BIVV020 for Transplant Rejection
Recruiting in Palo Alto (17 mi)
+66 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Sanofi
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing BIVV020, a new drug, to see if it can help prevent or treat a problem called AMR in kidney transplant patients. The drug works by calming the immune system to protect the new kidney.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop your current medications. However, you are expected to receive standard of care (SOC) therapy, so you might continue some existing treatments. Please consult with the trial investigators for specific guidance.
What data supports the idea that BIVV020 for Transplant Rejection is an effective drug?
The available research shows that rituximab, which is similar to BIVV020, has been effective in treating kidney transplant rejection. In one study, 27 patients with severe rejection were treated with rituximab, and only three experienced graft loss. The remaining patients showed significant improvement in kidney function. Another case study highlighted a patient with difficult-to-treat rejection who responded well to rituximab, remaining rejection-free for nine months. These results suggest that BIVV020 could be effective in similar situations.
12345What safety data exists for BIVV020 (Riliprubart) in transplant rejection?
The provided research does not directly mention BIVV020, SAR445088, Riliprubart, or TNT-020. However, it discusses the use of rituximab, a CD20-specific antibody, in transplant rejection. Rituximab has been used in various studies for treating refractory kidney transplant rejection and antibody-mediated rejection. It has shown promise in improving outcomes in severe, steroid-resistant rejection episodes and is considered an important adjunct therapy in desensitization protocols. While these studies focus on rituximab, they may provide indirect insights into the safety and efficacy of similar CD20-targeting therapies like BIVV020.
12467Is the drug BIVV020 a promising treatment for transplant rejection?
Yes, BIVV020, also known as SAR445088, Riliprubart, or TNT-020, is a promising drug for transplant rejection. It is similar to rituximab, which has shown success in treating transplant rejection by targeting specific cells in the immune system. This approach can help prevent the body from attacking the transplanted organ, making it a valuable option for patients.
2891011Eligibility Criteria
This trial is for kidney transplant recipients aged 18-75 with active antibody-mediated rejection (Cohort B), or those about to receive a transplant and are at high risk of rejection (Cohort A). Participants must have a BMI ≤ 40 kg/m2, agree to use contraception, and not be infected with HIV/HCV/HBV or have lupus.Inclusion Criteria
I am a kidney transplant recipient with active antibody-mediated rejection.
Participant Groups
The study tests BIVV020's effectiveness in preventing and treating transplant rejection. It compares standard care treatments like Rituximab, IVIg, Tacrolimus, Corticosteroids, ATG, Mycophenolate with/without the addition of BIVV020.
3Treatment groups
Experimental Treatment
Group I: Standard of Care (SOC) Cohort BExperimental Treatment3 Interventions
SOC includes plasmapheresis, IVIg, corticosteroids, rituximab.
Group II: BIVV020 with Standard of Care (SOC) Cohort BExperimental Treatment4 Interventions
Eligible participants will receive BIVV020 and SOC which includes plasmapheresis, IVIg, corticosteroids, rituximab.
Group III: BIVV020 with Standard of Care (SOC) Cohort AExperimental Treatment4 Interventions
Eligible participants will receive BIVV020 and SOC immunosuppression including induction therapy, tacrolimus, and mycophenolate.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Massachusetts General Hospital Site Number : 8400007Boston, MA
Investigational Site Number : 1240002London, Canada
Cedars-Sinai Medical Center- Site Number : 8400100Los Angeles, CA
University of California San Francisco - Parnassus Heights- Site Number : 8400001San Francisco, CA
More Trial Locations
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Who is running the clinical trial?
SanofiLead Sponsor
References
The emerging role of rituximab in organ transplantation. [2022]Long-term acceptance of solid organ allografts remains a challenge. While many acute rejection episodes can be treated, new mechanisms of allograft damage are now being defined especially in kidney transplantation. Unexpected clusters of CD20(+) cells have been discovered in renal biopsies performed for clinical rejection. C4d deposition is now routinely seen in refractory rejection. Despite the rapid introduction of new immunosuppressive agents in transplantation, the search for an efficacious anti-B-cell agent remains. With novel mechanisms of allograft damage now being defined, it is important to consider how an anti-B-cell agent might fit into an immunosuppressive regimen. Rituximab is a high-affinity CD20 specific antibody that depletes the B-cell compartment by inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell mediated events. In this review, we will discuss the mechanisms of action of rituximab, and its use in for a variety of indications in solid organ transplantation. There are emerging case reports that show that rituximab may be an effective agent to treat antibody-mediated rejection, and post-transplant lymphoproliferative disorder. Rituximab has been frequently cited as an important adjunct therapy in desensitization protocols for highly sensitized transplant recipients as well as recipients of ABO incompatible transplants. Rituximab demonstrates promise in this regard and warrants additional consideration in prospective clinical trials.
Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation. [2019]Data suggest an additional role of T cells in antibody-mediated rejections. In 2001 a protocol for AB0-incompatible kidney transplantation based on B-cell-depleting anti-CD20 antibody rituximab, antigen-specific blood group IgG immunoadsorption, intravenous immunoglobulins, and triple immunosuppression was introduced in Europe, which used induction therapy with the use of interleukin-2 receptor antibody (IL2-RA) basiliximab. We used thymoglobulin in AB0-incompatible patients as induction in the face of high immunologic risk.
Promising new agents in the prevention of transplant rejection. [2018]Promising immunosuppressive drugs designed to prevent rejection have been developed recently. Two monoclonal antibodies directed against the interleukin-2 (IL-2) receptor, daclizumab and basiliximab, have been shown to significantly reduce the incidence of acute rejection without increasing adverse events. Sirolimus (rapamycin), an agent that inhibits T- and B-response at a later stage than cyclosporin, has been shown to be synergistic with cyclosporin in experimental and clinical studies. Ongoing clinical trials have reported that in renal transplantation high doses of sirolimus are as effective as cyclosporin. SDZ-RAD, a derivative of sirolimus, is also under investigation. FTY-720 another promising drug, prolonged the survival of allografts and synergised with cyclosporin and sirolimus in experimental models. Gusperimus (deoxyspergualin), which inhibits IL-1 synthesis, was useful in reversing early and late acute rejection in clinical trials. Antisense oligonucleotides which interfere with intercellular adhesion molecules which are important in rejection, gave encouraging results in primate renal allografts. The availability of these new drugs will be able to further abate the risk of rejection in organ transplantation. However, caution is warranted with their use in order to avoid the risks of over immunosuppression. Today excellent results can be obtained with the available drugs. Newer immunosuppressive schedules should be designed, not only to reduce the risk of rejection, but also to obtain a better therapeutic index that allows a further improvement of the graft survival while minimising the comorbidity and drug-related toxicity.
Rituximab as treatment for refractory kidney transplant rejection. [2023]Recent studies have shown that a high density of CD 20+ cells are seen in patients who have steroid-resistant rejection episodes. Rituximab is a high-affinity CD-20 specific antibody that inhibits B-cell proliferation while inducing cellular apoptosis. Thus, it is a rational choice for therapy in transplantation to abrogate B-cell-mediated events. Twenty-seven patients were diagnosed with biopsy-confirmed rejection manifested by thrombotic microangiopathy and/or endothelialitis between 2/99 and 2/02 at our institution. These individuals were treated with a single dose of rituximab, in addition to other therapies, in an effort to reverse their rejection episodes. Twenty-four received additional steroids while 22 of the 27 patients were also treated with plasmapheresis and antithymocyte globulin (ATG). Only three patients experienced graft loss not associated with patient death during the follow-up period (605 +/- 335.3 days). In the 24 successfully treated patients, the serum creatinine at the time of initiating rituximab therapy was 5.6 +/- 1.0 mg/dL and decreased to 0.95 +/- 0.7 mg/dL at discharge. The addition of rituximab may improve outcomes in severe, steroid-resistant or antibody-mediated rejection episodes after kidney transplantation.
Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab. [2022]Acute rejection is an expected event after transplantation and has been associated with poor long-term kidney transplant outcome. The presence of B cells in the kidney graft with acute rejection is thought to be an omnious sign, as it has been associated with poor graft outcome. There is no definitive treatment for acute rejection with B cells in the graft. Rituximab, a humanized monoclonal antibody against CD20, has been used in the treatment of B cell lymphoma. We present the case of a 49-yr-old Caucasian male with early acute kidney allograft rejection that was refractory to high doses of steroids and rabbit anti-thymocyte globulin (thymoglobulin). Repeat renal biopsy revealed T cell and B cells in the kidney graft and responded to the combination of rituximab and muromonab (a mouse monoclonal antibody to CD3 receptor). Over 9 months post-transplant, the patient remains rejection free with a serum creatinine of 1.7 mg/dL.
[New immunosuppressive therapies in kidney transplantation]. [2021]New approaches to successful prevention and management of transplant rejection include the use of biological immunosuppressants, such as monoclonal antibodies targeting the CD3 and CD4 molecules on native T cells, the interleukin 2 receptor on activated T cells, monocytes and B cells, and adhesion molecules. Several new drugs have been found to be effective immunosuppressive agents: FK 506, a macrolid antibiotic inhibiting lymphokine gene transcription, lymphokine production and secretion, rapamycin, which blocks effects of lymphokine-induced signal transduction, and RS 61443, brequinar and mizoribine, which inhibit DNA/RNA synthesis and lymphocyte proliferation. Initial experience with these drugs clinical protocols currently in use and already devised for use in the near future to test these and other emerging immunosuppressants are reviewed.
Anti-B cell therapy with rituximab as induction therapy in renal transplantation. [2021]Traditionally, antirejection therapy in organ transplantation has mainly been directed at T cells. During recent years, the role of B cells in acute rejection has attracted more attention. In the Radboud University Medical Center (Nijmegen, The Netherlands) we performed a randomized, placebo controlled study to assess the efficacy and safety of rituximab as induction therapy after renal transplantation. In parallel we investigated the effects of rituximab on the numbers and function of B and T cells. An overview of the results, which have largely been published in peer reviewed papers, is presented below.
Treatment of vascular rejection with rituximab in cardiac transplantation. [2015]Vascular rejection is the B-cell-mediated production of immunoglobulin G (IgG) antibody against the transplanted heart. The currently available treatments for vascular rejection have had limited success, and chronic manifestations of vascular rejection require re-transplantation. Rituximab is a monoclonal antibody directed against the CD20 receptor of B-lymphocytes, which is approved for treatment of lymphoma.
Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin. [2022]Rituximab and intravenous Ig (IVIG) are commonly used for desensitization of HLA and blood group-incompatible (ABOi) transplants. However, serious infections have been noted in association with rituximab administration. In this study, we retrospectively compared infectious outcomes in those who received rituximab plus IVIG for HLA or ABOi transplants (RIT group) with a group of nonsensitized, ABO-compatible transplant recipients (non-RIT group).
Polyomavirus BK viremia in kidney transplant recipients after desensitization with IVIG and rituximab. [2015]Desensitization with intravenous immune globulin (IVIG) and rituximab improves transplantation rates. It is unclear if desensitization increases the risk of polyomavirus BK (BKV) viremia. Here, BKV viremia in HLA-sensitized patients after desensitization with IVIG and rituximab was analyzed.
Percentage of CD19+ Cells in Peripheral Blood Lymphocytes After Rituximab-Based Desensitization as a Predictor of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation. [2019]Label="BACKGROUND" NlmCategory="BACKGROUND">Rituximab (RIT) is effective as a part of the desensitization therapy before ABO-incompatible kidney transplantation (ABOi-KTx), and a single dose of RIT at 375 mg/m2 or less is recommended. However, adequate RIT dose recommendations have not yet been established for individual recipients. Therefore, we evaluated the relationship between the proportion of B cells in peripheral blood and acute antibody-mediated rejection (AAMR).