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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05156710

Collaborator

(none)

Enrollment

Locations

Arms

35.5

Anticipated Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Transplant Rejection	Drug: BIVV020 Drug: Intravenous immunoglobulin (IVIg) Drug: Rituximab Drug: Antithymocyte globulin (ATG) Drug: Tacrolimus Drug: Mycophenolate Drug: Corticosteroids	Phase 2

Detailed Description

Up to approximately 2 years

Study Design

Study Type:

Interventional

Anticipated Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jun 9, 2022

Anticipated Primary Completion Date :

Nov 14, 2024

Anticipated Study Completion Date :

May 26, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 to whom they are sensitized, and/or required desensitization prior to transplantation.

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).
18-75 years old at the time of consent.

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 infection requiring antibiotic treatment against an identified or suspected bacterial pathogen.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :0360003	Westmead	New South Wales	Australia	2145
2	Investigational Site Number :1240001	Vancouver	British Columbia	Canada	V6Z 1Y6
3	Investigational Site Number :1240003	Montreal	Quebec	Canada	H4A 3J1
4	Investigational Site Number :2500007	Bordeaux		France	33000
5	Investigational Site Number :2500002	Creteil		France	94000
6	Investigational Site Number :2500001	Paris		France	75010
7	Investigational Site Number :2500004	Suresnes		France	92150
8	Investigational Site Number :2500005	Toulouse		France	31059
9	Investigational Site Number :3800001	Brescia	Lombardia	Italy	25123
10	Investigational Site Number :7240004	Barcelona	Barcelona [Barcelona]	Spain	08035
11	Investigational Site Number :7240001	Madrid / Madrid	Madrid, Comunidad De	Spain	28007
12	Investigational Site Number :7240003	Madrid	Madrid, Comunidad De	Spain	28041
13	Investigational Site Number :7240002	Madrid	Madrid, Comunidad De	Spain	28046
14	Investigational Site Number :7520001	Huddinge		Sweden
15	Investigational Site Number :7520002	Uppsala		Sweden	751 85