Vical Incorporated has announced the enrolment of the 20th haematopoietic stem cell transplant recipient in the company's phase II trial of a DNA vaccine against cytomegalovirus (CMV). After the 20th recipient's two-month follow-up visit, an independent data safety monitoring board will conduct an interim evaluation of safety data for all subjects enrolled in the trial.
"We are pleased that recent protocol amendments have accelerated patient enrolment in our CMV vaccine trial," said Ronald B Moss, MD, vice president of clinical development at Vical, "and we hope to sustain the momentum by continuing to enroll additional patients as safety data are being collected and evaluated. Our novel immunotherapeutic vaccine may address the serious healthcare problem of CMV reactivation for transplant patients, and could eventually be useful in preventing birth defects caused by CMV infection of pregnant women."
The double-blind, placebo-controlled phase II trial was designed to compare safety of the vaccine against placebo in approximately 80 matched, related donor/recipient pairs scheduled for haematopoietic stem cell transplants. Subsequent protocol amendments intended to provide additional scientific insights and speed up trial enrolment include a more convenient donor vaccination schedule and vaccination of recipients only. Because most recipients are expected to face a natural viral challenge as pre-existing CMV infection reactivates under immunosuppression, the primary efficacy endpoint is the occurrence rate of clinically significant CMV levels in patients receiving vaccine compared with patients receiving placebo. Other important endpoints include immune responses against the specific CMV features targeted by the vaccine.
CMV is a herpes virus that infects more than half of all adults in the United States by age 40, and is even more widespread in developing countries. While a healthy immune system typically protects an infected person against CMV disease, it rarely succeeds in completely eliminating the infection, and those whose immune systems are not fully functional are at high risk of CMV proliferation, potentially leading to severe illness or death. These include transplant patients who take immunosuppressive drugs, and fetuses and newborns of mothers who first become infected during pregnancy.
CMV infection affects 30 to 60 per cent of the patients undergoing various transplant procedures, causing transplant rejection, serious illness and even death if untreated. Expensive antiviral drug therapy is used to control the disease, but does not eliminate the infection. Congenital CMV infection affects one out of every hundred infants, and causes severe consequences in about 3,600 infants and death in about 400 each year in the United States.
There is no approved vaccine against CMV. Vaccine approaches that result in predominantly antibody responses to CMV have not proven highly effective in transplant patients. Vaccine approaches using live, attenuated viruses can induce both antibody and cellular immune responses, but pose a potential safety concern, particularly for immunocompromised patients, of causing the disease they are intended to prevent. Vical's novel DNA vaccine approach is designed to induce both antibody and cellular immune responses against specific features of the CMV virus without the risk of causing CMV disease.