Phase 2
Completed N=15
Evaluation of Pharmacokinetics and Safety of GSK3196165 in Combination With Methotrexate in Japanese Subjects With Rheumatoid Arthritis
Arthritis, Rheumatoid
Source: ClinicalTrials.gov NCT03028467 ↗
Enrolled (actual)
15
Serious AEs
6.7%
Results posted
Jun 2019
Primary outcomePrimary: Maximum Observed Concentration (Cmax) of GSK3196165 — 699.92; 1444.88; 3924.10 Nanogram per milliliter (ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Concentration (Cmax) of GSK3196165 |
699.92; 1444.88; 3924.10 | — |
| PRIMARY 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 |
189948.606; 386497.495; 1186604.746; 732243.847; 1097422.958; 196562.287 | — |
| PRIMARY Time to Reach Cmax (Tmax) of GSK3196165 |
48.99167; 70.61667; 69.80000 | — |
| PRIMARY Terminal Half-life (t1/2) of GSK3196165 |
282.85265; 245.12966 | — |
| PRIMARY Number of Participants With Any Adverse Event (AE), Serious AE (SAE) and Adverse Events of Special Interest (AESI) |
3; 2; 3; 2; 1; 0 | — |
| SECONDARY Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-0.3; -7.7; -15.0; -1.0; -1.8; -6.7 | — |
| SECONDARY Change From Baseline in Heart Rate (HR) |
0.3; -8.0; 11.5; -0.8; 3.0; -5.3 | — |
| SECONDARY Change From Baseline in Body Temperature |
0.00; -0.20; 0.18; 0.05; 0.07; 0.03 | — |
| SECONDARY Change From Baseline in Respiratory Rate |
-2.0; 0.7; -1.0; 0.8; -0.5; 0.0 | — |
| SECONDARY Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings |
1; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Emergent Hematology Results Relative to Normal Range |
1; 0; 1; 0; 3; 3 | — |
| SECONDARY Number of Participants With Emergent Clinical Chemistry Results Relative to Normal Range |
0; 0; 2; 0; 4; 3 | — |
| SECONDARY Number of Participants With Urinalysis Dipstick Findings |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Anti-GSK3196165 Antibody Test Results |
0; 0; 0; 0; 4; 3 | — |
| SECONDARY Change From Baseline in Disease Activity Score for 28 Different Joints C-reactive Protein (DAS28 [CRP]) at All Indicated Timepoints |
-0.2179; -1.3289; -0.7356; -0.7511; 0.1643; -0.9744 | — |
Eligibility Criteria
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 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 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.
Data sourced from ClinicalTrials.gov (NCT03028467). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.