Background/Purpose: Belimumab is a recombinant, human Ig-G1λ monoclonal antibody that binds and antagonizes the biological activity of soluble B-lymphocyte stimulator protein, a member of the tumor necrosis factor ligand superfamily that promotes the survival of B lymphocytes. This study (NCT#01583530) evaluated the absolute bioavailability, PK, tolerability, and safety of belimumab (200 mg/mL) administered SC to healthy subjects as a single dose and as multiple doses up to 240 mg.

Methods: In all, 118 healthy subjects (aged 18−55 y; body weight 51−115 kg) were enrolled. Seventy-eight subjects received a single dose of belimumab 240 mg IV, or 2×120, 1×240, or 1×200 mg SC. Forty subjects received 4 weekly injections of belimumab 2×120 or 1×200 mg SC. Randomization was stratified by weight (< vs ≥ 75 kg) and, for SC administration, by injection site (abdomen vs thigh), with a target enrollment of ~50% women/treatment group. Serial blood samples were collected and the serum belimumab concentrations measured by a validated electrochemiluminescence-based assay. Belimumab PK parameters were derived by noncompartmental or compartmental analysis. 

Results: The bioavailability and PK parameters of belimumab following single IV and SC administration are summarized in the table. Following 4 weekly SC belimumab doses, bioavailability values (90% CI) were 75% (63%−89%) and 78% (67%-91%) for the 2×120- and 1×200-mg SC groups, respectively. Four subjects had persistent positive immune responses; neutralizing antibodies in these subjects were not detected and there was no apparent impact on PK. Single and multiple dosing of belimumab was generally safe and well tolerated, with no severe/serious injection-site reactions, eg, rash, edema, erythema, and pruritus.

Conclusion: Following single belimumab SC doses, bioavailability was 74%−82%, indicating that belimumab SC was well absorbed, and bioavailability was similar among the 3 SC groups. Bioavailability after 4 weekly SC doses was similar to that following single SC administration. Belimumab was generally safe and well tolerated after single and multiple SC dosing.

 

PK and Bioavailability of Belimumab
Parameter	Belimumab
	240 mg IV	2×120 mg SC	1×240 mg SC	1×200 mg SC
No. of subjects	19	19	18	18
tmax, da	0.09 (0.05-0.30)	3.9 (0.9-9.8)	4.9 (2.9-13.9)	5.9 (1.9-13.9)
Cmax, µg/mLb	86.2 (20.2)	32.7 (29.0)	31.6 (27.9)	24.3 (40.3)
AUC0-∞, µg∙d/mLb	1030 (32.1)	788 (36.1)	812 (36.2)	612 (37.9)
t1/2,term, dc	18.2 ± 6.3	15.9 ± 5.3	18.2 ± 6.0	16.0 ± 5.1
F, %d	–	76 (64−90)	82 (70−95)	74 (60−91)
aMedian (range); bgeometric mean (coefficient of variance); cmean ± SD; dabsolute bioavailability (F) and 90% CI. AUC0-∞, area under plasma concentration-time curve from time 0 to ∞; Cmax, maximum plasma drug concentration; tmax, time to reach maximum plasma concentration; t1/2,term, terminal half-life.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bioavailability-pharmacokinetics-and-safety-of-belimumab-administered-subcutaneously-in-healthy-subjects/