Efficacy and safety of RSLV-132 in patients with SLE: A phase IIa trial

Circulating, extracellular ribonucleic acid is a potent activator of type I interferon which plays a central pathogenic role in systemic lupus erythematosus (SLE). RSLV-132, a catalytically active human RNase I fused with human immunoglobulin G1 fragment crystallizable region, is designed to degrade extracellular RNA, and alleviate chronic inflammation linked with SLE.

Here, we summarize an article by Burge et al.¹ published in Lupus Science & Medicine, evaluating the efficacy and safety of RSLV-132 in patients with SLE in a phase IIa trial.

Study design¹

• This was a double-blind, placebo-controlled, phase IIa, proof-of-concept study in patients with SLE with moderate-to-severe cutaneous disease activity.
• Patients were randomized 2:1 to receive 13 doses (6 months of weekly loading dose followed by 5 months of biweekly dose) of 10 mg/kg RSLV-132 or placebo.
• The primary endpoint was a change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score from baseline to Day 169.
• Secondary endpoints included change from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group 2004 Index (BILAG-2004), and the Physician’s Global Assessment (PGA).
• A subgroup of participants with baseline CLASI score ≥21 and SLEDAI score ≥9 were analyzed with respect to British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) and SLE Responder Index (SRI)-4 responses.

Key findings¹

• Out of the 65 patients who met the eligibility criteria, 12 in the placebo group (mean age, 45.2 years; female, 100%) and 25 in the RSLV-132 group (mean age, 45.3 years; female, 93%) completed the study.

Safety

• The incidence of treatment-emergent adverse events (AE), treatment-related AE, treatment discontinuation, and study termination due to treatment-emergent AE were comparable between arms, while the incidence of treatment-emergent serious adverse events was lower in the RSLV-132 group compared with the placebo group (7.1% vs 22.7%).
• No deaths were reported
• No participants were positive for anti-RSLV-132 antibodies.

Efficacy

• There were no significant differences in the mean change in CLASI score, SLEDAI-2K, PGA, and BILAG improvement between the placebo and RSLV-132 groups (Figure 1).

BILAG, British Isles Lupus Assessment Group; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

*Data from Burge, et al.¹

•  In patients with higher SLEDAI score (placebo, n = 9; RSLV-132, n = 13) and CLASI score (placebo, n = 12; RSLV-132, n = 18), the RSLV-132 treated group exhibited increased BICLA, SRI-4, and CLASI-50 responses compared with the placebo group (Figure 2).  

BICLA, British Isles Lupus Assessment Group-based Composite Lupus Assessment; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity Index; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SRI, SLE Responder Index 4.

*Adapted from Burge, et al.¹

 

Key learnings

The safety profile of RSLV-132 was excellent, while the primary endpoint of mean CLASI scores did not show a meaningful difference between the two groups. However, the subgroup of patients with high baseline SLEDAI and CLASI scores demonstrated clinical improvement favoring RSLV-132, indicating that patients with more active systemic disease are most likely to derive clinical benefit from RNase therapy. A key limitation of the study was the small sample size, indicating the need for further larger studies.