PMID- 34554352
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220809
IS  - 2198-6576 (Print)
IS  - 2198-6584 (Electronic)
IS  - 2198-6576 (Linking)
VI  - 8
IP  - 4
DP  - 2021 Dec
TI  - Pharmacokinetics and Safety of Intravenous and Subcutaneous Auto-injector 
      Single-dose Belimumab in Healthy Chinese Volunteers: A phase 1, Randomized, 
      Open-label Study.
PG  - 1711-1724
LID - 10.1007/s40744-021-00366-0 [doi]
AB  - INTRODUCTION: Belimumab is a recombinant human immunoglobulin G1lambda monoclonal 
      antibody indicated as an intravenous (IV) 10 mg/kg and subcutaneous (SC) 200-mg 
      dose for the treatment of systemic lupus erythematosus (SLE). Belimumab 10 mg/kg 
      IV has been approved for the treatment of patients with SLE in China. This phase 
      1 study investigated the pharmacokinetics (PK), safety, and tolerability of 
      belimumab 200 mg SC and the approved IV formulation in a healthy Chinese 
      population. METHODS: This was a 13-week open-label, randomized, parallel-group 
      study in healthy Chinese volunteers. Eligible volunteers were randomized (1:2) to 
      receive a single dose of IV or SC (via auto-injector) belimumab 200 mg. PK and 
      safety endpoints were evaluated using descriptive statistics. RESULTS: Thirty-six 
      healthy Chinese volunteers were enrolled and all completed the study. 
      Concentration-time profiles were as expected for both formulations. Overall, 130 
      adverse events (AEs) were reported, with 28 AEs reported in 11 (91.7%) volunteers 
      in the IV group and 102 AEs in 24 (100%) volunteers in the SC group. Of the 130 
      AEs, 104 (80.0%) were considered to be treatment-related (27 [20.8% of total AEs] 
      treatment-related AEs in the IV group; 77 [59.2% of total AEs] in the SC group). 
      Although the occurrence of AEs was higher in the SC group, most volunteers 
      (91.7%) experienced AEs of mild intensity. The most frequently reported AEs 
      included injection site pain (n = 19 [79.2%]) and oropharyngeal pain (n = 5 
      [20.8%]) in the SC group, and positive bacterial test, upper respiratory tract 
      infection, blood uric acid increase, white blood cell count increase, asthenia, 
      and diarrhea (n = 2 [16.7%], each) in the IV group. CONCLUSIONS: PK profiles of 
      200 mg SC and IV belimumab administrations were similar to previous studies, and 
      safety profiles were acceptable, supporting the use of the SC dose in Chinese 
      patients with SLE. TRIAL REGISTRATION: NCT04136145.
CI  - (c) 2021. The Author(s).
FAU - Meng, Xianmin
AU  - Meng X
AD  - Department of Pharmacy, Shanghai Public Health Clinical Center, Fudan University, 
      Shanghai, China.
FAU - Wang, Qianqian
AU  - Wang Q
AD  - Department of Internal Medicine, Shanghai Public Health Clinical Center, Fudan 
      University, Shanghai, China.
FAU - Wu, Shunquan
AU  - Wu S
AD  - R&D, GlaxoSmithKline, Shanghai, China.
FAU - Pu, Di
AU  - Pu D
AD  - R&D, GlaxoSmithKline, Shanghai, China.
FAU - Zhang, Amber
AU  - Zhang A
AD  - R&D, GlaxoSmithKline, Shanghai, China.
FAU - Fang, Sun
AU  - Fang S
AD  - R&D, GlaxoSmithKline, Shanghai, China.
FAU - Zhou, Xuan
AU  - Zhou X
AD  - Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Shanghai, China.
FAU - Lu, Hongzhou
AU  - Lu H
AUID- ORCID: 0000-0002-8308-5534
AD  - Department of Infectious Diseases and Immunology, Shanghai Public Health Clinical 
      Center, Fudan University, 2901 Caolang Rd, Jinshan District, Shanghai, China. 
      luhongzhou@fudan.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT04136145
PT  - Journal Article
DEP - 20210923
PL  - England
TA  - Rheumatol Ther
JT  - Rheumatology and therapy
JID - 101674543
PMC - PMC8572285
OAB - Systemic lupus erythematosus (SLE) is a long-term autoimmune disease that affects 
      patients' quality of life. Belimumab is an antibody used in several countries in 
      combination with standard therapy to treat patients with SLE. Belimumab can be 
      given monthly either via a vein (intravenous, IV) or weekly under the skin 
      (subcutaneous, SC). In China, only the IV belimumab has been approved for the 
      treatment of patients with SLE. Therefore, we carried out a study in healthy 
      Chinese volunteers to compare the concentration of a single dose of IV or SC 
      belimumab in the body over time, and to investigate the safety of SC belimumab to 
      assist its approval in China. In our study, the concentration and safety of both 
      administration methods were similar; however, more volunteers from the SC 
      treatment group had urinalysis-related side effects compared with the IV 
      treatment group. All of these side effects were of mild intensity and did not 
      require treatment. These results suggest that SC belimumab could be used for the 
      treatment of Chinese patients with SLE.
OABL- eng
OTO - NOTNLM
OT  - Belimumab
OT  - Intravenous
OT  - Monoclonal antibody
OT  - Pharmacokinetics
OT  - Safety
OT  - Subcutaneous
OT  - Systemic lupus erythematosus
EDAT- 2021/09/24 06:00
MHDA- 2021/09/24 06:01
PMCR- 2021/09/23
CRDT- 2021/09/23 12:28
PHST- 2021/05/25 00:00 [received]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2021/09/24 06:01 [medline]
PHST- 2021/09/23 12:28 [entrez]
PHST- 2021/09/23 00:00 [pmc-release]
AID - 10.1007/s40744-021-00366-0 [pii]
AID - 366 [pii]
AID - 10.1007/s40744-021-00366-0 [doi]
PST - ppublish
SO  - Rheumatol Ther. 2021 Dec;8(4):1711-1724. doi: 10.1007/s40744-021-00366-0. Epub 
      2021 Sep 23.