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2024-03-12T13:05:51.000Z

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

Mar 12, 2024
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Learning objective: After reading this article, learners will be able to cite a new clinical development in systemic lupus erythematosus.

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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).

Figure 1. Change from baseline in A CLASI, SLEDAI-2K, PGA, and B BILAG*

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).  

Figure 2. Composite analysis endpoint*

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.

  1. Burge DJ, Werth VP, Boackle SA, et al. Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132. Lupus Sci Med. 2024;11(1):e DOI: 10.1136/lupus-2023-001113

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