Anti-C1s monoclonal antibody BIVV009 in late antibody-mediated kidney allograft rejection-results from a first-in-patient phase 1 trial

Am J Transplant. 2018 Apr;18(4):916-926. doi: 10.1111/ajt.14528. Epub 2017 Oct 31.


The classical pathway (CP) of complement may contribute to the pathogenesis of antibody-mediated rejection (ABMR). Selective CP blockade may be a promising strategy to counteract rejection. The objective of this first-in-patient phase 1b trial was to evaluate the safety/tolerability and CP-blocking potential of 4 weekly doses (60 mg/kg) of the anti-C1s antibody BIVV009 in complement-mediated disorders. Here we describe the results in a cohort of 10 stable kidney transplant recipients (median of 4.3 years posttransplantation) with late active ABMR and features of CP activation, such as capillary C4d or complement-fixing donor-specific antibodies (DSA). During 7 weeks follow-up, no severe adverse events were reported, and BIVV009 profoundly inhibited overall and DSA-triggered CP activation in serum. Five of 8 C4d-positive recipients turned C4d-negative in 5-week follow-up biopsies, while another 2 recipients showed a substantial decrease in C4d scores. There was, however, no change in microcirculation inflammation, gene expression patterns, DSA levels, or kidney function. In conclusion, we demonstrate that BIVV009 effectively blocks alloantibody-triggered CP activation, even though short-course treatment had no effect on indices of activity in late ABMR. This initial trial provides a valuable basis for future studies designed to clarify the therapeutic value of CP blockade in transplantation. NCT#02502903.

Trial registration: NCT02502903.

Keywords: clinical research/practice; clinical trial; complement biology; immunosuppressant - fusion proteins and monoclonal antibodies; immunosuppression/immune modulation; kidney transplantation/nephrology; pathology/histopathology; protocol biopsy; rejection: antibody-mediated (ABMR).

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Antibodies, Monoclonal / therapeutic use*
  • Complement Activation / immunology
  • Complement C1s / immunology*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Survival / drug effects*
  • Graft Survival / immunology
  • HLA Antigens / immunology
  • Humans
  • Isoantibodies / adverse effects*
  • Kidney Failure, Chronic / surgery*
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Tissue Donors


  • Antibodies, Monoclonal
  • HLA Antigens
  • Isoantibodies
  • Complement C1s

Associated data