Belimumab is a full humanized IgGl-X monoclonal antibody with a organism molecular collection of 147000. It is produced by recombinant DNA subject. Belimumab selectively binds to alto kinship kinship to explicable BAFF in humor, preventing it from binding to Organ costive, thereby inhibiting B room proliferation and discrimination into antibody-producing ecf cells, causing apoptosis of autoimmune B cells, thereby reaction autoantibodies in the humor and achieving therapeutic purposes.
State I clinical run
State I clinical trials were performed on 70 patients with temperate to moderationist SLE to determine their device, biological manifestation, and pharmacokinetics. These patients were arbitrarily trifid into 5 groups, receiving belimumab and placebo at 1, 4, 10, and 20 mg / kg. The results showed that the most unrefined harmful reactions were supply upset, cephalalgia, diarrhea, symptom, and symptom. There were no portentous differences in unfavourable reactions between the empirical unit and the command foregather.
The drawing also showed that belimumab showed simple pharmacokinetics in a zen grasp of 1-20 mg / kg. The average dependable denote product organization was 69 ~ 112ml / kg, the spacing period half-life was 1 ~ 2.2d, the contact half-life was 8.5 ~ 14.1d, and the clearance measure was 7ml / kg per day after one management.
There were no operative differences in clearance, half-life, and intensity distribution between solitary and duple doses. State I clinical trials official that the reduction of CD20 + B lymphocytes and anti-ds-DNA antibodies provided the fundament for further clinical trials. The results of this reflection inform that belimumab is innocuous and substantially tolerated in patients with temperate to chair SLE.
Phase II clinical tryout
Form II clinical trials of belimumab were performed in existing patients with SLE disease activeness finger (SELENA-SLEDAI) = 4. Patients can act in standardized trials (including deltasone, antimalarials, and immunosuppressants) while involved in the trial.
Patients were randomly biramous into 4 groups (1, 4, 10 mg / kg) for a add of 336 patients) and placebo (113 patients). Belimumab was administered intravenously on days 0, 14, 28, and every 28 life thereafter. The layer of handling is up to 52 weeks.
At 24 to 52 weeks of direction, the no. intensification dimension was 154 life in the treatment grouping and 108 days in the placebo foregather (P = 0.031). At hebdomad 4, the PGA in the discourse gather denatured; at week 52, the total PGA in the communicating gather belittled by 31% and in the placebo unit by 14% (P = 0.0019). In increase to the melioration in symptoms, 52 At hebdomad measure, the amount of CD19, CD20, activated B cells and plasm cells were also significantly reduced in the handling assemble.