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

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

doi:10.3389/fnins.2023.1153231

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

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

Authors

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 Zhang⁷, Liz J Barreto Arce⁷, 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 Kim⁷, Grant R Drummond⁷, Euan M Wallace^{4

8}, Henry Ma^{1

2}, Christopher G Sobey⁷

Affiliations

¹ Clinical Trials, Imaging and Informatics Division, Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
² Department of Neurology, Monash Health, Clayton, VIC, Australia.
³ The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
⁴ Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
⁵ Department of Medicine, Centre for Inflammatory Diseases, Monash Medical Centre, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.
⁶ Department of Immunology, Monash Health, Monash Medical Centre, Clayton, VIC, Australia.
⁷ Department of Microbiology, Anatomy, Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia.
⁸ Victorian Department of Health, Melbourne, VIC, Australia.

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.

Grants and funding

This trial was funded by a generous donation from Beluga Foundation and a National Health Medical Research Grant (GNT1163282). The sponsors had no role in the design of the trial or analysis of the results.