Health Condition 1: K518- Other ulcerative colitis
Conditions
Interventions
Intervention1: Biological: GSK2831781: Subjects will receive different doses of GSK2831781 during Induction and Maintenance Phase
Control Intervention1: Drug: Placebo: Commercial saline solution will
Sponsors
GlaxoSmithKline Research Development Limited
Eligibility
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all the following criteria apply 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: 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, intolerance to, or demonstrated dependence on oral corticosteroids. 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: Pancolitis of >8 years duration; or Patients with left-sided colitis of >12 years duration; or Patients with primary sclerosing cholangitis. 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: Not a woman of childbearing potential (WOCBP), see Section 10.4.1, WOCBP definitions. OR A WOCBP who agrees to use a highly effective contraceptive method for at least 4 weeks prior to dosing, until the Follow-Up visit. See Section 10.4.2, Contraceptive Guidance. INFORMED CONSENT Capable of giving signed informed consent as described in Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
Exclusion criteria: Participants with a current diagnosis of indeterminate colitis, inflammatory bowel disease-unclassified, Crohnâ??s disease, infectious colitis, or ischaemic colitis. Participants with fulminant ulcerative colitis (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. Prior extensive colonic resection, subtotal or total colectomy, or proctocolectomy, or planned surgery for UC. Participants with 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. 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: - 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 Monitorâ??s discretion). - A history of opportunistic infections within 1 year of screening (e.g. Pneumocystis jirovecii, aspergillosis or CMV 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. - 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. - Symptomatic herpes zoster within 3 months prior to screening. - History of tuberculosis (active or latent), irrespective of treatment status. - A positive diagnostic TB 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 PPD testing. If the PPD reaction is participant is eligible. If the reaction is >=5 mm, or PPD testing is not undertaken, the participant is not eligible. - 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 Gilbertâ??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 IgA deficiency). A major organ transplant (e.g. heart, lung, kidney, liver, pancreas) or haematopoietic 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 tr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective - To evaluate the safety and tolerability of repeat doses of GSK2831781 - To characterise the efficacy dose response of GSK2831781 during the Induction Phase. Timepoint: Week 10 | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of participants who achieve -Mayo endo score of 0 or 1 at Wk 10 -Mayo clinical remission at Wk 10 Change from baseline in -partial Mayo score over time -Mayo endo score & UCEIS at Wk 10 -histological severity at Wk 10 as determined by Robarts Histopathology Index Nancy Histological Index Geboes Score -Serum C reactive protein over time -faecal calprotectin over time Timepoint: Week 10 mayo score and end of study safety endpoints;To investigate the - Effect of repeat doses of GSK2831781 on clinical efficacy including endoscopic mucosal healing during the Induction Phase - Effect of repeat doses of GSK2831781 on UC histologic disease activity during the Induction Phase - Effect of repeat doses of GSK2831781 on biomarkers of UC disease activity during the Induction Phase - Pharmacokinetics of GSK2831781 following repeat intravenous and subcutaneous dosing - Immunogenicity of repeat doses of GSK2831781Timepoint: Week 10 (mayo score) and end of study (safety endpoints) | — |
Countries
Belgium, Bulgaria, Canada, Czech Republic, Estonia, France, Hungary, India, Japan, Mexico, Netherlands, Poland, Republic of Korea, Russian Federation, Serbia, Slovakia, South Africa, Ukraine, United Kingdom, United States of America
Contacts
Public ContactVanaja Krishnan
George Clinical India Private Limited
Outcome results
None listed