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A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers
BACKGROUND: Endogenous serine protease inhibitors are associated with anti-inflammatory and pro-survival signaling mediated via Low-density lipoprotein receptor-related protein 1 (LRP1) signaling. SP16 is a short polypeptide that mimics the LRP1 binding portion of alpha-1 antitrypsin. METHODS: A pil...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101931/ https://www.ncbi.nlm.nih.gov/pubmed/33956804 http://dx.doi.org/10.1371/journal.pone.0247357 |
Sumario: | BACKGROUND: Endogenous serine protease inhibitors are associated with anti-inflammatory and pro-survival signaling mediated via Low-density lipoprotein receptor-related protein 1 (LRP1) signaling. SP16 is a short polypeptide that mimics the LRP1 binding portion of alpha-1 antitrypsin. METHODS: A pilot phase I, first-in-man, randomized, double blind, placebo-controlled safety study was conducted to evaluate a subcutaneous injection at three dose levels of SP16 (0.0125, 0.05, and 0.2 mg/kg [up to 12 mg]) or matching placebo in 3:1 ratio in healthy individuals. Safety monitoring included vital signs, laboratory examinations (including hematology, coagulation, platelet function, chemistry, myocardial toxicity) and electrocardiography (to measure effect on PR, QRS, and QTc). RESULTS: Treatment with SP16 was not associated with treatment related serious adverse events. SP16 was associated with mild-moderate pain at the time of injection that was significantly higher than placebo on a 0–10 pain scale (6.0+/-1.4 [0.2 mg/kg] versus 1.5+/-2.1 [placebo], P = 0.0088). No differences in vital signs, laboratory examinations and electrocardiography were found in those treated with SP16 versus placebo. CONCLUSION: A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers. |
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