w/in 4 wks prior to baseline endoscopy
20 Received live vaccination w/in 4 wks of Day 1 or plan to receive during the study until Follow-Up
PRIOR/CONCURRENT CLINICAL STUDY EXPERIENCE:
21)Participated in a clinical trial and received an IP w/in the following time period prior to this study’s screening endoscopy day: Biologics: 3 mths

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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