Not provided
Not provided
Not provided
Not provided
Not provided
This study was stopped before any subjects were treated, consequently there are no results for the study.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Chemokine (C-C motif) ligand 20 (CCL20) is a protein involved in attracting immune cells including subsets of T cells (for example Th17 cells), B cells, natural killer cells and dendritic cells to inflamed tissues in conditions such as psoriasis (Ps) and psoriatic arthritis (PsA). CCL20 acts by binding and activating the chemokine receptor 6 (CCR6) present on the surface of the inflammatory cells. Levels of CCL20 are increased in inflamed tissues in psoriasis (Ps) and inflammatory arthritis. GSK3050002 is a humanized Immunoglobulin G (Ig)G monoclonal antibody, which binds to and neutralizes the action of human CCL20. The hypothesis is that GSK3050002 will reduce the movement of inflammatory cells into tissues affected by Ps or PsA, thereby leading to an improvement in disease activity. The primary objective of this multi-centre, randomized, double-blind (sponsor open), placebo-controlled trial is to evaluate the safety and tolerability of repeat doses of GSK3050002, and to understand the mechanism of action (by taking skin and synovial biopsy samples) and potential for clinical efficacy of GSK3050002 in subjects with PsA. A minimum of 18 subjects and up to a maximum of 30 subjects will be randomised into the study to either GSK3050002 or placebo in a 2:1 ratio to ensure that approximately 18 evaluable subjects complete the study. The total duration of participation in the study will be approximately 21 weeks from screening to last study visit.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK3050002 100 mg/mL | Experimental | Subjects will be administered GSK3050002 intravenously (IV) over the period of approximately 2 hours on Day 1, Day 15 and Day 29 (total of 3 doses) in a clinical facility with regular monitoring of vital signs. Monitoring of vital signs will continue for a minimum of 2 hours after completion of Infusion. On Day 1, loading dose of GSK3050002 10 milligrams per kilogram (mg/kg) will be administered intravenously, followed by maintenance doses of 5mg/kg IV administered at Day 15 and Day 29. Each subject will receive a cumulative dose of 20 mg/kg. |
|
| Placebo | Placebo Comparator | Subjects will be administered normal saline (0.9% sodium chloride) intravenously over the period of approximately 2 hours on Day 1, Day 15 and Day 29 (total of 3 doses) in a clinical facility with regular monitoring of vital signs. Monitoring of vital signs will continue for a minimum of 2 hours after completion of Infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK3050002 | Drug | The 3 mL glass vial contains white to off-white lyophilized powder which requires reconstitution with sterile water for injection.Prepared as 100 milligrams per milliliter (mg/mL) solution; lower concentrations prepared by dilution with 0.9% weight by volume (w/v) sodium chloride Injection for infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with Adverse Events (AE) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Up to Day 116 |
| Number of subjects with Serious Adverse Events | An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that jeopardizes the subjects or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, and is associated with drug-induced liver injury. | Up to Day 116 |
| Composite of clinical laboratory assessments as a measure of safety and tolerability. | Clinical laboratory assessments will include hematology, clinical chemistry and urinalysis. | Up to Day 116 |
| Composite of vital signs as a measure of safety and tolerability. | Vital signs to be measured in semi-supine position after at least 5 minutes rest and will include temperature, systolic and diastolic blood pressure, and pulse rate. | Up to Day 116 |
| Electrocardiogram (ECG) assessment as a measure of safety and tolerability. | A single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. | Up to Day 116 |
| Measure | Description | Time Frame |
|---|---|---|
| GSK3050002- CCL20 complex levels in serum | Blood samples will be collected on baseline (Day-10 to -1), at pre-dose and at 120 minutes post start of infusion, immediately after infusion has ceased on D 15 and D 29, D 43, D 85, D 113 +/- 3 days | Baseline and Up to Day 116 |
| Change from baseline in the number of CD3+ T cells synovial tissue and skin biopsy in samples |
Not provided
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:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Oxford | OX3 7LD | United Kingdom |
Not provided
| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| D015535 | Arthritis, Psoriatic |
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
Not provided
Not provided
| ID | Term |
|---|---|
| C000626978 | GSK3050002 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Normal saline (0.9% sodium chloride) will be used as placebo. |
|
Synovial and skin lesion biopsy tissue will be collected and evaluated for general appearance and inflammatory infiltrate including CD3+ T-cells |
| Baseline and Day 43 |
| Change from baseline in Disease Activity Score 28 (DAS28) | DAS28 is a composite arthritis disease activity index comprising swollen and tender joint count (28 joints), patient global assessment of disease activity, and C-reactive protein. | Baseline and Up to Day 116 |
| Changes in American College of Rheumatology (ACR) responders | ACR is a composite score of the patient assessment of joint pain, the patient global assessment of disease activity, the physician global assessment of disease activity, the 66/68 swollen/tender joint count, the Disability Index of the Health Assessment Questionnaire (HAQ-DI) questionnaire, and C-reactive protein. The ACR is reported as % improvement (20%, 50% or 70%), between two discrete timepoints, as calculated by improvement in the 66/68 swollen/tender joint count, and improvement in at least three of the remaining five composite parameters. | Baseline and Up to Day 116 |
| Changes from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS) | PASDAS is a composite disease activity index for psoriatic arthropathies comprising the 66/68 swollen/tender joint count, patient global assessment of disease activity, physician global assesment of disease activity, Leeds enthesitis index, dactylitis score, SF-36 questionnaire and C-reactive protein | Baseline and Up to Day 116 |
| Changes in Psoriasis Lesion Severity Score (PLSS) | The PLSS is the sum of the erythema, scaling and plaque thickness scores. | Baseline and Up to Day 116 |
| Changes in Psoriasis Area Severity Index (PASI) | The PASI scoring system is a widely-used standard clinical tool for assessing the severity of psoriasis that takes into account the overall severity of erythema (redness), thickness (induration), and scale, as well as the extent of body surface area (BSA) affected with psoriasis. Higher scores indicate more severe disease. PASI is a static measurement made without reference to previous scores | Baseline and Up to Day 116 |
| Incidences of serum anti- GSK3050002 antibody levels | Serum samples will be collected from all subjects at pre-dose and various time points post-dosing. An assay for detecting Anti-drug Antibodies (ADAs) against GSK3050002 will be done using validated electrochemiluminescent (ECL) bridging assay and the Meso-Scale Discovery (MSD) technology. | Baseline and Up to Day 116 |
| Titres of serum anti- GSK3050002 antibody levels | The serum which contain potential anti-GSK3050002 antibodies will be confirmed by immunocompetition using excess drug. Confirmed samples with ADA will be further analyzed for titers. | Baseline and Up to Day 116 |
| Maximum serum concentrations (Cmax) after repeat dosing of GSK3050002 | Blood samples were collected at pre-dose and at 120 minutes post start of infusion, immediately after infusion has ceased on Day (D)1, D15, and D29. Blood samples were also collected D 8, D 22, D 43, D 57, D 85 and D 113 +/-3 days. | Up to Day 116 |
| Area under curve over the dosing interval AUC (0- tau) after repeat dosing of GSK3050002 | Blood samples were collected at pre-dose and at 120 minutes post start of infusion, immediately after infusion has ceased on Day (D)1, D15, and D29. Blood samples were also collected D 8, D 22, D 43, D 57, D 85 and D 113 +/-3 days. | Up to Day 116 |
| Systemic clearance (CL) after repeat dosing of GSK3050002 | Blood samples were collected at pre-dose and at 120 minutes post start of infusion, immediately after infusion has ceased on Day (D)1, D15, and D29. Blood samples were also collected D 8, D 22, D 43, D 57, D 85 and D 113 +/-3 days. | Up to Day 116 |
| Volume of distribution (V) after repeat dosing of GSK3050002 | Blood samples were collected at pre-dose and at 120 minutes post start of infusion, immediately after infusion has ceased on Day (D)1, D15, and D29. Blood samples were also collected D 8, D 22, D 43, D 57, D 85 and D 113 +/-3 days. | Up to Day 116 |
| D013122 |
| Spinal Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |