Clinical Research Directory

Is Valacyclovir Non-inferior to Valganciclovir as CMV and EBV Prophylaxis in Kidney Transplant Recipients? A Single-Center Prospective Randomized Pilot Study

Opportunistic CMV viremia (primary infection or reactivation) is usually managed by taking prophylactic medication for both adult and pediatric kidney transplant patients. Most hospitals prescribe valganciclovir for this purpose but valacyclovir has also been used. The most unfavorable side effect of valganciclovir is bone marrow suppression which can be troublesome for kidney transplant patients who are already immunosuppressed. We aim to assess the non-inferiority of valacyclovir compared with valganciclovir in this study.

Zuberitamab for EBV Infection Post-Allo-HSCT

EBV DNAemia is defined as the presence of EBV-DNA load in peripheral blood exceeding the normal threshold, serving as a key diagnostic indicator for EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD). According to the European Conference on Infections in Leukemia (ECIL-6) guidelines, regular monitoring of peripheral blood EBV-DNA levels via quantitative real-time PCR (qPCR) is recommended starting from the first month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a weekly frequency sustained for at least 4 months post-transplant. For HSCT patients who develop EBV DNAemia, preemptive therapy should be initiated promptly. EBV-PTLD is a serious complication that may progress rapidly; if not diagnosed and treated in a timely manner, mortality rates can reach 60-80%. Current guidelines recommend CD20 monoclonal antibody (rituximab) as the first-line preemptive treatment. The response rate to rituximab is approximately 84%. The typical regimen consists of 375 mg/m² per dose, administered weekly, with 1-4 doses generally sufficient to achieve treatment goals. However, a subset of patients exhibits poor response to first-line therapy and requires second-line interventions, such as EBV-specific cytotoxic T lymphocytes (EBV-CTLs), donor lymphocyte infusion, or combination chemotherapy. Zuberitamab is a novel anti-CD20 monoclonal antibody and the first Class 1 innovative biologics targeting CD20 developed in China. Preclinical studies have demonstrated that zuberitamab exhibits stronger antibody-dependent cellular cytotoxicity (ADCC) activity compared to rituximab. In a pivotal Phase III registrational clinical study, zuberitamab combined with CHOP (Hi-CHOP) was evaluated head-to-head against R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL). The results showed an improvement in the complete response (CR) rate by more than 8% (85.7% vs. 77.3%, P = 0.038). These findings indicate that zuberitamab holds significant advantages over rituximab in terms of both biological activity and clinical efficacy. Based on this evidence, we have initiated a Phase II clinical trial to evaluate the efficacy and safety of zuberitamab as first-line preemptive therapy for EBV infection. This is a prospective Phase II clinical trial enrolling patients with EBV infection following transplantation. Zuberitamab will be administered as first-line preemptive therapy.

Multivirus-specific T-cell Transfer Post SCT vs AdV, CMV and EBV Infections

Haematopoietic stem cell transplantation (HSCT) can expose patients to a transient but marked immunosuppression, during which viral infections are an important cause of morbidity and mortality. Adoptive transfer of virus-specific T cells is an attractive approach to restore protective T-cell immunity in patients with refractory viral infections after allogeneic HSCT. The aim of this Phase III trial is to confirm efficacy of this treatment in children and adults.

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation

The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

Investigating Epstein-Barr Virus Associated Conjunctivitis

Conjunctivitis means inflammation of the conjunctiva, the thin transparent layer over the white of the eye and under the eyelids. Acute conjunctivitis caused by infection is the most common condition seen in ophthalmic emergency departments, accounting for up to 10% of cases. It is responsible for 41% of eye-related general practice consultations. A diagnosis is usually made on the patient's symptoms and signs, despite this being less reliable than laboratory testing. When a cause is found, it is usually a common cold virus called adenovirus, that gets better with time and does not require treatment. Through investigating cases of conjunctivitis at Moorfields, it has been discovered that in addition to adenovirus, Epstein Barr virus (EBV) is sometimes detected in conjunctival swabs from individuals with conjunctivitis. EBV is a very common viral infection that 95% of adults have experienced. EBV infection mostly passes unnoticed but when symptoms do occur, they include a sore throat, high temperature, swollen glands and tiredness, often called glandular fever or infectious mononucleosis. Conjunctivitis can also occur. EBV remains in the body after infection and rarely causes further problems. The virus can become active again occasionally, which is known as reactivation. Reactivation usually passes unnoticed but sometimes is associated with recurrence of symptoms. It is possible that reactivation may cause conjunctivitis. It is not certain, which is will be observed as a part of this study, as it might be the cause of some of the conjunctivitis seen. Through a collaboration with University College London (UCL), the aim is to gain further insight into infectious conjunctivitis, particularly in relation to EBV. This will be done by taking a swab of the conjunctiva, a single blood test and a tiny (1-2mm) tissue sample from the inner eyelid. Improved knowledge will allow the research team to develop better guidance and treatment for patients with conjunctivitis.

Study to Evaluate the Efficacy of 2LEBV® and 2LXFS® on Asthenia in Patients With an Epstein-Barr Virus Infection

Worldwide, 95% of adults are infected with Epstein-Barr Virus (EBV). These infections may cause different diseases. In most cases, EBV infection is asymptomatic because of a highly effective host immune response. Some individuals develop infectious mononucleosis (a self-limiting lymphoproliferative disorder in adolescents and young adults that is considered to be the primary infection), while others develop chronic fatigue syndrome, EBV-associated lymphoid, or epithelial malignancies. Today, there is no available treatment to treat and destroy EBV. The treatment is essentially symptomatic (treatment of the symptoms and not of the virus itself) with analgesics for pain for example. The studied drugs are 2LEBV® and 2LXFS®, from Labo'Life company, and the treatment schema is the same for the two drugs: it consists in taking the content of one capsule per day, sequentially, according to capsules' numerical order: 1 through 10. When capsule number 10 is taken, capsule 1 of the next blister should be taken on the next day to continue the treatment. The duration of treatment will be of 6 months of continuous intake of the content of 1 capsule/day. The aim of this study is to provide additional information on effectiveness on the 2LEBV® and 2LXFS®in the treatment of EBV chronic and acute infections, and in particular to demonstrate their effectiveness versus placebo in the reduction of asthenia and other symptoms in EBV infection.

Clinical Study of EBV-TCR-T Cells for EBV-associated Hemophagocytic Lymphohistiocytosis or EBV Infection

This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of EBV-TCR-T cell immunotherapy in treating EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) or EBV infection

Surveillance and Tracking the Outcomes of Chronic Latent EBV Infection

Immunocompetent subjects with high load of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood will be enrolled and prospectively followed up to track the natural histories of the chronic high load of EBV virus. The primary goal of this study is to explore the association of peripheral high load of EBV with the hematological malignancies, and second goal is to investigate the genetic mechanisms of immune escape and tumorigenesis of chronic EBV infection.