HB-101 is a bivalent recombinant vaccine against human CMV infection. This is a randomized, placebo-controlled, phase 2 study to assess the safety, reactogenicity, immunogenicity, and efficacy of HB-101 in CMV-Seronegative patients receiving a kidney transplant from a CMV-Seropositive living donor and CMV-Seropositive patients.Patients enrolled should have a living donor kidney transplantation ideally planned between two to four months after the first injection of study drug (HB-101 or placebo).
This is a randomized, placebo-controlled, phase 2 study to assess the safety, reactogenicity, immunogenicity, and efficacy of HB-101 in adult patients awaiting kidney transplantation. For Groups 1 and 2, adult CMV-seronegative (-) patients awaiting kidney transplant from a CMV-seropositive (+) living donor will be enrolled according to treatment intent with regard to the method of CMV prevention after transplant (either preemptive or prophylactic). This will be defined at study enrollment by the investigator and institutional standards. Patients enrolled in Group 1 and 2 will be randomized to receive HB-101 or placebo. For Group 3, adult CMV-seropositive (+) patients awaiting kidney transplant from either CMV-seropositive(+) or CMV-seronegative(-) living donors will be enrolled. Group 3 will be open label where all patients will receive HB-101. The post transplant management for Group 3 patients will also follow either preemptive or prophylactic method per the institution standards. The intent of the study is to administer three doses of the study drug (HB-101 or placebo) prior to transplantation and within proximity to the time of transplantation. However, two doses of study drug will be sufficient for the patients to be included in the efficacy analyses if a third dose of study drug is not feasible due to transplantation timelines. Patients will not receive study drug after transplantation. Patients will be recruited globally from transplant centers. The total duration of the study of each patient participating in the study will be approximately 15 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
HB-101 is a bivalent vaccine that contains two replication deficient recombinant lymphocytic choriomeningitis virus (rLCMV) vectors expressing pp65 and a truncated isoform of gB of human CMV.
Saline will be used for placebo.
The 1917 Clinic at UAB
Birmingham, Alabama, United States
Number of Participants With Adverse Events and Serious Adverse Events
Assess the number and severity of participants with adverse events and serious adverse events
Time frame: 15 Months
Assessment of Humoral Immunogenicity Analyses
Assessment of CMV neutralizing antibody titers (NTAs) at day of Transplant defined by log10 virus neutralising unit(s)
Time frame: 15 Months
Number of Patients With Injection Site Events.
Number of patients experiencing a local or generalized injection site reaction
Time frame: 15 Months
Change of Oral Body Temperature.
Oral body temperature was measured in degrees Celsius prior to study drug administrations and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
Time frame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
Change of Respiration Rate.
Respiration rate in breaths per minute was measured prior to study drug administration and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
Time frame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months.
Change of Blood Pressure.
Diastolic and Systolic Blood Pressure was measured in millimeters of mercury (mmHg) prior to study drug administration and seven days after. The results express the change from baseline (defined as the last measurement prior to the first dose of study drug) to Dose 3.
Time frame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
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TRIPLE
Enrollment
83
California Institute of Renal Research
La Mesa, California, United States
UC Davis Health Systems
Sacramento, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
Indiana University/IU Health
Indianapolis, Indiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
The Christ Hospital
Cincinnati, Ohio, United States
University of Cincinnati (UC) - College of Medicine
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Oklahoma University
Oklahoma City, Oklahoma, United States
...and 15 more locations
Assessment of Cellular Immunogenicity Analyses
Assessment of positive CMV IFNγ ELISPOT results for pp65 and gB defined by Spot forming cells / mio PBMC per CMV Management Strategy and Doses Before Transplant
Time frame: 15 months
Time to Clinically Significant CMV Infection.
Measure the time to clinically significant CMV infection, CMV disease, and CMV syndrome. Time to infection was defined as the number of days of the first quantifiable result above the LLOQ monitored for 12 months after transplantation.
Time frame: 12 months
Number of Participants With CMV Viremia Requiring Anti Viral Therapy
Measure the number of patients with CMV viremia requiring anti viral therapy for CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and to be treated prophylactically for CMV post transplant.
Time frame: 12 months
The Time to CMV Viremia Requiring Anti Viral Therapy.
Measure the time to CMV viremia requiring anti viral therapy for CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and to be treated prophylactically for CMV post transplant.
Time frame: 12 months
Number of Participants Requiring Anti-CMV Therapy
Measure the number of participants requiring anti-CMV therapy (at therapeutic doses) in CMV seropositive (+) recipients awaiting kidney transplant.
Time frame: 12 months
The Duration of Anti-CMV Therapy Courses Required.
Measure duration (in days) of anti-CMV therapy courses (at therapeutic doses) required in CMV seropositive (+) recipients awaiting kidney transplant.
Time frame: 12 months
Number of Participants With Organ Rejection
Assessment of number of participants with graft failure leading to biopsy-confirmation rejection of organ post transplantation.
Time frame: Up to 12 months post transplantation
Time to Organ Rejection
Measurement of time (in days) between transplantation and graft failure leading to biopsy-confirmation rejection of organ
Time frame: Up to 12 months post transplantation