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-FR

Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

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, intolerance to, or demonstrated dependence on oral corticosteroids.
(3) Inadequate response to, loss of response to, or intolerance to one biologic class ONLY for the treatment of UC: either one or more anti-TNF therapies (e.g. infliximab, adalimumab, golimumab, or biosimilar) OR vedolizumab.
- Surveillance colonoscopy (performed according to local standards) within 12 months of screening (or during screening, if required) for participants with:
(1) Pancolitis of >8 years duration; or
(2) Patients with left-sided colitis of >12 years duration; or
(3) Patients with primary sclerosing cholangitis.
(4) For patients for whom this criterion does not apply, colorectal cancer surveillance should be undertaken according to local or national guidelines for patients with age =50, or with other known risk factors for colorectal cancer.

SEX
Female participants:
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
(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 280
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, Crohn's Disease, 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 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
(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 with the ability of a participant to complete the study
(6) An active infection or a history of serious infections as described fully in the protocol.
(7) Current or history of chronic liver or biliary disease (with the exception of Gilbert’s syndrome, asymptomatic gallstones or uncomplicated fatty liver disease)
(8) Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency (unless the participant has a documented history of selective 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 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

PRIOR/CONCOMITANT THERAPY:
(12) A change in dose of oral sulfasalazine or aminosalicylate within 2 weeks prior to baseline endoscopy
(13) Greater than 20mg/day oral prednisolone (or equivalent), or a change in dose of corticosteroid within 2 weeks prior to baseline endoscopy, or be unable to maintain a stable dose of corticosteroids (=20mg oral prednisolone or equivalent) until Week 12
(14) Topical (rectal) corticosteroids or topical (rectal) aminosalicylate within 2 weeks prior to baseline endoscopy
(15) 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
(16) Treatment with ciclosporin, tacrolimus or thalidomide within 4 weeks prior to baseline endoscopy
(17) Treatment with an anti-TNF biologic within 8 weeks prior to baseline endoscopy, or vedolizumab within 12 weeks prior to baseline endoscopy
(18) History of treatment with vedolizumab AND an anti-TNF biologic, regardless of treatment response (unless exposure to one or both drugs was only within a clinical trial setting)
(19) History of treatment with a monoclonal antibody therapy or targeted small molecule therapy for the treatment of UC not listed above
(20) Received live vaccination within 4 weeks 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 within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives, or twice the duration of the biological effect of the IP (whichev

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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