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Phase 1 Completed N=20 Treatment

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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