Transplant Rejection
Conditions
Brief summary
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
Up to approximately 2 years
Interventions
DRUGBIVV020 (SAR445088)
Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
DRUGTacrolimus
Pharmaceutical Form: Tablet Route of Administration: Oral
DRUGMycophenolate
Pharmaceutical Form: Tablet Route of Administration: Oral
DRUGCorticosteroids
Pharmaceutical Form: Vary Route of Administration: Vary
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Randomization for Cohort B only
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Positive HIV. 2. Positive HBV. 3. HCV with detectable HCV RNA. 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A: Treatment failure rate | Up to Week 49 | 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. |
| Cohort B: AMR resolution rate | Up to Week 49 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to end of study, up to approximately 2 years | Number of participants with treatment emergent adverse events (TEAEs)/ serious adverse events (SAES), laboratory abnormalities |
| Change in systemic lupus erythematosus (SLE) panel | Up to 22 weeks after end of treatment period | — |
| Plasma exposure of BIVV020 assessing pharmacokinetic parameter Cmin | Up to 22 weeks after end of treatment period | Cmin is defined as the minimum concentration after injection |
| Plasma exposure of BIVV020 assessing pharmacokinetic parameter AUC | Up to 22 weeks after end of treatment period | AUC is defined as the area under plasma concentration versus time curve |
| Number of participants with anti-BIVV020 antibodies | Up to 22 weeks after end of treatment period | Number of participants developed drug-induced ADAs |
Countries
Canada, France, Germany, Italy, Spain, Sweden, United States
Outcome results
None listed