A multicentre randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety, tolerability, efficacy, dose-response, pharmacokinetics and pharmacodynamics of repeat dosing of an anti-LAG3 cell depleting monoclonal antibody (GSK2831781) in patients with active ulcerative colitis
- Conditions
- inflamatory bowel diseaseUlcerative colitis10017969
- Registration Number
- NL-OMON49796
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
AGE and WEIGHT:
1. 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:
2. Diagnosis of ulcerative colitis, established at least 3 months prior to
screening, as documented by diagnostic sigmoidoscopy or colonoscopy, and biopsy.
3. 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.
4. 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, loss of response to, intolerance to, or demonstrated
dependence on oral corticosteroids.
* 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.
5. 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
* 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:
6. Male and Female participants:
Both male and female participants are eligible to participate.
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 of the
protocol.
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
of the protocol.
INFORMED CONSENT:
7. Capable of giving signed informed consent as described in Section 10.1.3
10.1.3 of the protocol which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the protocol.
MEDICAL CONDITIONS:
1. Participants with a current diagnosis of indeterminate colitis, inflammatory
bowel disease-unclassified, Crohn*s disease, infectious colitis, or ischaemic
colitis.
2. 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.
3. Prior extensive colonic resection, subtotal or total colectomy, or
proctocolectomy, or planned surgery for UC.
4. 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.
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 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 Monitor*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.
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 (e.g. heart, lung, kidney, liver, pancreas) 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 carcin
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Numbers of participants with adverse events and serious adverse events up to<br /><br>Week 10.<br /><br>- Numbers of participants with findings of potential clinical importance up to<br /><br>Week 10 for: Vital signs, Clinical laboratory values (haematology, clinical<br /><br>chemistry and urinalysis), QTc.<br /><br>- Change from baseline in Complete Mayo score1 at Week 10.</p><br>
- Secondary Outcome Measures
Name Time Method