Z Geburtshilfe Neonatol 2013; 217 - V25_5
DOI: 10.1055/s-0033-1361353

Prophylactic treatment to prevent immunisation against human platelet antigen (HPA) 1a – a new approach for prevention of foetal and neonatal alloimmune thrombocytopenia

K Järås 1, on behalf of the PROFNAIT consortium (www.profnait.eu)
  • 1PROFNAIT consortium, Tromsø, Norway

Aim: The aim of this project is to examine if hyperimmune anti-HPA-1a IgG can prevent post delivery immunisation against the HPA-1a epitope. Our prophylactic treatment will prevent foetal and neonatal alloimmune thrombocytopenia (FNAIT) in the foetus/newborn in subsequent pregnancies in the same way as the hyperimmune anti-D IgG prevents haemolytic disease of the foetus and newborn (HDFN).

Methodology: The theory behind this prophylactic treatment is based on research that shows a closer similarity between FNAIT and HDFN than previously believed. A preclinical proof-of-concept study in mice has shown that administration of anti-β3 integrin induces antibody-mediated immune suppression (AMIS) and prevents poor pregnancy outcome in FNAIT. The development of the current medicinal product includes internationally joint forces for plasma collection from women who previously have had a pregnancy complicated with FNAIT, manufacturing of the clinical trial material, phase I/II and III clinical trials and dissemination of results.

Results: The PROFNAIT consortium was formed and granted 6 million € from the European Union's 7th Framework Programme. The European Medicines Agency's Committee for Orphan Medicinal Products and the Food and Drug Administration in the USA have granted Hyperimmune anti-HPA-1a IgG Orphan Medicinal Product Designation. A Phase I/II protocol has been developed, where optimal clearance of HPA 1ab platelets in HPA 1bb volunteers will be investigated to determine the dose to be used in the phase III clinical trials. To gain high enough statistical power 85,000 pregnant women will have their HPA-1a type determined. Among these women we will identify 1,600 HPA-1a negative individuals at risk of being HPA-1a-immunised.

Conclusion: The PROFNAIT consortium has taken the first steps towards the development of a polyclonal antibody-based prophylaxis preventing FNAIT, and started the preparations for phase I/II and phase III clinical trials.