Recombinant anti-D for prevention of maternal-foetal Rh(D) alloimmunization: a randomized multi-centre clinical trial

Abstract

Objective: To compare the efficacy and safety of recombinant anti-D (R-anti-D) with conventional polyclonal anti-D (Poly anti-D) in preventing maternal-fetal rhesus D (RhD) alloimmunization and to investigate the immunogenicity of R-anti-D.

Methods: This was a randomized, open-label, multi-center clinical trial conducted in RhD-negative pregnant women who did not receive antenatal anti-D who delivered RhD-positive babies and showed negative indirect Coombs tests (ICTs) at baseline. The women were randomized in a 2:1 ratio to R-anti-D or Poly anti-D groups and were administered 300 mcg (IM) of the corresponding drug within 72 hours of delivery. ICT was performed 72 hours, 90 days, and 180 days after anti-D injection. Serum samples were collected to check for the development of antibodies against R-anti-D at days 90 and 180, using bridging enzyme-linked immunosorbent assay. The proportion of subjects who had positive ICT results at days 90 and 180 were compared between the groups using Fisher's exact test.

Results: A total of 144 women were randomized to the R-anti-D group and 71 to the Poly anti-D group. Three women in the R-anti-D and none in the Poly anti-D group had a positive ICT result at day 90. No woman in either group had positive ICT result at day 180. Both drugs were well tolerated with only 4 reports of adverse events in each group-all were mild, non-serious, and resolved without sequelae. No subject developed antibodies against R-anti-D.

Conclusion: The studied R-anti-D is comparable in efficacy to conventional Poly anti-D and is safe and non-immunogenic.Trial Registration: Clinical Trials Registry of India Identifier: Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/03/008101.

Keywords: Newborn hemolytic disease; Recombinant proteins; Rh isoimmunization; Rho(D) immune globulin.

Fig. 1. Manufacturing process and link between monoclonal anti-D (Rhoclone^®) and recombinant anti-D.

Fig. 2. Principle of biotin-digoxigenin complex-based bridging ELISA to test the immunogenicity of R-anti-D.

ADA, antidrug antibody; R-anti-D, recombinant anti-D; HRP, horseradish peroxidase; TMB, tetramethylbenzidine; ELISA, enzyme-linked immunosorbent assay.

Fig. 3. Trial and participant flow. One subject from the R-anti-D group and 4 subjects from the Poly anti-D group were excluded from efficacy analysis owing to major protocol deviations.

R-anti-D, recombinant anti-D; Poly anti-D, polyclonal anti-D; F/U, followed-up.