Dr. Christof Geisen (Frankfurt a. M./ DE), Erika Fleck (Frankfurt a. M./ DE), Stephan Martin Gastón Schäfer (Frankfurt a. M./ DE), Carmen Walter (Frankfurt a. M./ DE), Susanne Bräuninger (Frankfurt a. M./ DE), Jens Søndergaard Jensen (Herlev/ DK), Róisín Armstrong (New Haven, CT/ US), Doug Sheridan (New Haven, CT/ US), Kiran Patki (New Haven, CT/ US), Mette Kjaer (Hammerfest/ NO), Frank Behrens (Frankfurt a. M./ DE), Prof. Erhard Seifried (Frankfurt a. M./ DE), Jens Kjeldsen-Kragh (Tromsø/ NO; Lund/ SE), Michaela Köhm (Frankfurt a. M./ DE)
Background
Fetal and neonatal alloimmune thrombocytopenia (FNAIT), based on a rare development of maternal alloantibodies against fetal platelets, may result in potentially catastrophic bleeding. No preventative FNAIT treatments are currently available. Prophylactic treatment with a monoclonal human platelet antigen (HPA)-1a antibody (RLYB212) is intended to drive rapid phagocytosis of fetal-derived HPA-1a antigen in maternal circulation to prevent alloimmunization to HPA-1a.
Methods
Following approval by the University Hospital Ethics Committee, participant informed consent was obtained. We assessed the dose-effect relationship of subcutaneous monoclonal anti-HPA-1a antibody (RLYB212) to eliminate HPA-1ab platelets transfused to HPA-1bb participants. Participants (HPA-1bb/human leukocyte antigen [HLA]-A2–negative healthy males) received a single dose of RLYB212 (0.09 mg or 0.29 mg) or placebo on day 1, followed by transfusion with 10 X109 HPA-1ab/HLA-A2–positive platelets on day 8. The proportion of HPA-1ab platelets in circulation over 7 days was determined by flow cytometry using HLA-A2 antibodies.
Results
RLYB212 rapidly eliminated HPA-1ab platelets, with a mean reduction in platelet elimination half-life of ≥90%, thus meeting proof-of-concept criteria. Platelet elimination kinetics of RLYB212 were dose-dependent and biphasic, with a mean lag phase of 4.8 h (0.09 mg) and 2.0 h (0.29 mg) vs 15.0 h for placebo; mean terminal half-life was 5.8 h (0.09 mg) and 1.6 h (0.29 mg) for RLYB212 vs 71.7 h for placebo.
Conclusion
Subcutaneous RLYB212 treatment resulted in dose-dependent and rapid elimination of HPA-1ab platelets in HPA-1bb participants. Platelet elimination kinetics were consistent with those of RhD(+) erythrocytes transfused to RhD-negative individuals after intramuscular administration of anti-RhD, which is known to prevent RhD alloimmunization when administered within 72 h of a suspected fetal-maternal hemorrhage. Our data support the potential use of subcutaneous RLYB212 as a prophylactic for FNAIT.
Offenlegung Interessenkonflikt:
Study-Funding: Rallybio, IPA, LLC
Invited talks abstract/summary