Session Information
Date: Sunday, October 21, 2018
Title: 3S110 ACR Abstract: SLE–Clinical I: Clinical Trials (970–975)
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: The T cell costimulatory molecule, CD28, is critical for the activation of pathogenic T cells in autoimmune diseases.1,2 An anti-CD28 domain antagonist antibody, lulizumab pegol (lulizumab), was evaluated in a Phase 2 study in subjects with active systemic lupus erythematosus (SLE).
Methods: In a 24-week randomized, multicenter, double-blind study of subjects meeting the American College of Rheumatology criteria for SLE3,4, lulizumab was administered SC at doses of 1.25 mg every other week (EOW), 5 mg EOW, 12.5 mg EOW, or 12.5 mg weekly, or placebo (PBO) SC, on a background of standard of care (SOC) medications. Subjects were required to have elevated serum antinuclear antibodies, as well as BILAG “A” (severe) or “B” (moderate) arthritis and/or cutaneous manifestations, and SLEDAI ≥ 6 (at least 4 from clinical features). The maximum dose of corticosteroids could not exceed 30 mg/day of prednisone or equivalent at screening and no more than 10 mg/day at Day 1. The primary endpoint was the proportion of responders using the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) at Day 169 (Week 24).
Results: 349 subjects with SLE were randomized in five treatment arms (N=68-71/arm). There were no differences in the BICLA response rate at Day 169 (PBO = 59.2%, 1.25 mg EOW = 58.6%, 5 mg EOW = 57.4%, 12.5 mg EOW= 63.2% and 12.5 mg weekly=59.4%). Additional efficacy outcome measures (e.g. SRI-4, SRI-6, SRI-8, SLEDAI change from baseline, CLASI change from baseline, CLASI20 and CLASI50) also did not reveal significant differences between groups. Dose-dependent CD28 receptor occupancy correlated with drug exposure. Lulizumab treatment resulted in effects on T and B cell subsets and on markers consistent with the proposed CD28 mechanism of action. Lulizumab appeared to be well-tolerated overall (Table 1).
|
Table 1. Summary of safety over 24 weeks |
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|
PBO (N =71) |
1.25 mg EOW (N=70) |
5 mg EOW (N=68) |
12.5 mg EOW (N=68) |
12.5mg W (N=69) |
|
|
Deaths, n (%) |
0 |
2 (2.9) |
0 |
0 |
0 |
|
SAEs, n (%) |
6 (8.5) |
8 (11.4) |
9 (13.2) |
4 (5.9) |
5 (7.2) |
|
Related SAEs, n (%) |
1 (1.4) |
0 |
5 (7.4) |
3 (4.4) |
3 (4.3) |
|
Discontinued due to SAEs, n (%) |
1 (1.4) |
5 (7.1) |
4 (5.9) |
2 (2.9) |
3 (4.3) |
|
Total subjects with AEs, n (%) |
61 (85.9) |
59 (84.3) |
60 (88.2) |
56 (82.4) |
59 (85.5) |
|
Discontinued due to AEs, n (%) |
3 (4.2) |
9 (12.9) |
9 (13.2) |
5 (7.4) |
8 (11.6) |
|
• 2 deaths in 1.25 mg EOW group were due to cerebral haemorrhage and SLE |
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Conclusion: There was no significant difference between lulizumab and placebo for the primary (BICLA response rate) or secondary endpoints at Week 24, although PD activity was observed. Lulizumab had a favorable safety profile.
References:
- Kow NY, Mak A. Clin Dev Immunol. 2013: 245928.
- Suchard SJ, Davis PM, Kansal S, et al. J Immunol. 2013; 191(9):4599–4610.
- Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. Arthritis Rheum 1982; 25:1271-1277.
- Hochberg MC. Arthritis Rheum 1997; 40:1725
To cite this abstract in AMA style:
Merrill JT, Shevell DE, Duchesne D, Nowak M, Kundu S, Girgis IG, Hu YS, Nadler SG, Banerjee S, Throup J. An Anti-CD28 Domain Antibody, Lulizumab, in Systemic Lupus Erythematosus: Results of a Phase II Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/an-anti-cd28-domain-antibody-lulizumab-in-systemic-lupus-erythematosus-results-of-a-phase-ii-study/. Accessed .ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-anti-cd28-domain-antibody-lulizumab-in-systemic-lupus-erythematosus-results-of-a-phase-ii-study/