Intervention: Hdac-IN-3
Trial phase: Phase 2
SMILES: O=C(CCc1ccc(CNC(C(=O)OC2CCCC2)C2CCCCC2)cn1)NO
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1
Group description: Eligible participants in this arm, received a dose of 40 mg of GSK3117391, administered orally once a day as 2 capsules of 20 mg each in the morning, following every other day, for 28-days.
Eligibility criteria:
Inclusion Criteria:

Age >=18 years at the time of signing the informed consent.
The subject must have a diagnosis of RA according to the 2010 ACR/ European League Against Rheumatism (EULAR) classification criteria for RA.
Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA
The subject must have a EULAR DAS 28-CRP of greater than 5.1 at screening.
Disease duration of >6 months (time from onset of patient-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists).
Swollen joint count of >=6 (66-joint count) and tender joint count of >=8 (68-joint count) at screening and at day 1
The subject must have a CRP serum level of >=5 mg/L at screening
The subject has had an inadequate response or intolerance of DMARDs (due to lack of efficacy or toxicity, after at least 8 weeks treatment).
Body weight >=45 kilograms (kg) and body mass index (BMI) within the 18.5 - 35 kg/square metre (m^2) inclusive.
Male or female requirements. Males: Male subjects with female partners of child bearing potential must comply with contraception requirements from the time of first dose of study medication 91 days after the last dose of study medication. In addition, male subjects must not donate sperm for 91 days after the last dose of study medication.

Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:

Non-reproductive potential defined as pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea.

Females of reproductive potential must have proper and established use of a Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 28 days prior to the first dose of study medication and until 15 weeks after the last dose of study medication and completion of the follow-up visit. In addition, subjects will be required to utilise a barrier method of contraception. A negative HCG pregnancy test, (serum at screening visit and urine for subsequent visits) with a sensitivity of at least 25 international units per litre [IU/L]) is required at the screening visit, between Day -7 to -4 and on Day 1 prior to dose administration. Further pregnancy tests are required at the weekly study visits and the follow-up visit.

Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Exclusion Criteria:

Pregnant or lactating women.
Subjects who meet diagnostic criteria for any other rheumatic disease (example [eg], lupus erythematosus, gout, psoriatic arthritis).
Subjects who have previously been treated with more than 1 biologic agent (such as TNF inhibitors eg. adalimumab, etanercept, infliximab, certolizumab, golimumab or non-TNF inhibitors eg. abatacept, rituximab, tociluzimab) or any investigational biologic.
Subjects with past history of granulomatous disease eg. leprosy, sarcoidosis.
Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, haematological (including clotting disorders), gastrointestinal (including gastrooesophageal ulcers), pulmonary, cardiac (including ischemic heart disease), neurological, or cerebral disease, or other medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study.
Subjects with any values for monocytes are below the lower limit of normal (LLN) at screening.
Haemoglobin <11 grams (g)/decilitre (dL); haematocrit <30%, white blood cell count <=3,000/cubic millimeter (mm^3) (<=3.0 x 10^9/litre [L]) or >=14,000/mm^3 (>=14 x 10^9/L); platelet count <= 100,000/microlitre (μL) (<=100x10^9/L); absolute neutrophil count <=2x10^9/L; lymphocyte count <1x10^9/L at screening.
Alanine transaminase (ALT) and bilirubin >1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Corrected QT interval (QTc) by Fridericia's correction formula (QTcF) or QTc by Bazett's correction formula (QTcB) >450 milliseconds (msec) (based on the average of triplicate electrocardiograms [ECGs]) at screening.
Abnormal findings on ECG considered clinically significant by the investigator.
A history of carcinoma in situ and malignant disease, except for adequately treated non-invasive cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
Abnormal chest X-ray within 12 weeks of Day 1 (locally read and reported by a radiologist) judged by the investigator as clinically-significant.
History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.

Active infections, or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or have required management of acute or chronic infections as follows:

Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria).
Hospitalisation for treatment of infection within 12 weeks of Day 1.
Use of parenteral (intravenous [IV] or intramuscular [IM]) antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) within 12 weeks of Day 1 or oral antimicrobials within 14 days of Day 1.
Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period.
A vaccination (live or attenuated) within 30 days of Day 1 or Bacillus Calmette-Guérin (BCG) vaccination within 365 days of Day 1, or a live vaccination planned during the course of the study.
The subject has received treatment with the therapies prohibited or changes to those treatments in the prescribed timeframe. Subjects who have previously taken >1 biologic therapy for RA are excluded from this study.
Other medications (including vitamins, herbal and dietary supplements) will be considered on a case-by-case basis, and will be allowed if in the opinion of the investigator the medication will not interfere with the study procedures or compromise subject safety.
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 millilitre [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Smokers who would not be able to refrain from smoking whilst in the clinic.
Subjects who cannot refrain from consuming any of the following fruits or juices (alone or in combination): seville oranges, grapefruit, pummelos, or any citrus fruits from 7 days prior to the first dose of study medication until their discharge from the unit after their last dose of study medication.
History of sensitivity to any components of the study medication, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
Serologic evidence of current/previous Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg) and anti-Hepatitis B core (anti-HBc) antibody as follows within 6 weeks of Day 1: Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded
Hepatitis C: Positive test for Hepatitis C virus (HCV) antibody confirmed on a subsequent blood sample by Ribonucleic acid (RNA)-polymerase chain reaction (PCR) assay within 6 weeks of Day 1. Subjects who are positive for Hepatitis C antibody and negative for Hepatitis C RNA-PCR assay performed on a subsequent sample will be eligible to participate. Subjects who are positive for Hepatitis C antibody and have a positive result for Hepatitis C RNA-PCR assay performed on the subsequent sample,will not be eligible to participate.
A positive test for HIV 1 or 2 at screening.

Evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by all of the following:

No history of active or latent TB infection irrespective of treatment status
A negative diagnostic TB test within 28 days of baseline (Day 1) defined as: A negative QuantiFERON Gold test or T-spot test (two successive indeterminate QuantiFERON tests will be considered as a positive result) OR If QuantiFERON gold or T-spot test not approved or registered in country of participation, then a negative tuberculin skin test (TST) reaction as per local guidelines is required (it is strongly recommended that subjects with a history of BCG vaccination be tested with QuantiFERON gold test).
Chest X-ray within 12 weeks of Day 1 with no evidence of current or previous pulmonary tuberculosis, locally read by a radiologist.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Participation in a trial with any investigational drug within 3 months or 5 half-lives (whichever is longer) before the start of the study and within 4 months if the study drug was new chemical entity. Exposure to more than 3 new chemical entities in a clinical study setting within 12 months prior to the first dosing day.
Donation of blood in excess of 500 mL within a 56 day period prior to dosing.