Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients.
Ishida JH, Patel A, et al.Antimicrobial Agents and Chemotherapy 2016 [record in progress]
Aims
To examine the safety and activity of RG7667 in the prevention of Cytomegalovirus (CMV) infection in high-risk kidney transplant recipients.
Interventions
Participants were randomized to receive a total of four intravenous doses of RG7667 (at the time of transplant, and 1, 4, and 8 weeks post-transplant) versus placebo.
Participants
120 CMV-seronegative patients, aged ≥ 18 years, receiving a first or second kidney transplant from a CMV-seropositive living or deceased donor.
Outcomes
The primary outcome measured was the proportion of patients with CMV viremia within 12 weeks posttransplant. Secondary measured outcomes included the proportion of patients with CMV viremia within 24 weeks posttransplant, the proportion of patients with CMV disease within 24 weeks posttransplant, time to CMV viremia, viral load at first detection of CMV viremia, peak CMV viral load, and initiation of antiviral therapy within 12 and 24 weeks posttransplant. Adverse events (AEs), treatment-emergent AEs and pharmokinetic and immunogenicity assessments were also measured.
Follow-up
24 weeks
CET Conclusions
This small phase 2 study investigated the antiviral effect of a novel combination monoclonal antibody to CMV in high risk (CMV +/-) kidney transplant recipients. Patients were randomised to RG7667 or placebo, with pre-emptive antiviral treatment at the discretion of local investigators in each group. No additional antiviral prophylaxis was given. Rates of CMV viremia were high in both groups, but perhaps unsurprisingly were lower in the RG7667 group at 24 weeks post-transplant. More encouragingly, rates of CMV disease (syndrome or tissue invasive disease) and the use of additional antiviral therapy were both lower in the RG7667 arm. Side effects did not differ significantly between groups, which makes RG7667 a potentially useful alternative to the relatively toxic antiviral agents in current use. A larger trial comparing RG7667 to standard valganciclovir prophylaxis would be interesting to see.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01753167