by Keyword: Clinical trial

Monteil, V, Eaton, B, Postnikova, E, Murphy, M, Braunsfeld, B, Crozier, I, Kricek, F, Niederhofer, J, Schwarzbock, A, Breid, H, Devignot, S, Klingstrom, J, Thalin, C, Kellner, MJ, Christ, W, Havervall, S, Mereiter, S, Knapp, S, Jimenez, AS, Bugajska-Schretter, A, Dohnal, A, Ruf, C, Gugenberger, R, Hagelkruys, A, Montserrat, N, Kozieradzki, I, Ali, OH, Stadlmann, J, Holbrook, MR, Schmaljohn, C, Oostenbrink, C, Shoemaker, RH, Mirazimi, A, Wirnsberger, G, Penninger, JM, (2022). Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants Embo Molecular Medicine 14, e15230

The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic.

JTD Keywords: Clinical trial, Converting enzyme 2, Covid-19, Spike, Treatment, Vaccine

Mura, A, Maier, M, Ballester, BR, Costa, JD, Lopez-Luque, J, Gelineau, A, Mandigout, S, Ghatan, PH, Fiorillo, R, Antenucci, F, Coolen, T, Chivite, I, Callen, A, Landais, H, Gomez, OI, Melero, C, Brandi, S, Domenech, M, Daviet, JC, Zucca, R, Verschure, PFMJ, (2022). Bringing rehabilitation home with an e-health platform to treat stroke patients: study protocol of a randomized clinical trial (RGS@home) Trials 23, 518

Background: There is a pressing need for scalable healthcare solutions and a shift in the rehabilitation paradigm from hospitals to homes to tackle the increase in stroke incidence while reducing the practical and economic burden for patients, hospitals, and society. Digital health technologies can contribute to addressing this challenge; however, little is known about their effectiveness in at-home settings. In response, we have designed the RGS@home study to investigate the effectiveness, acceptance, and cost of a deep tech solution called the Rehabilitation Gaming System (RGS). RGS is a cloud-based system for delivering Al-enhanced rehabilitation using virtual reality, motion capture, and wearables that can be used in the hospital and at home. The core principles of the brain theory-based RGS intervention are to deliver rehabilitation exercises in the form of embodied, goal-oriented, and task-specific action.; Methods: The RGS@home study is a randomized longitudinal clinical trial designed to assess whether the combination of the RGS intervention with standard care is superior to standard care alone for the functional recovery of stroke patients at the hospital and at home. The study is conducted in collaboration with hospitals in Spain, Sweden, and France and includes inpatients and outpatients at subacute and chronic stages post-stroke. The intervention duration is 3 months with assessment at baseline and after 3, 6, and 12 months. The impact of RGS is evaluated in terms of quality of life measurements, usability, and acceptance using standardized clinical scales, together with health economic analysis. So far, one-third of the patients expected to participate in the study have been recruited (N = 90, mean age 60, days after stroke >= 30 days). The trial will end in July 2023.; Discussion: We predict an improvement in the patients' recovery, high acceptance, and reduced costs due to a soft landing from the clinic to home rehabilitation. In addition, the data provided will allow us to assess whether the prescription of therapy at home can counteract deterioration and improve quality of life while also identifying new standards for online and remote assessment, diagnostics, and intervention across European hospitals.

JTD Keywords: Deep tech, E-health, Functional recovery, Home treatment, Motor recovery, Randomized clinical trial, Stroke, Upper extremities, Virtual reality, Wearables

Monteil V, Dyczynski M, Lauschke VM, Kwon H, Wirnsberger G, Youhanna S, Zhang H, Slutsky AS, Hurtado del Pozo C, Horn M, Montserrat N, Penninger JM, Mirazimi A, (2021). Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection Embo Molecular Medicine 13,

© 2020 The Authors. Published under the terms of the CC BY 4.0 license There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.

JTD Keywords: clinical trial, combination therapy, covid-19, Clinical trial, Combination therapy, Covid-19, Treatment