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

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.

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

Study Overview

• Status: Recruiting
• Conditions: Transplant Rejection
• Intervention / Treatment: Drug: Antithymocyte globulin (ATG); Drug: Tacrolimus; Drug: Mycophenolate; Drug: Intravenous immunoglobulin (IVIg); Drug: Corticosteroids; Drug: BIVV020 (SAR445088); Drug: Rituximab or biosimilar

Detailed Description

Up to approximately 2 years

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Investigational Site Number : 1240101
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Recruiting
      • Investigational Site Number : 1240001
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Investigational Site Number : 1240003
• France
  • Bordeaux, France, 33000
    • Recruiting
    • Investigational Site Number : 2500007
  • Creteil, France, 94000
    • Recruiting
    • Investigational Site Number : 2500002
  • Paris, France, 75010
    • Recruiting
    • Investigational Site Number : 2500001
  • Suresnes, France, 92150
    • Recruiting
    • Investigational Site Number : 2500004
  • Toulouse, France, 31059
    • Recruiting
    • Investigational Site Number : 2500005
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Investigational Site Number : 2760002
  • Essen, Germany, 45122
    • Recruiting
    • Investigational Site Number : 2760004
  • München, Germany, 81675
    • Recruiting
    • Investigational Site Number : 2760001
• Italy
  • Milano, Italy, 20126
    • Recruiting
    • Investigational Site Number : 3800003
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • Investigational Site Number : 3800004
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Investigational Site Number : 3800002
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • Recruiting
      • Investigational Site Number : 3800001
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Recruiting
      • Investigational Site Number : 7240004
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28041
      • Recruiting
      • Investigational Site Number : 7240003
    • Madrid, Madrid, Comunidad De, Spain, 28046
      • Recruiting
      • Investigational Site Number : 7240002
    • Madrid / Madrid, Madrid, Comunidad De, Spain, 28007
      • Recruiting
      • Investigational Site Number : 7240001
• Sweden
  • Huddinge, Sweden
    • Recruiting
    • Investigational Site Number : 7520001
  • Uppsala, Sweden, 751 85
    • Recruiting
    • Investigational Site Number : 7520002
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles (UCLA) - Ronald Reagan UCLA Medical Center Site Number : 8400103
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center Site Number : 8400100
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco Site Number : 8400001
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital Site Number : 8400007
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Brigham & Women's Hospital Site Number : 8400004
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center Site Number : 8400102
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University Of Wisconsin Hospital And Clinics Site Number : 8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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: 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; Drug: BIVV020 (SAR445088); Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
Experimental: BIVV020 with Standard of Care (SOC) Cohort B; Eligible participants will receive BIVV020 and SOC which includes plasmapheresis, IVIg, corticosteroids, rituximab.	Drug: Intravenous immunoglobulin (IVIg); Pharmaceutical Form: Solution for injection Route of Administration: Intravenous; Drug: Corticosteroids; Pharmaceutical Form: Vary Route of Administration: Vary; Drug: BIVV020 (SAR445088); Pharmaceutical Form: Solution for injection Route of Administration: Intravenous; Drug: Rituximab or biosimilar; Pharmaceutical Form: Solution for injection Route of Administration: Intravenous
Other: Standard of Care (SOC) Cohort B; SOC includes plasmapheresis, IVIg, corticosteroids, rituximab.	Drug: Intravenous immunoglobulin (IVIg); Pharmaceutical Form: Solution for injection Route of Administration: Intravenous; Drug: Corticosteroids; Pharmaceutical Form: Vary Route of Administration: Vary; Drug: Rituximab or biosimilar; Pharmaceutical Form: Solution for injection Route of Administration: Intravenous

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Karpman D, Bekassy Z, Grunenwald A, Roumenina LT. A role for complement blockade in kidney transplantation. Cell Mol Immunol. 2022 Jul;19(7):755-757. doi: 10.1038/s41423-022-00854-5. Epub 2022 Mar 24. No abstract available.

Helpful Links

• ACT17012 kidney transplant - antibody-mediated rejection website

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Estimated): November 14, 2024
• Study Completion (Estimated): December 3, 2026

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Calcineurin Inhibitors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Rituximab; Tacrolimus; gamma-Globulins; Rho(D) Immune Globulin; Antilymphocyte Serum
• Other Study ID Numbers: ACT17012; U1111-1267-2612 (Registry Identifier: ICTRP); 2021-000010-41 (EudraCT Number); 2023-509936-25-00 (Registry Identifier: CTIS); 2023-509936-25 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No