Phase 1
Completed N=20
Belimumab Phase I Study in Chinese Subjects With Systemic Lupus Erythematosus
Source: ClinicalTrials.gov NCT02880852 ↗Enrolled (actual)
20
Serious AEs
5.0%
Results posted
Nov 2018
Primary outcomePrimary: Maximum Observed Concentration (Cmax) of Belimumab — 221.3532 Micrograms per milliliter
Summary
In China, Belimumab (GSK1550188) will be developed for a dosing regimen of once-monthly intravenous (IV) infusion for the treatment of SLE. This open-label, single dose study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of belimumab in Chinese SLE subjects. A total of approximately 20 subjects will be enrolled to receive IV infusion of 10 milligrams per kilogram (mg/kg) GSK1550188 on Day 0 for the treatment of SLE. Subjects will be followed for 84 days after the administration of drug.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Concentration (Cmax) of Belimumab |
221.3532 | — |
| PRIMARY Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t]) and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0 to Inf]) of Belimumab |
2395.3030; 2461.8013 | — |
| PRIMARY Terminal Phase Half-life (t1/2) of Belimumab |
14.6283 | — |
| PRIMARY Terminal Phase Rate Constant (Lambda z) of Belimumab |
0.0474 | — |
| PRIMARY Systemic Clearance (CL) of Belimumab |
4.0621 | — |
| PRIMARY Volume of Distribution (Vz) of Belimumab |
85.7265 | — |
| PRIMARY Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) |
12; 1 | — |
| SECONDARY Change From Baseline to Day 84 in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-0.5; -1.5; -2.1; -0.1; 2.2; 1.1 | — |
| SECONDARY Change From Baseline to Day 84 in Vital Sign- Pulse Rate |
-1.2; -1.6; 2.6; 2.3; 5.7; 4.7 | — |
| SECONDARY Change From Baseline to Day 84 in Vital Sign- Temperature |
0.21; 0.17; 0.20; 0.40; 0.24; 0.40 | — |
| SECONDARY Number of Participants With Abnormal-clinically Significant 12-lead Electrocardiogram (ECG) Findings |
— | — |
| SECONDARY Change From Baseline to Day 84 in Clinical Chemistry Parameters- Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase |
-1.6; -1.3; -3.2; -5.0; -5.5; -3.9 | — |
| SECONDARY Change From Baseline to Day 84 in Clinical Chemistry Parameters- Albumin and Protein |
-1.4; -1.1; -0.6; -0.5; -0.6; -3.8 | — |
| SECONDARY Change From Baseline to Day 84 in Clinical Chemistry Parameters- Bilirubin, Creatinine, Direct Bilirubin, Indirect Bilirubin and Urate |
-2.8; -2.4; -3.4; -3.2; -2.1; -0.18 | — |
| SECONDARY Change From Baseline to Day 84 in Clinical Chemistry Parameters- Calcium, Calcium Corrected, Carbon Dioxide, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea and Glucose |
-0.040; -0.020; 0.004; -0.020; -0.027; -0.010 | — |
| SECONDARY Change From Baseline to Day 84 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets |
-0.006; -0.011; -0.013; -0.008; -0.005; -0.019 | — |
| SECONDARY Change From Baseline to Day 84 in Hematology Parameter- Erythrocytes |
-0.12; -0.19; -0.13; -0.16; -0.18 | — |
| SECONDARY Change From Baseline to Day 84 in Hematology Parameter- Hematocrit |
-0.0112; -0.0176; 0.0006; -0.0060; -0.0126 | — |
| SECONDARY Change From Baseline to Day 84 in Hematology Parameter- Hemoglobin |
-3.7; -5.0; -4.0; -5.0; -5.7 | — |
| SECONDARY Number of Participants With Positive Urinalysis Dipstick Results |
1; 1; 1; 1; 1; 5 | — |
| SECONDARY Percent Change From Baseline to Day 84 in B Cell Subsets (Cluster of Differentiation [CD]19 and CD 20+) for Pharmacodynamic Assessment |
26.6444; -4.1141; -12.6852; -20.4908; -27.0912; 35.3407 | — |
| SECONDARY Percent Change From Baseline to Day 84 in B Cell Subsets (CD20+/27+ Memory and CD20+/27-naïve) for the Pharmacodynamic Assessment |
186.4701; 118.1433; 91.2965; 135.8139; 70.6332; 4.0530 | — |
| SECONDARY Percent Change From Baseline to Day 84 in Immunoglobulins B Cell Subset (Normalized [Norm] CD19+/27BRIGHT[Br]/38Br SLE Subset, Norm CD20+/138+Plasmacytoid, Norm CD20+/69+Activated and Norm CD20-/CD138+Plasma Cell) for Pharmacodynamic Assessment |
5.3271; -4.4623; 17.2492; 48.1481; 24.9838; 200.6464 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects who give consent to this study participation and sign informed consent form.
- Subjects at least 18 years of age inclusive at screening visit.
- SLE Classification: Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 ACR criteria present, serially or simultaneously during any interval or observation.
- SLE Treatment: Be on either no SLE medication or a stable SLE treatment regimen of any medication (alone or in combination) for a period of at least 2 months prior to Day 0; corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day); immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), mizoribine, calcineurin inhibitors (example [e.g.], tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide; anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine) and non-steroidal anti-inflammatory drugs (NSAIDs).
- The subjects with positive test for anti-nuclear antibody (ANA) or anti-double stranded deoxyribonucleic acid (DNA) serum antibody.
- Males and females: A female subject is eligible to enter the study if she is: not pregnant or nursing; of non-childbearing potential (i.e., women who had a hysterectomy, are postmenopausal which is defined as 1 year without menses, have both ovaries surgically removed or have current documented tubal ligation); of childbearing potential (i.e., women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea [even severe], women who are perimenopausal or have just begun to menstruate. These women must have a negative serum pregnancy test at screening, and agree to one of the following: complete abstinence from penile-vaginal intercourse, when this is the female's preferred and usual lifestyle, from 2 weeks prior to administration of the 1st dose of investigational product (IP) until study complete; or consistent and correct use of one of the following acceptable methods of birth control for 1 month prior to the start of the IP and for 16 weeks after the last dose of IP: any intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1 percent (%) per year; oral contraceptives; double barrier method with vaginal spermicidal agent: condom and an occlusive cap (cervical cap/vault or diaphragm) with a vaginal spermicidal agent (foam/gel/film/cream/suppository); implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; injectable progesterone; percutaneous contraceptive patch; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subject.
- Based on single or averaged corrected QT (QTc) interval values of triplicate ECGs obtained over a brief recording period: [QTc corrected by Bazett's (QTcB) or QTc corrected by Fridericia's (QTcF) formula] 60 mg/day) within 6 months prior to Day 0.
- The subject has received a non-biologic investigational agent within 2 months prior to Day 0.
- The subject is currently participating in another clinical study or post-marketing study in which the subject is or will be exposed to an investigational agent.
- The subject has severe lupus kidney disease (defined by proteinuria >6 grams [g]/24 hours) within 6 months prior to the Screening visit.
- History of renal transplant.
- Active central nervous system (CNS) lupus [including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), motor neuropathy, vasculitis] requiring medical intervention within 6 months prior to Screening visit.
- Infections: Have required management of acute or chronic infections, as follows: currently on any suppressive therapy for
Data sourced from ClinicalTrials.gov (NCT02880852). 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.