Anti-CD38 monoclonal antibody CM313 for systemic lupus erythematosus: a randomized, double-blind, placebo-controlled phase Ib/IIa trial 2025 Zhao

J

Jaybee00

Senior Member (Voting Rights)

Abstract​

CD38 is highly expressed on various immune cells, including long-lived plasma cells, making it a potential therapeutic target in autoimmune diseases. This phase Ib/IIa study aimed to explore the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CM313, an anti-CD38 antibody, in patients with systemic lupus erythematosus (SLE). Eligible patients were sequentially enrolled in four ascending dose groups (2, 4, 8, and 16 mg/kg) and randomized 4:1 to receive CM313 or placebo intravenously at days 1, 29, 36, 43, and 50. The primary endpoint was safety, and efficacy was exploratorily investigated. Between October 14, 2022, and March 7, 2024, 40 patients were enrolled, including 8 patients in each CM313 dose group and the pooled placebo group. Adverse events occurred in 90.6% and 62.5% of participants receiving CM313 and placebo, all of which were mild or moderate. Upper respiratory tract infection (87.5%/62.5% vs. 12.5%), urinary tract infection (12.5%/25.0% vs. 0), and herpes zoster (25.0%/0 vs. 0) were more frequent in CM313 8 and 16 mg/kg groups than the placebo group. The CM313 groups had greater reductions in anti-ds-DNA antibodies, immunoglobulin G (IgG), IgA, IgM, IgE, and greater increases in complement C3 and C4 compared with placebo. Systemic Lupus Erythematosus Responder Index-4 response rates were 33.3%, 40.0%, 62.5%, 71.4%, and 37.5% in CM313 2, 4, 8, 16 mg/kg, and placebo groups at day 57, respectively. CM313 showed a manageable safety profile in SLE patients at 2–16 mg/kg and encouraging clinical efficacy at 8 and 16 mg/kg. The results support further investigation of CM313 for treating SLE patients (ClinicalTrials.gov ID: NCT05465707).

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Anti-CD38 monoclonal antibody CM313 for systemic lupus erythematosus: a randomized, double-blind, placebo-controlled phase Ib/IIa trial - Signal Transduction and Targeted Therapy

CD38 is highly expressed on various immune cells, including long-lived plasma cells, making it a potential therapeutic target in autoimmune diseases. This phase Ib/IIa study aimed to explore the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CM313, an anti-CD38 antibody...
www.nature.com www.nature.com
 
The placebo group actually looks quite good:

Fig. 3
figure 3
SRI-4 response rate and improvement in SELENA-SLEDAI score.

a The proportion of patients achieving a Systemic Lupus Erythematosus Responder Index (SRI)-4 response, defined as a ≥ 4-point reduction from baseline (BL) in the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score, no new disease activity as measured by one A score or two B scores on the British Isles Lupus Assessment Group 2004 index (BILAG-2004), and a < 0.3-point increase in the Physician’s Global Assessment (PGA) score.

Missing data was imputed by the last observation carried forward method. N indicates the number of evaluable patients, defined as those with a SELENA-SLEDAI score ≥4, not all A scores in all organ domains on BILAG-2004, and a PGA score ≤2.7 at baseline.

b Mean change from baseline in SELENA-SLEDAI score. Error bars denote standard errors. All patients enrolled were evaluable.

c The proportion of patients achieving a ≥ 4-point reduction in SELENA-SLEDAI score from baseline. N indicates the number of evaluable patients, defined as those with a SELENA-SLEDAI score ≥4 at baseline
 
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