BIVV020 for Transplant Rejection

Not currently recruiting at 66 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must not be taking: Complement inhibitors

Disqualifiers: ABO incompatibility, HIV, HBV, HCV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 49 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BIVV020 (also known as SAR445088, Riliprubart, or TNT-020) for individuals who have had or are about to have a kidney transplant. The researchers aim to determine if BIVV020 can prevent or treat antibody-mediated rejection (AMR), a condition where the immune system attacks the new kidney. The trial includes two groups: one for those receiving a new kidney and another for those who have already had a transplant and are experiencing AMR. Individuals with chronic kidney disease undergoing a kidney transplant or current transplant recipients with active AMR might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. It mentions that participants will receive standard of care therapy, which suggests you may continue with some existing treatments, but it's best to discuss this with the trial team.

Is there any evidence suggesting that BIVV020 is likely to be safe for humans?

Research has shown that BIVV020, a treatment for preventing and treating rejection in kidney transplant patients, is under study for its safety and effectiveness. In earlier studies, a single dose of BIVV020 reduced certain immune system activities for up to 15 weeks, helping to protect the transplanted kidney from immune system harm.

These studies reported no major side effects, suggesting that BIVV020 is generally well-tolerated. Participants did not experience severe side effects, indicating a positive safety profile. However, ongoing monitoring is necessary to fully understand any risks associated with new treatments.

As this study is in the middle stage of research, safety data continues to be collected. These findings help ensure the treatment's safety for more people in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for transplant rejection, which typically involves treatments like plasmapheresis, IVIg, corticosteroids, and rituximab, BIVV020 offers a new approach. Researchers are excited about BIVV020 because it targets specific pathways involved in the immune response, potentially reducing the risk of rejection more effectively. Additionally, BIVV020 may provide a more precise intervention, focusing on the underlying mechanisms of rejection rather than just managing symptoms. This focus on targeted action could lead to improved outcomes for patients and a significant advancement in transplant care.

What evidence suggests that BIVV020 might be an effective treatment for transplant rejection?

Research shows that BIVV020, also known as riliprubart, could help manage transplant rejection. In this trial, some participants will receive BIVV020 alongside standard of care (SOC) treatments, which include plasmapheresis, IVIg, corticosteroids, and rituximab, or SOC immunosuppression with induction therapy, tacrolimus, and mycophenolate. Early studies highlight BIVV020's unique mechanism, targeting a part of the immune system that can damage transplanted organs. This treatment aims to prevent and treat antibody-mediated rejection (AMR), a major risk for kidney transplant patients. Initial data suggest BIVV020 is effective in similar conditions, like chronic inflammatory diseases, by reducing immune system attacks. While specific data on transplant rejection is still being gathered, these findings suggest potential benefits for kidney transplant patients dealing with AMR. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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

BMI ≤ 40 kg/m2

Contraceptive use by women during the treatment period, and for at least 49 weeks after the last administration of IMP (BIVV020 + SOC arm participant) or last treatment period visit (SOC arm participant)

I have chronic kidney disease and will get a kidney transplant.

Exclusion Criteria

Participants with known active ongoing infection including: Positive HIV, Positive HBV, HCV with detectable HCV RNA, Within 4 weeks of first study intervention: any serious infection, or any active bacterial infection, or any other infection which is clinically significant in the opinion of the Investigator, unless it can be confirmed that infection was cleared at least 3 days prior to first study intervention, History of active tuberculosis (TB) regardless of treatment, Participants with clinical diagnosis of systemic lupus erythematosus (SLE), Prior treatment with complement system inhibitor within 5 times the half-life, Current enrollment in any other clinical study where the last investigational study treatment administration was within 5 half-lives from study intervention initiation

Participants who are ABO incompatible with their donors

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BIVV020 and Standard of Care (SOC) for prevention or treatment of AMR

49 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

22 weeks

Long-term follow-up

Participants are monitored for adverse events and pharmacokinetic parameters

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• BIVV020

Trial Overview 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.

How Is the Trial Designed?

Group I: Standard of Care (SOC) Cohort B Experimental Treatment 3 Interventions

SOC includes plasmapheresis, IVIg, corticosteroids, rituximab.

Group II: BIVV020 with Standard of Care (SOC) Cohort B Experimental Treatment 4 Interventions

Eligible participants will receive BIVV020 and SOC which includes plasmapheresis, IVIg, corticosteroids, rituximab.

Group III: BIVV020 with Standard of Care (SOC) Cohort A Experimental Treatment 4 Interventions

Eligible participants will receive BIVV020 and SOC immunosuppression including induction therapy, tacrolimus, and mycophenolate.

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

Desensitization with IVIG and rituximab in HLA-sensitized transplant patients is linked to a higher incidence of polyomavirus BK (BKV) viremia, with 20% of desensitized patients experiencing viremia compared to 10% in non-desensitized patients by 2 years post-transplant.

Despite the increased viremia in the desensitized group, there was no significant difference in BKV-associated nephropathy or graft loss, indicating that while desensitization raises the risk of BKV viremia, it does not necessarily lead to worse transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyomavirus BK viremia in kidney transplant recipients after desensitization with IVIG and rituximab. Barbosa, D., Kahwaji, J., Puliyanda, D., et al.[2015]

Rituximab, a CD20-specific antibody, shows potential as an effective treatment for antibody-mediated rejection in kidney transplantation by depleting B-cells, which are implicated in new mechanisms of allograft damage.

Emerging case reports suggest that rituximab may also be beneficial in desensitization protocols for highly sensitized transplant recipients and those receiving ABO incompatible transplants, indicating its importance in improving transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of rituximab in organ transplantation. Becker, YT., Samaniego-Picota, M., Sollinger, HW.[2022]

In a study of 361 kidney transplant patients, the use of rituximab combined with intravenous Ig (IVIG) for desensitization did not increase the risk of infections compared to nonsensitized, ABO-compatible transplant recipients.

Both groups had similar rates of bacterial, viral, and serious infections, indicating that rituximab is a safe option for patients undergoing HLA or ABO-incompatible transplants without compromising their infection outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin. Kahwaji, J., Sinha, A., Toyoda, M., et al.[2022]

In a study of 44 kidney transplant recipients, those with a higher percentage of B cells (%CD19 > 1.2%) before transplantation had a significantly increased risk of acute antibody-mediated rejection (AAMR) compared to those with lower levels (%CD19 ≤ 1.2%).

The study suggests that monitoring %CD19 levels after rituximab treatment can help predict the risk of AAMR, indicating that insufficient depletion of B cells may lead to transplant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hirose, T., Iwami, D., Hotta, K., et al.[2019]

Rituximab, a monoclonal antibody targeting B-lymphocytes, was administered to 8 patients with vascular rejection after heart transplantation, resulting in a return of left ventricular ejection fraction (LVEF) to baseline levels and complete resolution of rejection markers in biopsies.

The treatment was well-tolerated, with no significant infections or drug-related complications reported, suggesting that rituximab may be a safe and effective option for managing vascular rejection in heart transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of vascular rejection with rituximab in cardiac transplantation. Garrett, HE., Duvall-Seaman, D., Helsley, B., et al.[2015]

In a study of 9 AB0-incompatible kidney transplant recipients, thymoglobulin induction therapy resulted in immediate graft function without significant differences in graft function, rejection rates, or infections compared to 36 AB0-compatible recipients receiving different induction therapies.

Thymoglobulin was found to have a safety and efficacy profile similar to that of IL-2 receptor antagonists like basiliximab, suggesting it can be a viable option for high immunologic risk patients in kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation. Herzog, AL., Kalogirou, C., Wanner, C., et al.[2019]

New biological immunosuppressants, including monoclonal antibodies targeting specific T cell molecules and interleukin receptors, show promise in preventing transplant rejection by effectively modulating the immune response.

Several novel drugs, such as FK 506 and rapamycin, have been identified as effective immunosuppressants, each working through different mechanisms like inhibiting lymphokine production or blocking signal transduction, which are crucial for lymphocyte activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New immunosuppressive therapies in kidney transplantation]. Pomer, S.[2021]

A 49-year-old male with acute kidney transplant rejection that did not respond to standard treatments showed improvement after receiving a combination of rituximab and muromonab, indicating a potential new treatment strategy for acute rejection involving B cells.

The patient remained rejection-free for 9 months post-transplant, suggesting that this combination therapy may enhance long-term graft survival in cases of acute rejection with B cell involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab. Alausa, M., Almagro, U., Siddiqi, N., et al.[2022]

In a study of 27 kidney transplant patients with severe, steroid-resistant rejection, treatment with rituximab led to significant improvements in kidney function, as indicated by a decrease in serum creatinine levels from 5.6 mg/dL to 0.95 mg/dL at discharge.

Only three patients experienced graft loss not related to patient death during a follow-up period of about 605 days, suggesting that rituximab may effectively help reverse rejection episodes and improve transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab as treatment for refractory kidney transplant rejection. Becker, YT., Becker, BN., Pirsch, JD., et al.[2023]

A randomized, placebo-controlled study at Radboud University Medical Center evaluated the efficacy and safety of rituximab as an induction therapy for kidney transplantation, highlighting the growing importance of targeting B cells in preventing organ rejection.

The study also examined how rituximab affects the numbers and functions of both B and T cells, suggesting a potential shift in antirejection strategies beyond traditional T cell-focused therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-B cell therapy with rituximab as induction therapy in renal transplantation. Joosten, I., Baas, MC., Kamburova, EG., et al.[2021]

Monoclonal antibodies like daclizumab and basiliximab effectively reduce acute rejection in organ transplants without increasing adverse events, highlighting their safety and efficacy.

New immunosuppressive drugs, such as sirolimus and FTY-720, show promise in enhancing graft survival and can work synergistically with existing treatments, but careful management is needed to prevent over immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising new agents in the prevention of transplant rejection. Ponticelli, C., Tarantino, A.[2018]

Citations

1. researchgate.net researchgate.net/publication/379719106_Preliminary_Efficacy_and_Safety_Data_from_the_Phase_2_Trial_of_Riliprubart_SAR445088_a_Humanized_Monoclonal_Antibody_Targeting_Complement_C1s_in_Chronic_Inflammatory_Demyelinating_Polyneuropathy_CIDP_

Preliminary Efficacy and Safety Data from the Phase 2 Trial ... Positive preliminary results of a phase 2 trial determining the efficacy and safety of riliprubart in the treatment of CIDP were presented at ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05156710

Study Details | NCT05156710 | BIVV020 (SAR445088) n ... A multi-cohort, randomized, phase 2, open-label study to assess the preliminary efficacy, safety, and pharmacokinetics of BIVV020 for prevention and treatment ...

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-riliprubart-for-preventing-and-treating-antibody-mediated-rejection-in-adult-kidney-transplant-patients/

Study on Riliprubart for Preventing and Treating Antibody ... The purpose of the study is to evaluate how effective and safe BIVV020 is in managing transplant rejection. Participants in the study will ...

4. news.sanofi.us news.sanofi.us/2025-06-25-Riliprubart-earns-orphan-drug-designation-in-the-US-for-antibody-mediated-rejection-in-solid-organ-transplantation

Riliprubart earns orphan drug designation in the ... Antibody mediated rejection represents a serious threat to transplanted organs and patient survival. Through riliprubart's innovative mechanism ...

5. withpower.com withpower.com/trial/phase-2-11-2021-6aabf

BIVV020 for Transplant Rejection · Info for Participants The available research shows that rituximab, which is similar to BIVV020, has been effective in treating kidney transplant rejection. In one study, 27 patients ...

6. sanofistudies.com sanofistudies.com/cwout/CW-V9DEXS//us/en/listing/290643/bivv020-in-prevention-and/

BIVV020 in Prevention and Treatment of Antibody ... This study investigates the use of an investigational medication in patients who have undergone or are about to undergo a kidney transplant and may experience ...

7. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-06-25-05-00-00-3104793

Press Release: Riliprubart earns orphan drug designation ... Antibody mediated rejection represents a serious threat to transplanted organs and patient survival. Through riliprubart's innovative mechanism ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123076723

Classical Complement Inhibition By SAR445088 (BIVV020 ... A single IV dose of SAR445088 led to classical complement inhibition, control of hemolysis, and improvement in anemia, which was sustained for 15 weeks.