A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers.
<h4>Background</h4>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 antitryp...
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247357&type=printable |
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| author | George F Wohlford Leo F Buckley Dinesh Kadariya Taeshik Park Juan Guido Chiabrando Salvatore Carbone Virginia Mihalick Matthew S Halquist Adam Pearcy Dana Austin Cohava Gelber Antonio Abbate Benjamin Van Tassell |
| author_facet | George F Wohlford Leo F Buckley Dinesh Kadariya Taeshik Park Juan Guido Chiabrando Salvatore Carbone Virginia Mihalick Matthew S Halquist Adam Pearcy Dana Austin Cohava Gelber Antonio Abbate Benjamin Van Tassell |
| author_sort | George F Wohlford |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers. |
| format | Article |
| id | doaj-art-09cf899d9c1a4cfdb253d9f03f50cf57 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-09cf899d9c1a4cfdb253d9f03f50cf572025-01-18T05:31:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e024735710.1371/journal.pone.0247357A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers.George F WohlfordLeo F BuckleyDinesh KadariyaTaeshik ParkJuan Guido ChiabrandoSalvatore CarboneVirginia MihalickMatthew S HalquistAdam PearcyDana AustinCohava GelberAntonio AbbateBenjamin Van Tassell<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>A one-time treatment with SP16 for doses up to 0.2 mg/kg or 12 mg was safe in healthy volunteers.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247357&type=printable |
| spellingShingle | George F Wohlford Leo F Buckley Dinesh Kadariya Taeshik Park Juan Guido Chiabrando Salvatore Carbone Virginia Mihalick Matthew S Halquist Adam Pearcy Dana Austin Cohava Gelber Antonio Abbate Benjamin Van Tassell A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. PLoS ONE |
| title | A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. |
| title_full | A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. |
| title_fullStr | A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. |
| title_full_unstemmed | A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. |
| title_short | A phase 1 clinical trial of SP16, a first-in-class anti-inflammatory LRP1 agonist, in healthy volunteers. |
| title_sort | phase 1 clinical trial of sp16 a first in class anti inflammatory lrp1 agonist in healthy volunteers |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0247357&type=printable |
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