Clinical trial NCT05156710: BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR)
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Transplant Rejection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-12-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Cohort A: Treatment failure rate
timeFrame: Up to Week 49
measure: Cohort B: AMR resolution rate
timeFrame: Up to Week 49
Secondary outcomes:
measure: Cohort A: Treatment failure rate per local assessment using Banff criteria 2019
timeFrame: Up to Week 49
measure: Cohort B: AMR resolution rate per local assessment using Banff criteria 2019
timeFrame: Up to Week 49
measure: 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)
timeFrame: Up to 22 weeks after end of treatment period
measure: Change in renal function from baseline per central laboratory assessment using protein: creatinine ratio
timeFrame: Up to 22 weeks after end of treatment period
measure: Change in allograft histopathology Banff score
timeFrame: Up to Week 49
measure: Graft survival as predicted by iBOX
timeFrame: Up to Week 49
measure: Assessment of adverse events (AEs)
timeFrame: Up to end of study, up to approximately 2 years
measure: Change in systemic lupus erythematosus (SLE) panel
timeFrame: Up to 22 weeks after end of treatment period
measure: Plasma exposure of BIVV020 assessing pharmacokinetic parameter Cmin
timeFrame: Up to 22 weeks after end of treatment period
measure: Plasma exposure of BIVV020 assessing pharmacokinetic parameter AUC
timeFrame: Up to 22 weeks after end of treatment period
measure: Number of participants with anti-BIVV020 antibodies
timeFrame: Up to 22 weeks after end of treatment period
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center- Site Number : 8400100
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles Medical Center- Site Number : 8400103
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Parnassus Heights- Site Number : 8400001
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital- Site Number : 8400007
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital- Site Number : 8400004
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Medical Center- Site Number : 8400102
state: New York
city: Madison
country: United States
facility: University of Wisconsin Hospitals and Clinics- Site Number : 8400003
state: Wisconsin
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240101
state: British Columbia
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240001
state: British Columbia
city: London
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Bordeaux
country: France
facility: Investigational Site Number : 2500007
city: Créteil
country: France
facility: Investigational Site Number : 2500002
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Toulouse
country: France
facility: Investigational Site Number : 2500005
city: Berlin
country: Germany
facility: Investigational Site Number : 2760002
city: Essen
country: Germany
facility: Investigational Site Number : 2760004
city: Munich
country: Germany
facility: Investigational Site Number : 2760001
city: Bologna
country: Italy
facility: Investigational Site Number : 3800004
state: Emilia-Romagna
city: Rome
country: Italy
facility: Investigational Site Number : 3800002
state: Lazio
city: Brescia
country: Italy
facility: Investigational Site Number : 3800001
state: Lombardia
city: Milan
country: Italy
facility: Investigational Site Number : 3800003
state: Milano
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240002
state: Madrid, Comunidad De
city: Huddinge
country: Sweden
facility: Investigational Site Number : 7520001
city: Uppsala
country: Sweden
facility: Investigational Site Number : 7520002
Study officials:
References:
citation: 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.