BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR)

Study Overview
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Brief Summary
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Primary Objectives: Cohort A: To evaluate the efficacy of BIVV020 in prevention of AMR Cohort B: To evaluate the efficacy of BIVV020 in treatment of active AMR Secondary Objectives: To assess the overall efficacy of BIVV020 in prevention or treatment of AMR To characterize the safety and tolerability of BIVV020 in kidney transplant participants To characterize the pharmacokinetic (PK) profile of BIVV020 in kidney transplant participants To evaluate the immunogenicity of BIVV020

Detailed Description
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Up to approximately 2 years

Official Title
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A Multi-cohort, Randomized, Phase 2, Open-label Study to Assess the Preliminary Efficacy, Safety, and Pharmacokinetics of BIVV020 for Prevention and Treatment of Antibody-mediated Rejection in Adult Kidney Transplant Recipients.

Conditions
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Transplant Rejection

Intervention / Treatment
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* Drug: BIVV020 (SAR445088)
* Drug: Intravenous immunoglobulin (IVIg)
* Drug: Rituximab or biosimilar
* Drug: Antithymocyte globulin (ATG)
* Drug: Tacrolimus
* Drug: Mycophenolate
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Participant intended to receive SOC therapy per Investigator's judgment and local practice. Cohort A: Participants with chronic kidney disease who will receive a kidney transplant from a living or deceased donor. Cohort B: Participants who are kidney transplant recipients diagnosed with active AMR. 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). Contraceptive use by men 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). Exclusion Criteria: Participants who are ABO incompatible with their donors. Participants with known active ongoing infection as per below: 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 option 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. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIVV020 with Standard of Care (SOC) Cohort A<br>Eligible participants will receive BIVV020 and SOC immunosuppression including induction therapy, tacrolimus, and mycophenolate. | Drug: BIVV020 (SAR445088)<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Antithymocyte globulin (ATG)<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Tacrolimus<br>* Pharmaceutical Form: Tablet Route of Administration: Oral<br>Drug: Mycophenolate<br>* Pharmaceutical Form: Tablet Route of Administration: Oral<br>|
| Experimental: BIVV020 with Standard of Care (SOC) Cohort B<br>Eligible participants will receive BIVV020 and SOC which includes plasmapheresis, IVIg, corticosteroids, rituximab. | Drug: BIVV020 (SAR445088)<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Intravenous immunoglobulin (IVIg)<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Rituximab or biosimilar<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Corticosteroids<br>* Pharmaceutical Form: Vary Route of Administration: Vary<br>|
| Other: Standard of Care (SOC) Cohort B<br>SOC includes plasmapheresis, IVIg, corticosteroids, rituximab. | Drug: Intravenous immunoglobulin (IVIg)<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Rituximab or biosimilar<br>* Pharmaceutical Form: Solution for injection Route of Administration: Intravenous<br>Drug: Corticosteroids<br>* Pharmaceutical Form: Vary Route of Administration: Vary<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Treatment failure rate | Defined as the proportion of participants meeting at least one of the following criteria: Biopsy-proven active AMR as per Banff Criteria 2019 as per central pathology assessment, Graft loss. | Up to Week 49 | 
| Cohort B: AMR resolution rate | Defined as the proportion of participants with post-treatment biopsy not fulfilling active AMR diagnosis criteria as per Banff Criteria 2019 as per central pathology assessment. | Up to Week 49 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort A: Treatment failure rate per local assessment using Banff criteria 2019 |  | Up to Week 49 | 
| Cohort B: AMR resolution rate per local assessment using Banff criteria 2019 |  | Up to Week 49 | 
| Change in renal function from baseline per central laboratory assessment of estimated glomerular filtration rate (eGFR) from serum creatinine using Modification of Diet in Renal Disease equation (MDRD) |  | Up to 22 weeks after end of treatment period | 
| Change in renal function from baseline per central laboratory assessment using protein: creatinine ratio |  | Up to 22 weeks after end of treatment period | 
| Change in allograft histopathology Banff score |  | Up to Week 49 | 
| Graft survival as predicted by iBOX |  | Up to Week 49 | 
| Assessment of adverse events (AEs) | Number of participants with treatment emergent adverse events (TEAEs)/ serious adverse events (SAES), laboratory abnormalities | Up to end of study, up to approximately 2 years | 
| Change in systemic lupus erythematosus (SLE) panel |  | Up to 22 weeks after end of treatment period | 
| Plasma exposure of BIVV020 assessing pharmacokinetic parameter Cmin | Cmin is defined as the minimum concentration after injection | Up to 22 weeks after end of treatment period | 
| Plasma exposure of BIVV020 assessing pharmacokinetic parameter AUC | AUC is defined as the area under plasma concentration versus time curve | Up to 22 weeks after end of treatment period | 
| Number of participants with anti-BIVV020 antibodies | Number of participants developed drug-induced ADAs | Up to 22 weeks after end of treatment period |