Background/Purpose

Staphylococcal protein A (SpA) binds with high affinity to the Fc region of human immunoglobulin G and also to the Fab framework region of immunoglobulin encoded from genes of the VH3 family. At intravenous doses up to 1.5 µg/kg weekly SpA was found to have an acceptable safety profile in a Phase I rheumatoid arthritis (RA) trial. The current Phase I study evaluates the safety and effect on RA disease activity of 6 months of SpA treatment.

Methods

This study enrolled 61 RA patients (pts) at 8 US centers. In Part 1 of the study, 41 pts received 5 weekly doses of either placebo, 1.5, 3, 6 or 12 µg/kg of SpA. Partial results from Part 1 have been reported previously [1]. In Part 2, pts received placebo or a fixed SpA dose of either 240 µg or 420 µg given as 5 weekly doses followed by ‘maintenance’ doses at weeks 8, 12, 16 and 20 (6 months’ total treatment). Adverse events (AEs), pharmacokinetics, anti-SpA antibodies and disease activity (ACR20/50/70, DAS28-CRP, and CDAI [Clinical Disease Activity Index]) are being evaluated over the course of this ongoing study.

Results

Twenty pts were randomized in Part 2: 3 pts (240 µg), 12 pts (420 µg) and 5 pts (placebo). All AEs were Grade 1 or 2 in severity with the exception of 1 pt who experienced Grade 3 influenza (unrelated to treatment) and 1 pt with Grade 3 worsening of arthritis (related to treatment). 9 pts (45%) had related AEs, the most common being transient flare of musculoskeletal symptoms usually occurring 1–3 days post-infusion. In Parts 1 and 2 of the study, there were no deaths or serious AEs considered to be related to SpA. Nine of the 12 pts in the 420 µg SpA arm met per-protocol criteria for efficacy evaluation. For comparative purposes, the control group was pooled from the 15 placebo pts enrolled in Parts 1 and 2; 13 placebo pts met per-protocol criteria for efficacy evaluation. Of the 9 pts in Part 2 that received 420 µg SpA, 56% achieved ACR20 at day 113 vs. 31% of pts in the control group (see table). A similar pattern was seen with the ACR50: on day 113, 33% of 9 SpA-treated pts attained an ACR50 vs. 8% of pts in the control group. 

ACR20 Responders: 420 µg SpA  vs. Placebo
	Study Day
	1	8	15	22	29	43	57	85	113
SpA 420 µg (9 pts)	0%	0%	38%	63%	50%	33%	50%	56%	56%
Placebo (13 pts)	0%	11%	31%	23%	31%	25%	39%	39%	31%

CDAI data also indicated some reduction in disease activity, as 44% of 420 µg pts achieved a CDAI of ≤14 on 3 or more consecutive visits vs. 23% of pts in the control group. SpA and control pts had MDHAQ mean physical function scores of 3.57 and 3.59, respectively, at baseline. By day 85, the change from baseline was –1.17 and –0.59 for SpA and control pts, respectively. At day 113, the change from baseline was –1.38 vs. –0.6, respectively.

Conclusion

• A 6-month regimen of 5 weekly infusions of SpA followed by 4 monthly ‘maintenance’ infusions had an acceptable safety profile in pts with RA. The most common AEs seemed to be associated with transient worsening of musculoskeletal symptoms.
• During a 6-month study period, SpA appeared to result in some reduction in disease activity. Some patients experienced improvements.

 1.  Ann Rheum Dis 2014;73(Suppl2)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-phase-1-dose-ranging-repeated-dose-trial-of-parenteral-staphylococcal-protein-a-prtx-100-in-patients-with-active-rheumatoid-arthritis-on-methotrexate-or-leflunamide-therapy/