Clinical Trial Finder

Inclusion Criteria:

• - Age>=18 years and <=75 years of age at the time of consent.

• - Diagnosis of, and currently active psoriatic arthritis with >=3 tender and >=3 swollen joints, one of which must be either a knee or ankle joint suitable for synovial biopsies.

• - C-reactive protein (CRP) >=3mg/l at the time of screening, thought by the investigator to be due to active PsA.

• - A negative test result for Rheumatoid Factor at screening.

• - Active PsA despite an adequate course of treatment with at least one of the following Disease-modifying anti-rheumatic drugs (DMARDS): methotrexate, sulfasalazine or leflunomide for a minimum of 3 months, with a stable dose prior to screening.

The subject may have received prior treatment for their PsA with up to three oral DMARDS.

• - At least 2 active psoriatic skin lesions >=3centimetre (cm) x 3cm diameter at the time of the screening visit which in the opinion of the investigator will still be present in the Pre- Treatment Phase.

Each plaque should have a total PLSS of >=5, including an induration score of >=2 (moderate or above) and a score of >=1 in erythema and scaling. The PLSS is the sum of the erythema, scaling and induration scores. The skin lesions should be located in areas usually shielded from natural light by clothing (e.g. trunk or proximal extremities) and should not include scalp, inguinal or genital lesions.

• - BMI within the range 18 - 35 kilogram per squared meter (kg/m^2) (inclusive).

• - Female subjects are eligible to participate if they are not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: 1.

Pre-menopausal females with one of the following: a. Documented tubal ligation; b. Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; c. Hysterectomy; d. Documented Bilateral Oophorectomy; e. Reproductive potential and agrees to follow one of the options listed below in the GSK (GlaxoSmithKline) Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until 12 weeks after the last dose of study medication and completion of the follow-up visit at Day 113. 2. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause [refer to laboratory reference ranges for confirmatory levels]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

• - Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until 12 weeks after the last dose of study medication:Vasectomy with documentation of azoospermia; Male condom plus female partner use of one of the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Childbearing potential listed below.

GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penilevaginal intercourse on a long term and persistent basis. a. Contraceptive subdermal implant effectiveness criteria including a <1% rate of failure per year, as stated in the product label. b. Intrauterine device or intrauterine system that meets effectiveness criteria including a <1% rate of failure per year, as stated in the product label c. Oral Contraceptive, either combined or progestogen alone d. Injectable progestogen e. Contraceptive vaginal ring f. Percutaneous contraceptive patches g.Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject.

• - Capable of giving signed informed consent which includes compliance with study procedures and requirements as listed in the consent form and in this protocol

  Exclusion Criteria:

  A subject will not be eligible for inclusion in this study if any of the following criteria apply: - Planned surgical joint procedure, including intra-articular, tendon sheath, or bursal corticosteroid injections, during the study.

• - Intra-articular corticosteroid injection, arthrocentesis or synovial biopsy on the joint that has been identified for biopsy or Magnetic resonance imaging (MRI) within 6 weeks of the Pre-Treatment biopsy and MRI.

• - Has undergone surgery, including synovectomy or arthroplasty, on the joint chosen for biopsy or MRI.

• - History of joint disease, other than PsA, at the knee or ankle joint chosen for biopsy and/or MRI (eg gout, pseudogout, osteoarthritis).

• - Diagnosed with a major chronic inflammatory or connective tissue disease other than Ps and PsA (e.g. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, ankylosing spondylitis).

• - An active infection, or a history of infections as follows: a.

A serious infection, defined as requiring hospitalization or intravenous antiinfectives within 8 weeks prior to Day 1. b. Oral anti-microbials within 14 days of Day 1. c. A history of opportunistic infections within 1 year of screening (e.g. pneumocystis jirovecii, cytomegalovirus pnemonitis, aspergillosis). 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 d.Recurrent or chronic infection or other active infection that, in the opinion of the investigator might cause this study to be detrimental to the subject e. History of Tuberculosis (TB), irrespective of treatment status f. A positive diagnostic TB test at screening defined as a positive QuantiFERON®-TBGold (Registered product of QFT-G; Cellestis Ltd., Carnegie, Australia) test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative, or they have a negative Tuberculin Purified Protein Derivative (PPD) skin test. A positive PPD (Mantoux) test is defined as >=5mm of induration (size of raised lump not redness).

• - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• - Known bleeding or coagulation disorder.

• - Alanine aminotransferase (ALT) and bilirubin >1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• - QT interval corrected (QTc) > 450 milliseconds (msec), or QTc > 480 msec in subjects with Bundle Branch Block.

If a single QTc is abnormal, then the averaged QTc values of triplicate ECGs obtained (each separated by at least 5 min) will be utilized to determine eligibility.

• - Active malignancy or carcinoma in situ in the past 5 years.

There is an exception for basal cell carcinoma or cervical carcinoma in situ if they have had curative surgical treatment.

• - Significant unstable acute illness or uncontrolled chronic disease other than PsA, which in the opinion of the investigator, would preclude the subject from study participation.

• - Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to: a.

Intracranial aneurysm clips (except Sugita) or other metallic objects, b. History of intra-orbital metal fragments that have not been removed by a medical professional, c.Pacemakers or other implanted cardiac rhythm management devices and non-MR compatible heart valves, d.Inner ear implants, e.History of claustrophobia which may impact participation.

• - Receiving treatment with anti-coagulant medications, including warfarin, heparin, thrombin inhibitors, and Factor Xa inhibitors, unless the subject is able to discontinue these medications one week prior to biopsies in the Pre-Treatment Phase and at one week prior to the Day 43 biopsies, unless local guidelines indicate a different timeframe, in which case local guidelines may be followed, taking into account the risk:benefit and the indication for use of those medications.

The anticoagulants may be re-started 3 days after the biopsy, or according to local guidelines.

• - Received treatment with the therapies listed below, within the prescribed timeframe.

If in doubt, or the therapy is not listed, please consult with the medical monitor. Treatment with, cyclosporine, tacrolimus, hydroxychloroquine, azathioprine (28 days prior to Screening until Follow-up) apremilast or tofacitanib (At any time prior to Screening until Follow-up). Intravenous, intra-muscular or intra-articular glucocorticoids (28 days prior to screening until follow up). Topical psoriasis therapies (other than on face and genitals where topical therapy may continue during the study) (14 days prior to Screening until Follow-up).Emollients are allowed except on the day of study visits prior to assessments. Biologic therapies for the treatment of psoriasis, psoriatic arthritis or inflammatory arthritis including but not limited to anti-tumor necrosis factors biologics, etanercept, ustekinumab, secukinumab, rituximab, abatacept or tocilizumab (At any time prior to Screening until Follow-up). Alkylating agents (chlorambucil, cyclophosphamide) (At any time prior to Screening until Follow-up) Investigational biological and nonbiological immunomodulatory therapies (At any time prior to Screening until Follow-up). Psoralen long wave ultraviolet radiation treatment (28 days prior to Screening until Follow-up) Acitretin/Retinoids (28 days prior to Screening until Follow-up). Single treatment phototherapy (Ultraviolet B or self therapy with tanning bed or solarium) (14 days prior to Screening until Follow-up). Live vaccination Live vaccinations are not permitted within (28 days of first dose until 12 weeks after the last dose). If indicated, non-live vaccines (e.g. inactivated influenza vaccines) may be administered whilst receiving GSK3050002 based on an assessment of the benefit: risk (e.g. risk of Therapy Time period decreased responsiveness). Investigators are expected to follow local and/or national guidelines with respect to vaccinations, including against influenza and pneumococcus, in subjects with PsA.

• - A history of drug and alcohol misuse that could interfere with participation in the trial according to the protocol, or in the opinion of the investigator impacts on the physical or mental wellbeing of the subject.

• - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

This include a history of severe drug allergies, including Type I hypersensitivity reactions to parenteral administration of human or murine proteins or monoclonal antibodies.

• - Contraindication to gadolinium contrast agent in accordance with local guidelines.

• - Presence of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• - Platelet count is <100 x 10^9/mL or prothrombin time is above the laboratory upper limit of normal at screening.

• - A positive test for human immunodeficiency virus (HIV) antibody.

• - Estimated GFR (Modification of Diet in Renal Disease [MDRD] calculation) of less than 60 milliliters per minute (mL/min) per 1.73 squared meter /m^2 at screening.