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Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)
BACKGROUND: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. METHODS: The design is based on 3 + 3 dose escalation design with additional components for...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204798/ https://www.ncbi.nlm.nih.gov/pubmed/37229431 http://dx.doi.org/10.3389/fnins.2023.1153231 |
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author | Phan, Thanh G. Lim, Rebecca Chan, Siow T. McDonald, Hannah Gan, Poh-Yi Zhang, Shenpeng R. Barreto Arce, Liz J. Vuong, Jason Thirugnanachandran, Tharani Clissold, Benjamin Ly, John Singhal, Shaloo Hervet, Marie Veronic Kim, Hyun Ah Drummond, Grant R. Wallace, Euan M. Ma, Henry Sobey, Christopher G. |
author_facet | Phan, Thanh G. Lim, Rebecca Chan, Siow T. McDonald, Hannah Gan, Poh-Yi Zhang, Shenpeng R. Barreto Arce, Liz J. Vuong, Jason Thirugnanachandran, Tharani Clissold, Benjamin Ly, John Singhal, Shaloo Hervet, Marie Veronic Kim, Hyun Ah Drummond, Grant R. Wallace, Euan M. Ma, Henry Sobey, Christopher G. |
author_sort | Phan, Thanh G. |
collection | PubMed |
description | BACKGROUND: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. METHODS: The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 10(6)/kg, i.v.) on preventing immunosuppression after stroke. RESULTS: Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 10(6) cells/kg (2 × 10(6)/kg, n = 3; 4 × 10(6)/kg, n = 3; 8 × 10(6)/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload. CONCLUSION: Our Phase I trial demonstrates that a maximal dose of 2 × 10(6)/kg hAECs given intravenously each day over 2 days (a total of 4 × 10(6)/kg) is safe and optimal for use in a Phase II trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier ACTRN12618000076279P. |
format | Online Article Text |
id | pubmed-10204798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102047982023-05-24 Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) Phan, Thanh G. Lim, Rebecca Chan, Siow T. McDonald, Hannah Gan, Poh-Yi Zhang, Shenpeng R. Barreto Arce, Liz J. Vuong, Jason Thirugnanachandran, Tharani Clissold, Benjamin Ly, John Singhal, Shaloo Hervet, Marie Veronic Kim, Hyun Ah Drummond, Grant R. Wallace, Euan M. Ma, Henry Sobey, Christopher G. Front Neurosci Neuroscience BACKGROUND: We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial. METHODS: The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 10(6)/kg, i.v.) on preventing immunosuppression after stroke. RESULTS: Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 10(6) cells/kg (2 × 10(6)/kg, n = 3; 4 × 10(6)/kg, n = 3; 8 × 10(6)/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload. CONCLUSION: Our Phase I trial demonstrates that a maximal dose of 2 × 10(6)/kg hAECs given intravenously each day over 2 days (a total of 4 × 10(6)/kg) is safe and optimal for use in a Phase II trial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier ACTRN12618000076279P. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10204798/ /pubmed/37229431 http://dx.doi.org/10.3389/fnins.2023.1153231 Text en Copyright © 2023 Phan, Lim, Chan, McDonald, Gan, Zhang, Barreto Arce, Vuong, Thirugnanachandran, Clissold, Ly, Singhal, Hervet, Kim, Drummond, Wallace, Ma and Sobey. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Phan, Thanh G. Lim, Rebecca Chan, Siow T. McDonald, Hannah Gan, Poh-Yi Zhang, Shenpeng R. Barreto Arce, Liz J. Vuong, Jason Thirugnanachandran, Tharani Clissold, Benjamin Ly, John Singhal, Shaloo Hervet, Marie Veronic Kim, Hyun Ah Drummond, Grant R. Wallace, Euan M. Ma, Henry Sobey, Christopher G. Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title | Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title_full | Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title_fullStr | Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title_full_unstemmed | Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title_short | Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT) |
title_sort | phase i trial outcome of amnion cell therapy in patients with ischemic stroke (i-act) |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204798/ https://www.ncbi.nlm.nih.gov/pubmed/37229431 http://dx.doi.org/10.3389/fnins.2023.1153231 |
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