Plasminogen replacement therapy for the treatment of children and adults with congenital plasminogen deficiency
Congenital plasminogen deficiency is an exceedingly rare autosomal recessive disorder characterized by pseudomembranous lesions on mucous membranes throughout the body, abnormal wound healing and infertility. With the highest severity in infants and children, it is caused by mutations in PLG and is estimated to affect 1.6 individuals per million. Treatment is usually surgical excision of the lesions, although plasminogen concentrates purified from human plasma are being developed as an IV replacement therapy.
This is an open label study of human plasminogen given every 2-4 days based on pharmacokinetic (PK) studies, to achieve a trough plasminogen level of 10% above the patient's baseline. The primary outcome was the ability to obtain this PK endpoint; secondary outcomes were overall clinical success in both the number and size of lesions or change in organ function. Clinical examination of visible lesions and medical imaging of non-visible lesions were used to quantify change.
14 patients, including 5 children, were enrolled. All achieved the primary endpoint, with three patients having transient falls in their trough levels associated with interruption of the infusion schedule. PK studies reveal an approximate 2-week interval to achieve steady state levels. Clinical endpoints also had a 100% success rate, with resolution or improvement of all visible and non-visible manifestations assessed at baseline. The therapy was well tolerated in all patients.
Because of the very small sample size, there were no power calculations or statistical determinations, which the authors acknowledged a priori.