BIVV020 for Transplant Rejection

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

48 Participants Needed

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.

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.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug BIVV020 for transplant rejection?

Rituximab, a drug similar to BIVV020, has shown promise in treating transplant rejection by targeting B-cells, which are involved in the rejection process. Studies have reported that rituximab can improve outcomes in severe, steroid-resistant rejection episodes after kidney transplantation. ^{1 2 3 4 5}

What 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. ^{1 2 4 6 7}

Is 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. ^{2 8 9 10 11}

How is the drug BIVV020 different from other treatments for transplant rejection?

BIVV020 is unique because it targets a specific part of the immune system involved in transplant rejection, potentially offering a new approach compared to existing treatments like rituximab, which targets B-cells. This could provide an alternative for patients who do not respond well to current therapies. ^{2 8 9 10 11}

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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 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]

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 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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The emerging role of rituximab in organ transplantation. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Induction Therapy With Thymoglobulin in AB0-Incompatible Kidney Transplantation. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Promising new agents in the prevention of transplant rejection. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Rituximab as treatment for refractory kidney transplant rejection. [2023]

5. Denmark pubmed.ncbi.nlm.nih.gov

Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

[New immunosuppressive therapies in kidney transplantation]. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Anti-B cell therapy with rituximab as induction therapy in renal transplantation. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Treatment of vascular rejection with rituximab in cardiac transplantation. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Polyomavirus BK viremia in kidney transplant recipients after desensitization with IVIG and rituximab. [2015]

11. United States 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. [2019]