Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 9 for:    GSK3196165

Evaluation of Pharmacokinetics and Safety of GSK3196165 in Combination With Methotrexate in Japanese Subjects With Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03028467
Recruitment Status : Completed
First Posted : January 23, 2017
Results First Posted : June 26, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE January 10, 2017
First Posted Date  ICMJE January 23, 2017
Results First Submitted Date  ICMJE December 12, 2018
Results First Posted Date  ICMJE June 26, 2019
Last Update Posted Date June 26, 2019
Actual Study Start Date  ICMJE January 24, 2017
Actual Primary Completion Date December 20, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Maximum Observed Concentration (Cmax) of GSK3196165 [ Time Frame: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155 ]
    Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by non-compartmental analysis using the concentration data after last dosing (Day 71). Only those participants whose parameters could be determined were analyzed. PK Population included all GSK3196165-treated participants from whom PK samples were collected and analyzed.
  • Area Under the Concentration-time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]), AUC From Time Zero Extrapolated to Infinity (AUC [0-inf]), AUC Over the Dosing Interval (AUCtau) of GSK3196165 [ Time Frame: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155 ]
    Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by non-compartmental analysis using the concentration data after last dosing (Day 71). NA indicates data was not available as geometric mean and/or 95 percent confidence interval could not be calculated when number of participant was not sufficient.
  • Time to Reach Cmax (Tmax) of GSK3196165 [ Time Frame: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155 ]
    Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by non-compartmental analysis using the concentration data after last dosing (Day 71).
  • Terminal Half-life (t1/2) of GSK3196165 [ Time Frame: Pre-dose on Days 1, 8, 15, 29, 57 and 71; anytime during visit on Days 3, 74, 85, 106, 127 and 155. ]
    Blood samples were collected at pre-dose on Days 1, 8, 15, 29, 57 and 71; and at any time during visit on Days 3, 74, 85, 106, 127 and 155. PK parameters were calculated by standard non-compartmental analysis from the concentration data after last dosing (Day 71). NA indicates data was not available as 95 percent confidence interval could not be calculated when number of participant was not sufficient.
  • Number of Participants With Any Adverse Event (AE), Serious AE (SAE) and Adverse Events of Special Interest (AESI) [ Time Frame: Up to 22 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. AESI included serious infections including serious respiratory infections and tuberculosis and opportunistic infections, neutropenia (grade 3 or 4), respiratory events, pulmonary alveolar proteinosis, hypersensitivity reactions including anaphylaxis and injection site reactions.
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
  • Maximum concentration (Cmax) of GSK3196165 calculated from sparse sampling concentrations [ Time Frame: Up to 22 weeks ]
  • Time to maximum concentration (Tmax) of GSK3196165 calculated from sparse sampling concentrations [ Time Frame: Up to 22 weeks ]
  • Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time AUC (0-infinity) [ Time Frame: Up to 22 weeks ]
  • Area under the concentration-time curve over the dosing interval (AUCtau) of GSK3196165 calculated from sparse sampling concentrations [ Time Frame: Up to 22 weeks ]
  • Elimination half life (t1/2) of GSK3196165 calculated from sparse sampling concentrations [ Time Frame: Up to 22 weeks ]
  • Number of subjects with any adverse event (AE) [ Time Frame: Up to 26 weeks ]
    An AE is any untoward medical occurrence in a subject, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product.
  • Number of subjects with any serious adverse event (SAE) [ Time Frame: Up to 26 weeks ]
    A SAE is any untoward medical occurrence that is life threatening, requires prolonged hospitalisation, may result in death, disability and congenital anomaly.
  • Number of subjects with any AE of special interest [ Time Frame: Up to 26 weeks ]
Change History Complete list of historical versions of study NCT03028467 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2019)
  • Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline and up to 22 weeks ]
    Vital sign measurements including SBP and DBP were measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.
  • Change From Baseline in Heart Rate (HR) [ Time Frame: Baseline and up to 22 weeks ]
    Vital sign measurements including HR was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.
  • Change From Baseline in Body Temperature [ Time Frame: Baseline and up to 22 weeks ]
    Vital sign measurements including body temperature was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.
  • Change From Baseline in Respiratory Rate [ Time Frame: Baseline and up to 22 weeks ]
    Vital sign measurements including respiratory rate was measured after 5 minutes rest before each reading. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value.
  • Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings [ Time Frame: At Week 12 ]
    12-Lead ECGs were taken using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) intervals. Number of participants with any abnormal findings in ECG recordings were summarized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
  • Number of Participants With Emergent Hematology Results Relative to Normal Range [ Time Frame: Up to 22 weeks ]
    Blood samples were collected to evaluate hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), erythrocytes, reticulocytes, white blood cells (WBC), total neutrophils, eosinophils, basophils, monocytes, lymphocytes, platelet count, activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen, erythrocyte sedimentation rate (ESR). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose lab value category was unchanged (e.g. High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if they had values that changed 'To Low' and 'To High', so the percentages may not add to 100% in such instances.
  • Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range [ Time Frame: Up to 22 weeks ]
    Blood samples were collected to evaluate Albumin, Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Total Bilirubin, Calcium, Cholesterol, Creatine Kinase, C-Reactive protein (CRP), Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, High Density Lipids (HDL), Potassium, Lactate Dehydrogenase, Low Density Lipids (LDL), Sodium, Phosphorus inorganic, Triglycerides, Total Protein and Urea. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose lab value category was unchanged (e.g. High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if they had values that changed 'To Low' and 'To High', so the percentages may not add to 100% in such instances.
  • Number of Participants With Urinalysis Dipstick Findings [ Time Frame: Up to 22 weeks ]
    Urine samples were collected for analysis of presence of glucose and protein in urine by dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine protein and glucose can be read as negative, Trace, 1+, 2+ and 3+, indicating proportional concentrations in the urine sample
  • Number of Participants With Anti-GSK3196165 Antibody Test Results [ Time Frame: Weeks 2, 4, 12 and 22 ]
    Serum samples were collected and tested for presence of antibodies that bind to GSK3196165. The presence of treatment emergent anti-drug antibodies (ADA) were determined using a GSK3196165 bridging style ADA assay with a bio-analytically determined cut point determined during assay validation. Samples taken after dosing with GSK3196165 that have a value at or above the cut-point were considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Baseline was considered as the latest pre-dose assessment. Number of participants with post-Baseline negative or positive anti-GSK3196165 antibody test results were presented.
  • Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints [ Time Frame: Baseline, up to Week 22 ]
    DAS28 (CRP) is a measure of disease activity in rheumatoid arthritis obtained by examination of 28 joints for swelling and tenderness using CRP as a blood biomarker for inflammation. Its components include: Tender/Painful Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), CRP and Patient's Global Assessment of Arthritis. DAS28 (CRP) was calculated by 0.56 (square root of TJC28)+ 0.28 (square root of SJC28)+ 0.36 (natural logarithm [CRP+1])+ (0.014*patients global assessment)+0.96. Scores ranges from 0 to infinity, where higher scores indicates high disease activity. Scores higher than 5.1 indicates high disease activity and scores lower than 2.6 indicates remission. Baseline was considered as the latest pre-dose assessment. The change from Baseline is defined as the difference between the post-dose visit value and Baseline value. Adjusted mean and standard error of adjusted mean are presented using Mixed Model for Repeated Measures.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
  • Change from baseline in vital sign values [ Time Frame: Up to 22 weeks ]
    Vital signs will be measured after 5 minutes rest and will include temperature, systolic and diastolic blood pressure, pulse rate and respiratory rate.
  • Number of subjects with abnormal 12-lead electrocardiogram (ECG) findings [ Time Frame: Up to 22 weeks ]
  • Average of laboratory values [ Time Frame: Up to 22 weeks ]
    Hematology, clinical chemistry, and urinalysis parameters will be measured.
  • Change from baseline in disease activity score for 28 different joints (C-reactive protein) [DAS28(CRP)] at all assessment timepoints [ Time Frame: Up to 22 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Pharmacokinetics and Safety of GSK3196165 in Combination With Methotrexate in Japanese Subjects With Rheumatoid Arthritis
Official Title  ICMJE A Phase 1/2, Double-Blind, Placebo-Controlled Study of the Pharmacokinetics, Safety and Tolerability of GSK3196165 in Combination With Methotrexate Therapy, in Japanese Subjects With Active Moderate-Severe Rheumatoid Arthritis Despite Treatment With Methotrexate
Brief Summary This is a randomized, double-blind, parallel group, 3 dosage level, placebo-controlled, Phase 1/2 study designed to evaluate the pharmacokinetics, safety, tolerability, and efficacy of the monoclonal antibody GSK3196165, in Japanese subjects with active moderate-severe rheumatoid arthritis (RA) despite treatment with methotrexate(MTX). The subjects will receive GSK3196165 in combination with methotrexate therapy for the 12 weeks of treatment period. Approximately 55 subjects will be screened to achieve 40 randomized subjects, so as to have approximately 10 subjects in each treatment group.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: GSK3196165 Dose 1
    GSK3196165 is supplied as liquid and will be administered as SC injection.
  • Drug: GSK3196165 Dose 2
    GSK3196165 is supplied as liquid and will be administered as SC injection.
  • Drug: GSK3196165 Dose 3
    GSK3196165 is supplied as liquid and will be administered as SC injection.
  • Drug: Methotrexate
    Methotrexate capsule/tablet 8-16 mg per week is given orally.
  • Drug: Placebo
    Placebo is supplied as liquid as sterile 0.9% sodium chloride solution and will be administered as SC injection.
  • Drug: Folic acid
    Folic acid tablet 5 mg per week is given orally.
Study Arms  ICMJE
  • Experimental: GSK3196165 Dose 1
    Participants will receive GSK3196165 Dose 1 weekly as a single subcutaneous (SC) injection by an un-blinded administrator. There will be 5 weekly injections (Days 1, 8, 15, 22 and 29), then every other week (EOW) injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants will also receive a stable dose of methotrexate during the Treatment Period.
    Interventions:
    • Drug: GSK3196165 Dose 1
    • Drug: Methotrexate
    • Drug: Folic acid
  • Experimental: GSK3196165 Dose 2
    Participants will receive GSK3196165 Dose 2 weekly as a single SC injection by an un-blinded administrator. There will be 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants will also receive a stable dose of methotrexate during the Treatment Period.
    Interventions:
    • Drug: GSK3196165 Dose 2
    • Drug: Methotrexate
    • Drug: Folic acid
  • Experimental: GSK3196165 Dose 3
    Participants will receive GSK3196165 Dose 3 weekly as a single SC injection by an un-blinded administrator. There will be 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants will also receive a stable dose of methotrexate during the Treatment Period.
    Interventions:
    • Drug: GSK3196165 Dose 3
    • Drug: Methotrexate
    • Drug: Folic acid
  • Placebo Comparator: Placebo
    Participants will receive placebo weekly as a single SC injection by an un-blinded administrator. There will be 5 weekly injections (Days 1, 8, 15, 22 and 29), then EOW injections at Days 43, 57 and 71 (Weeks 6, 8 and 10 respectively). Participants will also receive a stable dose of methotrexate during the Treatment Period.
    Interventions:
    • Drug: Methotrexate
    • Drug: Placebo
    • Drug: Folic acid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 9, 2018)
15
Original Estimated Enrollment  ICMJE
 (submitted: January 19, 2017)
40
Actual Study Completion Date  ICMJE December 20, 2017
Actual Primary Completion Date December 20, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age: >=20 years at the time of signing informed consent - Japanese rheumatoid arthritis (RA) subjects who meets American College of Rheumatology or European League Against Rheumatism (ACR/EULAR) 2010 RA Classification Criteria
  • Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA
  • Disease duration of >=12 weeks (time from onset of subject-reported symptoms of either pain or stiffness or swelling in hands, feet or wrists).
  • Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint count) at screening and at Day 1
  • DAS28(CRP) >=3.2 at screening
  • C-Reactive Protein (CRP) >=0.5 milligrams (mg)/deciliter (dL) at screening
  • Must have previously received methotrexate (MTX) (8-16 mg weekly) orally for at least 12 weeks before screening, with a stable and tolerated dose for >=4 weeks prior to Day 1
  • >=40 kilograms (kg) - Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria
  • Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications
  • Willing to continue or initiate treatment with oral folic acid (5 mg/week) and be treated during the entire study (mandatory co-medication for MTX treatment)
  • Diffusing capacity of lung for carbon monoxide (DLCO) >=60% predicted; forced expiratory volume in 1 second (FEV1) >=70% predicted; forced vital capacity (FVC) >=80% predicted

    • For subjects with DLCO values ≥60% to <70%, a baseline chest high-resolution computed tomography (HRCT) must be performed during the screening period, and it is recommended that the subject be reviewed by a local pulmonologist to exclude significant pre-existing respiratory disease.
  • No 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 T-spot test within 4 weeks of baseline (Day 1)
    • Chest X-ray within 12 weeks of Day 1, locally read by a radiologist, with no evidence of current or previous pulmonary tuberculosis

Exclusion Criteria:

  • Pregnant or lactating women
  • History of other inflammatory rheumatologic or autoimmune disorders, other than Sjögren's syndrome secondary to RA
  • History of any respiratory disease which (in the opinion of the investigator) would compromise subject safety or the ability of the subject to complete the study (e.g. significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary alveolar proteinosis (PAP)
  • Clinically-significant or unstable (in the opinion of the investigator) persistent cough or dyspnea that is unexplained
  • QT interval corrected for heart rate (QTc) >450 milliseconds (msec) or QTc >480 msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF)
  • Liver function tests: alanine aminotransferase (ALT) >=1.5x upper limit of normal (ULN); aspartate transaminase (AST) >=1.5xULN; alkaline phosphatase and bilirubin >=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment)
  • Clinically significant unstable or uncontrolled acute or chronic disease (e.g., cardiovascular including uncompensated congestive cardiac failure New York Heart Association [NYHA] III or IV, myocardial infarction within 12 months, unstable angina pectoris, uncontrolled hypertension, uncontrolled hypercholesterolemia) pulmonary, hematologic, gastrointestinal (including Crohn's Disease or ulcerative colitis), hepatic, renal, neurological, psychiatric, malignancy, endocrinological or infectious diseases, which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk
  • A history of malignant neoplasm within the last 10 years or breast cancer within the last 20 years, except for non-melanoma skin cancers that have been excised and cured or carcinoma in situ of the uterine cervix
  • Kidney disease: Current or history of renal disease, or estimated creatinine clearance <60 milliliter (mL)/minute (min)/1.73 m2 (MDRD formula) or serum creatinine >1.5xULN within 4 weeks of Day 1
  • Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency
  • 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)
    • OR Hospitalization for treatment of infection within 26 weeks of Day 1
    • OR Use of parenteral (Intravenous (IV) or Intramuscular (IM) antimicrobials (antibacterials, antivirals, antifungals, or antiparasitic agents) within 26 weeks of Day 1 or oral antimicrobials within 2 weeks of Day 1
  • A vaccination (live or attenuated) within 30 days of Day 1 or Bacillus Calmette-Guérin (BCG) vaccination within 1 year of Day 1, or a live vaccination planned during the course of the study (including follow-up period).
  • 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 (including follow-up period)
  • Use of prohibited medications Prior to AND throughout the study:

Any conventional DMARDs other than MTX (including sulfasalazine, bucillamine, iguratimod, tacrolimus) should be withdrawn at least 2 weeks prior to Day 1.

Subjects may require longer to discontinue azathioprine or leflunomide prior to Day 1: Azathioprine must be discontinued >=4 weeks prior to randomization; Leflunomide must be discontinued >=12 weeks prior to Day 1 (or >=14 days after 11 days of standard cholestyramine or activated charcoal washout).

  • For these subjects, written informed consent for the study must be obtained prior to beginning the screening period. However, other screening assessments, other than consent, must occur within 4 weeks prior to Day 1.
  • Any biologic agents (such as Tumor necrosis factor (TNF) inhibitors [including adalimumab, etanercept, infliximab, certolizumab pegol, golimumab] or non-TNF inhibitors [including abatacept, rituximab, tocilizumab, belimumab]).
  • Any Janus kinase (JAK) inhibitors (such as tofacitinib).
  • Any anti-rheumatic investigational compounds.
  • Any alkylating agents (such as cyclophosphamide).
  • Plasmapheresis or intravenous immunoglobulin (IVIG) within 26 weeks of Day 1.

Corticosteroids:

  • Any Intramascular (IM), Intravenous (IV) or Intra-arterial (IA) corticosteroids within 8 weeks of Day 1.
  • Oral corticosteroids:

    • Any treatment with >10 mg/day dose oral prednisolone (or equivalent) within 4 weeks of Day 1.
    • New oral corticosteroid or changes in corticosteroid dose within the 4 weeks prior to Day 1. (New topical steroids and immunosuppressive agents (e.g., eye drops, creams) are permitted)
  • Non-steroidal anti-inflammatory drugs (NSAIDs):

    • New or change in dose of NSAID within 2 weeks of Day 1
  • Any non-anti-rheumatic investigational treatment must be discontinued for at least 4 weeks or 5 half-lives, whichever is longer, prior to Day 1
  • Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within a year prior to Day 1
  • History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation
  • Abnormal chest X-ray within 12 weeks of Day 1 (locally read and reported by a radiologist) judged by the investigator as clinically-significant
  • Any Grade 3 or 4 hematology or clinical chemistry laboratory abnormality, within 4 weeks of Day 1
  • Hemoglobin ≤9 g/dL; white blood cell count ≤3.0 x 109/L; platelet count ≤100 x 109/L; absolute neutrophil count ≤1.5 x 109/L; lymphocyte count ≤0.5 x 109/L within 4 weeks of Day 1
  • 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 4 weeks of Day 1

    • Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded
    • Subjects with positive anti-HBs antibody and HBV-DNA (>=2.1 log copies/mL) are excluded.
  • Hepatitis C: Positive test for Hepatitis C virus (HCV) antibody confirmed on a subsequent blood sample by ribonucleic acid - polymerized chain reaction (RNA-PCR) assay within 4 weeks of Day 1.

    • Subjects who are positive for Hepatitis C antibody and negative when the Hepatitis C RNA-PCR assay is performed on a subsequent sample will be eligible to participate. Subjects who are positive for Hepatitis C antibody and have a positive result for the HCV when the Hepatitis C RNA-PCR assay is performed on the subsequent sample will not be eligible to participate
  • Positive serology for human immunodeficiency virus (HIV) 1 or 2 (within 4 weeks of Day 1)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03028467
Other Study ID Numbers  ICMJE 201789
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
Study Director: GSK Clinical Trials GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
PRS Account GlaxoSmithKline
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP