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. 2023 May 9:17:1153231.
doi: 10.3389/fnins.2023.1153231. eCollection 2023.

Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)

Thanh G Phan  1   2 , Rebecca Lim  3   4 , Siow T Chan  3   4 , Hannah McDonald  3   4 , Poh-Yi Gan  5   6 , Shenpeng R Zhang  7 , Liz J Barreto Arce  7 , Jason Vuong  1   2 , Tharani Thirugnanachandran  1   2 , Benjamin Clissold  1   2 , John Ly  1   2 , Shaloo Singhal  1   2 , Marie Veronic Hervet  1   2 , Hyun Ah Kim  7 , Grant R Drummond  7 , Euan M Wallace  4   8 , Henry Ma  1   2 , Christopher G Sobey  7
Affiliations

Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)

Thanh G Phan et al. Front Neurosci. .

Erratum in

Abstract

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 × 106/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 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/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 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.

Clinical trial registration: ClinicalTrials.gov, identifier ACTRN12618000076279P.

Keywords: allogeneic; clinical trial; ischemic stroke; phase I; stem cell.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Infarct volume and FLAIR-DWI mismatch: the post-treatment was on the day that the hAEC infusion was completed. For patients receiving a dose of 8 × 106 cells/kg the MRI was on day 2. The unit of hAEC dose was 106 cells/kg. FLAIR, fluid attenuated inversion recovery sequence; DWI, diffusion weighted imaging.
FIGURE 2
FIGURE 2
Hematological profile: there was no particular pattern observed among the eight patients. The unit of hAEC dose was ×106 cells/kg.
FIGURE 3
FIGURE 3
Lymphocyte subset over time: there was no particular pattern observed among the eight patients. The unit of hAEC dose was ×106 cells/kg.
FIGURE 4
FIGURE 4
Inflammatory markers: there was no particular pattern observed among the eight patients. The unit of hAEC dose was ×106 cells/kg.
See this image and copyright information in PMC

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