Study to Evaluate Safety, Tolerability and Efficacy of GSK2330811 in Crohn's Disease

The study will include participants with moderate to severe Crohn's disease. The aim is to evaluate the safety, tolerability, and efficacy of anti-oncostatin M monoclonal antibody (mAb) GSK2330811. This is a parallel group study with Induction and Maintenance periods. During Induction, the first 100 participants randomised will receive a 450mg GSK2330811 SC loading dose followed by 150mg weekly (Q1W), or placebo for 12 weeks. Additional dose-ranging arms will open after the 100th participant is randomized and in addition to placebo and the highest dose arms will also include a 300mg subcutaneous (SC) loading dose followed by 150mg SC every 2 weeks (Q2W) arm, a 300mg loading dose followed by 150mg SC every 4 weeks (Q4W) arm and a 150mg SC every 8 weeks (Q8W) arm. Participants with a clinical response at Week 12 will continue into a 40-week blinded maintenance period and will receive either 150mg SC Q2W, 150mg SC Q4W, 150mg SC Q8W or placebo. Participants without a clinical response at Week 12 will be offered up to 40 weeks of open label treatment with GSK2330811. Approximately 560 participants will be screened to randomize 280.


Eligibility Criteria:
Inclusion Criteria:

* Participant must be 18 years of age or over at the time of signing the informed consent.
* Participants who have a diagnosis of Crohn's Disease, established at least 3 months prior to first screening visit, supported by radiologic, histologic and/or endoscopic findings, and are expected to be able to be managed on an outpatient basis, if clinical course does not worsen.
* Participants who have active colitis and/or ileitis at screening, confirmed by centrally-read ileo-colonoscopy, defined as a baseline SES-CD score of \>= 7 (\>= 4 if disease confined to the terminal ileum) and \<=35.
* Participants who have active clinical disease at Baseline, measured by PRO2, defined as a 7-day average SF \>= 4 and/or a 7-day average AP \>=2.
* Participants who have a history of at least one of the following: Inadequate response to, loss of response to, or intolerance to conventional immunosuppression (i.e. azathioprine, 6-mercaptopurine, 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 biologic therapy or small molecule JAK inhibitors.
* Participants with Baseline body mass index (BMI) \>= 18.5 kilogram per square meter (kg/m\^2).
* Male and Female participants are both 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) or A WOCBP who agrees to use a contraceptive method that is highly effective, with a failure rate of \<1 percent, from 28 days prior to first dosing day (Day 1), during the dosing period and for at least 126 days (18 weeks) after the last dose of study treatment, corresponding to the time needed to eliminate any study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
* Participant who is capable of giving signed informed consent.

Exclusion Criteria:

* Participants with a current diagnosis of indeterminate colitis, inflammatory bowel disease (unclassified), infectious colitis, lymphocytic colitis, microscopic colitis, radiation colitis, ischemic colitis or ulcerative colitis.
* Participants with complications of Crohn's disease including strictures, adhesions, stenosis, short bowel syndrome and any other manifestation, if it is anticipated to require surgery during the study or that could interfere with study assessments (including but not limited to symptomatic strictures or stenosis) or that may confound the evaluation of benefit from treatment with GSK2330811.
* A current ileostomy or colostomy.
* Any bowel resection or diversion within 6 months or other intra-abdominal surgery within 3 months prior to the screening ileo-colonoscopy.
* Receiving tube feeding, defined formula diets, or total parenteral nutrition within 4 weeks prior to the screening ileo-colonoscopy.
* Current or prior abscess (proven or suspected) unless drained and adequately treated at least 3 weeks prior to the screening ileo-colonoscopy for cutaneous and perianal abscesses and at least 8 weeks prior to the screening ileo-colonoscopy for intra-abdominal abscesses. There must be no anticipated need for further surgery during the study.
* Active fistulas associated with an abscess and anticipated need for surgery during the study. If a fistula is present, it should have established drainage.
* Prior fecal micro-biota transplant within 3 months prior to the screening ileo-colonoscopy.
* Participants with any uncontrolled medical conditions, other than active Crohn's Disease, that in the opinion of the investigator puts the participant at unacceptable risk or likely will interfere with study assessments or data integrity. Other medical conditions should be stable at the time of screening expected to remain stable for the duration of the study.
* Known history of or current bleeding or coagulation disorder.
* Current or chronic history of liver or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones or uncomplicated fatty liver disease).
* A major organ transplant (example heart, lung, kidney, liver, pancreas) or hematopoietic stem cell/marrow transplant.
* Unstable lifestyle factors, such as alcohol use to excess or recreational drug use, to the extent that in the opinion of the investigator would interfere with the ability of a participant to complete the study.
* Major surgery within 3 months prior to the first screening visit or planned during the study.
* Cancer or carcinoma in situ present within the last 5 years, except for adequately treated non-metastatic basal or squamous cell cancers of the skin or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence.
* Active infection, or a history of infection as follows: Active or unresolved infection (i.e. bacterial, viral, fungal or parasitic). This does not include minor localized infections such as fungal nail infections, at the investigator's discretion; Infection requiring treatment with antimicrobials (i.e. antibacterial, antiviral, anti-parasitic or antifungal agents), where the last dose of antimicrobials falls within 4 weeks prior to the screening ileo-colonoscopy. This does not include topical antimicrobials, which are permitted; History of opportunistic infection (example Cytomegalovirus \[CMV\] colitis, disseminated herpes zoster), that has not resolved within 6 months prior to the screening ileo-colonoscopy or of recurrent infections, as determined by the investigator. This does not include infections that may occur in immunocompetent individuals, such as fungal nail infections or vaginal candidiasis, unless of an unusual severity or frequency.
* Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration \>5 millimeter \[mm\] at 48 to 72 hours, regardless of Bacillus Calmette-Guerin \[BCG\] or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test; Positive Clostridium difficile toxin test during screening. However, rescreening can be undertaken following documented successful treatment.
* Symptomatic herpes zoster within 3 months prior to the screening ileo-colonoscopy.
* Intravenous, intramuscular or rectal corticosteroids within 2 weeks prior to the screening ileo-colonoscopy.
* Oral corticosteroids at a dose greater than 20mg/day prednisolone (or equivalent) within 2 weeks prior to the screening ileo-colonoscopy. A dose \<= 20mg/day is permitted but this must have been at a stable dose for 2 weeks prior to the screening ileo-colonoscopy and participant and investigator assesses that the participant is likely able to maintain this stable dose until the Week 12 visit.
* Budesonide at a dose greater than 6mg/day within 2 weeks prior to the screening ileocolonoscopy. A dose \<= 6mg/day is permitted but this must have been at a stable dose for 2 weeks prior to the screening ileo-colonoscopy and participant and investigator should be willing to maintain this stable dose until the Week 12 visit.
* Any anti-Tumour necrosis factor (TNF) biologic within 8 weeks prior to screening ileo-colonoscopy and/or detectable blood levels within 8 weeks following last anti- TNF dose.
* Vedolizumab within 8 weeks prior to screening ileo-colonoscopy.
* Ustekinumab within 8 weeks prior to screening ileo-colonoscopy.
* Rituximab within 1 year prior to screening ileo-colonoscopy.
* Any previous treatment with alemtuzumab or natalizumab.
* Other biologic therapies/ or novel targeted therapies used for the treatment of Crohn's disease not mentioned in this section, unless approved by the Medical Monitor.
* Treatment with interferon, thalidomide, or methotrexate within 8 weeks prior to the screening ileo-colonoscopy, or treatment with methotrexate within 4 weeks prior to the screening ileo-colonoscopy.
* Treatment with azathioprine and 6-mercaptopurine unless on a stable dose for 8 weeks prior to the screening ileo-colonoscopy and participant and investigator should be willing to maintain this stable dose until the end of the follow-up period.
* Treatment with 5-aminosalicylates and sulfasalazine unless on a stable dose for 4 weeks prior to the screening ileo-colonoscopy and participant and investigator should be willing to maintain this stable dose until the end of the follow-up period.
* Live vaccine(s) within 4 weeks prior to the screening ileo-colonoscopy or plans to receive such vaccines during the study.
* Treatment with full dose anti-coagulant medications, including warfarin, heparin, thrombin inhibitors, and Factor Xa inhibitors within 2 weeks prior to the screening ileo-colonoscopy.
* Treatment with anti-platelet medications (example clopidogrel, prasugrel, ticagrelor and dipyridamole) within 2 weeks prior to the screening ileo-colonoscopy. This does not include aspirin at doses of 150 mg or less, or non-steroidal anti-inflammatory drugs, which are permitted.
* Receipt of an investigational product as part of participation in an interventional clinical trial within the following time period, prior to the Day 1 visit: 3 months, 5 half-lives, or twice the duration of the biological effect of the investigational product.
* Prior exposure to GSK2330811.
* Diagnostic assessments at screening: Hemoglobin \< 110 grams per Liter (g/L); Platelet count \< 150\*10\^9/L; Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment; Presence of the Hepatitis B core antibody (HBcAb) even if HBsAg is negative; Positive Hepatitis C antibody test result at screening or within 3 months prior first dose of study treatment; Positive Hepatitis C Ribonucleic acid (RNA) test results at screening or within 3 months prior to first dose of study treatment; Positive human immunodeficiency virus (HIV) antibody test; Estimated glomerular filtration rate Modification of Diet in Renal Disease (MDRD) calculation of \<45 milliliter (mL) per minute per 1.73m\^2; Alanine transferase (ALT) \> 2 times upper limit of normal (ULN); Bilirubin \> 1.5 times ULN (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
* QT corrected (QTc) \>450 millisecond (msec) or QTc \>480msec for participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF) or another method, either machine-read or manually over-read. The same correction formula should be used throughout the study.
* Where participation in the study would result in the donation of in excess of 500 mL blood over a 3-month period.
* Clinically significant multiple or severe drug allergies (including to humanized monoclonal antibodies), known hypersensitivity to GSK2330811 or any excipients used in the clinical formulation of GSK2330811, intolerance to topical corticosteroids, or a history of severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A \[IgA\] dermatosis, toxic epidermal necrolysis and exfoliative dermatitis).
* Any other history of significant allergy that in the opinion of the investigator contraindicates their participation in this study.
* Participants who, in the opinion of the investigator, would be unable to complete the daily diaries independently example unable to read and/or understand the questions being asked.