Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant candidates (COLT)

Principal Investigators: Abhijit (Ajit) P Limaye, MD and Cynthia Fisher, MD MPH

Study Design: Phase II, randomized, double-blind, placebo-controlled, multi-center clinical trial

Sponsor: The National Institute of Allergy and Infectious Diseases (NIAID)

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in transplant recipients and other immunosuppressed populations. In this NIH-sponsored study, we will assess the safety, immunogenicity, and efficacy of a promising CMV vaccine (“Triplex”) in adult liver transplant candidates at high risk for developing CMV complications after transplant.

Study Design

This is a phase II, randomized, double-blind, placebo-controlled, multi-center clinical trial in CMV seronegative prospective liver transplant recipients to determine the efficacy of two doses of CMV-MVA Triplex vaccine, prior to liver transplant.

The study will enroll approximately 416 CMV seronegative liver transplant candidates at 17 different sites across the United States. Study participants will be randomized 1:1 to receive either two doses of the CMV Triplex vaccine or matching placebo pre-transplant, given one month apart. Participants will be followed for up to 1 year pre-transplant after vaccination. In those who receive a liver transplant within that year, they will be followed for 6 months after transplant for safety and immunogenicity.

Our ultimate target population is 110 participants who receive a liver transplant within one year of enrollment from a donor who is CMV seropositive, called CMV donor (D) positive, Recipient (R) negative, or CMV D+R-. CMV D+R- patients comprise ~25% of the solid organ transplant population, but account for >80% of CMV disease, and is the population with greatest unmet need for novel interventions. CMV D+R- participants will be followed for 6 months post-transplant for vaccine efficacy in addition to safety and immunogenicity. They will undergo Pre-Emptive Therapy as their CMV prevention strategy, consisting of weekly CMV PCR testing for the first 100 days following transplant with initiation of antiviral therapy with any detection of CMV in the blood.

Primary Outcome Measure

To assess the effect of pre-transplant Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days post-transplant in CMV D+R- liver transplant recipients.

Secondary Outcome Measures

1.       To evaluate the effect of pre-Tx Triplex vaccination on rates of CMV disease in the first 6 months after transplant in CMV D+R- liver transplant recipients

2.       To evaluate the difference in mean days of CMV AVT in the two arms and its 95% confidence interval (among all D+R- LTxRs).

Study Sites

  • University of Maryland

  • University of Miami

  • University of Michigan

  • University of Nebraska

  • University of Pennsylvania

  • University of Pittsburgh

  • University of Texas Southwestern

  • Vanderbilt University

  • University of Washington (Main Site)

  • Duke University

  • Emory University

  • Johns Hopkins University

  • Mayo Clinic- Rochester

  • Northwestern University

  • Oregon Health Sciences University

  • Stanford University

  • University of California San Francisco