Safety, Tolerability, Efficacy and Dose-response of GSK2831781 in Ulcerative Colitis
- Conditions
- Health Condition 1: K518- Other ulcerative colitis
- Registration Number
- CTRI/2020/03/023899
- Lead Sponsor
- GlaxoSmithKline Research Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
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.
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 <5 mm, then the
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method