Clinical Trials Logo

Clinical Trial Summary

An open-label, 56 day, single-center, exploratory, proof-of-concept study of the anti-viral effect of voclosporin (VCS) with an extended safety follow-up, up to 1 year. Study population are adult KTRs with positive SARS-CoV-2 infection with mild to moderate symptoms. At study entry, subjects are on standard therapy of dual immunosuppressive treatment of prednisone and tacrolimus (TAC), following randomization, 10 out of 20 subjects will remain on this therapy for the duration of the study, while the other 10 subjects will switch to VCS.


Clinical Trial Description

Calcineurin inhibitors (CNIs) are general immunosuppressive agents commonly used in the setting of transplantation to prevent solid organ rejection. CNIs form the cornerstone of immunosuppressive treatment in kidney transplant recipients (KTRs) including the 1st generation CNI Cyclosporin-A (CsA) and the most commonly employed 2nd generation CNI tacrolimus (TAC). It is of interest that CNIs, especially CsA, also exert anti-viral effects in addition to immunosuppressive effects. Common side effects of CNIs are hypertension, new-onset diabetes, renal insufficiency and neurotoxicity. Therefore, in the recent decennium, efforts have been directed at developing a novel CNI, voclosporin (VCS), that has improved pharmacodynamic (PD) and pharmacokinetic (PK) attributes with respect to calcineurin inhibition as well as an improved safety profile to common side effects. VCS has been extensively studied in KTRs demonstrating equivalent efficacy to TAC with respect to prevention of rejection while showing a reduction in CNI-related toxicity. Most recently, VCS as a component of multitargeted therapy demonstrated superior efficacy compared to standard of care in lupus nephritis (LN) patients. In 2011, a pivotal study from Leiden University Medical Center (LUMC) demonstrated in vitro anti-viral effect of CsA on Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1). Subsequently, VCS has been shown to have a more potent anti-viral effect on norovirus compared to CsA. The anti-viral effects of CNIs have a different mechanism of inhibition in each virus but mainly through inhibiting cyclophilins, an essential protein for viral replication. The SARS-CoV-1 interacts with human cyclophilins, however the role of these proteins in infection remains elusive. Different reports stablished interactions between nsp1 or nucleocapsid proteins with Cyps and hypothesize its influence in viral replication and viral entry. Unlike VCS and CsA, TAC binds to FK binding proteins rather than cyclophilin A (CypA). Given the current COVID-19 pandemic, the LUMC has very recently demonstrated anti-viral effects of CNIs on SARS-CoV-2 infected cells in vitro: a 2-log reduction of SARS-CoV-2 viral titers in Calu-3 2B4 bronchial cell cultures was observed when incubated with ~3 μM VCS compared to 25μM CsA and 25μM TAC. In each experiment Remdesivir was taken as positive control as it inhibits viral replication by >4log at 10 μM concentration. As such, VCS becomes an attractive and potentially feasible CNI to use or switch to in COVID-19 infected KTRs who are already using CNIs as part of their chronic immunosuppressive therapy. Because subjects will be randomized to either VCS or TAC as immunosuppressive agent during COVID-19 infection, the burden of the study is two-fold: first, subjects will need to switch to a novel CNI which intrinsically will harbour an uncertainty. However, from a clinical point-of-view VCS is proven equivalent to TAC with respect to organ rejection and safety monitoring of adequate drug levels is incorporated in the study. Secondly, subjects will need to agree to self-assessments including monitoring of vital signs and collection of saliva samples and a throat swab in the first 56 days. We believe that it is actually in the interest of subjects to undergo this intensive monitoring because current standard practice is for KTRs with mild symptoms to not be hospitalized and stay at home until recovery without further monitoring. In addition, blood sampling (10 x 38.5 mL), urine sampling and additional hospital visits will take place which are outside of normal clinical practice. The potential advantage of the study to KTRs is that VCS may lead to a quicker reduction of SARS-CoV-2 viral load and quicker relief of symptoms. Altogether, we believe the burden of the study is minimal and outweighed by the potential benefit of the treatment on COVID-19 infection. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04701528
Study type Interventional
Source Leiden University Medical Center
Contact Y.K.O. Teng, MD, PhD
Phone +31-(0)71-5262148
Email y.k.o.teng@lumc.nl
Status Recruiting
Phase Phase 2
Start date November 15, 2020
Completion date October 25, 2022

See also
  Status Clinical Trial Phase
Completed NCT05047692 - Safety and Immunogenicity Study of AdCLD-CoV19-1: A COVID-19 Preventive Vaccine in Healthy Volunteers Phase 1
Recruiting NCT04395768 - International ALLIANCE Study of Therapies to Prevent Progression of COVID-19 Phase 2
Completed NCT04506268 - COVID-19 SAFE Enrollment N/A
Completed NCT04508777 - COVID SAFE: COVID-19 Screening Assessment for Exposure
Terminated NCT04555096 - A Trial of GC4419 in Patients With Critical Illness Due to COVID-19 Phase 2
Completed NCT04961541 - Evaluation of the Safety and Immunogenicity of Influenza and COVID-19 Combination Vaccine Phase 1/Phase 2
Active, not recruiting NCT04546737 - Study of Morphological, Spectral and Metabolic Manifestations of Neurological Complications in Covid-19 Patients N/A
Terminated NCT04542993 - Can SARS-CoV-2 Viral Load and COVID-19 Disease Severity be Reduced by Resveratrol-assisted Zinc Therapy Phase 2
Completed NCT04494646 - BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19) Phase 2
Completed NCT04532294 - Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/COVID-19) Neutralizing Antibody in Healthy Participants Phase 1
Terminated NCT04581915 - PHRU CoV01 A Trial of Triazavirin (TZV) for the Treatment of Mild-moderate COVID-19 Phase 2/Phase 3
Not yet recruiting NCT04543006 - Persistence of Neutralizing Antibodies 6 and 12 Months After a Covid-19 N/A
Completed NCT04507867 - Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III N/A
Completed NCT04387292 - Ocular Sequelae of Patients Hospitalized for Respiratory Failure During the COVID-19 Epidemic N/A
Not yet recruiting NCT04527211 - Effectiveness and Safety of Ivermectin for the Prevention of Covid-19 Infection in Colombian Health Personnel Phase 3
Completed NCT04537663 - Prevention Of Respiratory Tract Infection And Covid-19 Through BCG Vaccination In Vulnerable Older Adults Phase 4
Not yet recruiting NCT05038449 - Study to Evaluate the Efficacy and Safety of Colchicine Tablets in Patients With COVID-19 N/A
Completed NCT04979858 - Reducing Spread of COVID-19 in a University Community Setting: Role of a Low-Cost Reusable Form-Fitting Fabric Mask N/A
Completed NCT04610502 - Efficacy and Safety of Two Hyperimmune Equine Anti Sars-CoV-2 Serum in COVID-19 Patients Phase 2
Active, not recruiting NCT06042855 - ACTIV-6: COVID-19 Study of Repurposed Medications - Arm G (Metformin) Phase 3