Clinical Trials of Therapeutics for the Prevention of Congenital Zika Virus Disease: Challenges and Potential Solutions.
Zika virus (ZIKV) infection in pregnancy is associated with adverse fetal outcomes, such as microcephaly and other congenital malformations. No therapeutic options are available to pregnant women with ZIKV infection to prevent these effects. Drug trials in pregnancy raise several scientific, ethical, and logistic challenges, which are compounded further in ZIKV because of limited knowledge of the disease pathophysiology and a product development pipeline in its infancy. We evaluate the major challenges in choosing therapeutics to prevent congenital ZIKV disease and conducting clinical trials of these treatments, with a focus on preventing congenital central nervous system malformations. These challenges must be characterized and planned for now so that clinical trials can progress expediently and effectively in the future.
From University of Oxford, Oxford, United Kingdom.
Alex P
AP
Salam
From University of Oxford, Oxford, United Kingdom.
Amanda
A
Rojek
From University of Oxford, Oxford, United Kingdom.
Jake
J
Dunning
From University of Oxford, Oxford, United Kingdom.
Peter W
PW
Horby
D000906:Antibodies / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008831:Microcephaly / Q000517:prevention & control / Q000821:virology; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects; D013723:Teratogens; D014779:Virus Replication / Q000187:drug effects; D000071243:Zika Virus Infection / Q000150:complications / Q000151:congenital* / Q000517:prevention & control*; D000094963:Axl Receptor Tyrosine Kinase
D000906:Antibodies; D000998:Antiviral Agents; D011518:Proto-Oncogene Proteins; D013723:Teratogens; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human