A Study of CMV Vaccine (HB-101) in Kidney Transplant Patients
- Conditions
- Kidney TransplantationCytomegalovirus (CMV) Infection
- Interventions
- Biological: placeboBiological: HB-101 vaccine
- Registration Number
- NCT03629080
- Lead Sponsor
- Hookipa Biotech GmbH
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
Patients who meet all of the following key inclusion criteria will be eligible to participate in the study:
- Male or female patients 18 years of age or older.
- Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards.
- For Groups 1 and 2 only: Patients must be CMV immunoglobulin G (IgG) seronegative (-) and receiving kidney for transplantation from donors who are CMV IgG seropositive (+).
- For Group 3 only: Patients must be CMV immunoglobulin G (IgG) seropositive (+) and receiving kidney for transplantation from donors who are either CMV IgG seronegative (-) or seropositive (+).
- Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator.
Patients who meet any of the following key criteria will be excluded from the study:
- Patients planning to undergo multi-organ transplantation.
- Patients participating in another interventional clinical study.
- Previous vaccination with an investigational CMV vaccine.
- Any confirmed or suspected immunodeficiency disorder (based on medical history and physical examination) that could interfere with the immune response or that presents a risk for the patient to receive a vaccine candidate in development.
- Treatment with any chronic immunosuppressive medication or other immuno modifying drugs within 6 months prior to study entry. However, inhaled and topical steroids and low-dose oral corticosteroids (<10 milligrams a day of prednisone or equivalent) are allowed.
- Prior history of CMV disease or CMV infection requiring anti-viral therapy
- Patients with a rash, dermatological condition, or tattoo in the area of the injection site(s) that could interfere with administration site reaction rating. (Note: The injection site(s) can be the non-dominant arm [most preferred injection site], dominant arm, or either thigh [least preferred injection site], as judged by the investigator).
- It is anticipated that the patient will be unavailable to complete the study follow-up.
- Patients who are highly sensitized or who are likely to undergo desensitization at time of transplant (e.g., donor-specific antibody titers at the local laboratory >2000).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo prophylactic placebo Three doses of placebo will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of placebo will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post- transplant patients will receive 3-6 months anti-viral prophylaxis following institutional standard. Placebo preemptive placebo Three doses of placebo will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of placebo will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post-transplant patients will be monitored per preemptive institutional standard. HB-101 vaccine preemptive HB-101 vaccine Three doses of HB-101 vaccine will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of HB-101 will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post-transplant patients will be monitored per preemptive institutional standard. HB-101 vaccine prophylactic HB-101 vaccine Three doses of HB-101 will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of HB-101 will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post- transplant patients will receive 3-6 months anti-viral prophylaxis following institutional standard. HB-101 vaccine: CMV (+) patients-Preemptive Management HB-101 vaccine Three doses of HB-101 will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of HB-101 will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post- transplant patients will follow pre-emptive management per institutional standard. HB-101 vaccine: CMV (+) patients-Prophylactic Management HB-101 vaccine Three doses of HB-101 will be administered prior to transplantation and within proximity to the time of transplantation. However, two doses of HB-101 will be sufficient for the patients to be included in the efficacy analyses if an administration of the third dose is not feasible due to transplantation timelines. Post- transplant patients will receive 3-6 months anti-viral prophylaxis following institutional standard.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events and Serious Adverse Events 15 Months Assess the number and severity of participants with adverse events and serious adverse events
Assessment of Humoral Immunogenicity Analyses 15 Months Assessment of CMV neutralizing antibody titers (NTAs) at day of Transplant defined by log10 virus neutralising unit(s)
Change of Oral Body Temperature. Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months 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.
Assessment of Cellular Immunogenicity Analyses 15 months 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
Number of Patients With Injection Site Events. 15 Months Number of patients experiencing a local or generalized injection site reaction
Change of Respiration Rate. Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months. 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.
Change of Blood Pressure. Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months 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.
- Secondary Outcome Measures
Name Time Method Time to Clinically Significant CMV Infection. 12 months 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.
Number of Participants With CMV Viremia Requiring Anti Viral Therapy 12 months 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 to Organ Rejection Up to 12 months post transplantation Measurement of time (in days) between transplantation and graft failure leading to biopsy-confirmation rejection of organ
The Duration of Anti-CMV Therapy Courses Required. 12 months Measure duration (in days) of anti-CMV therapy courses (at therapeutic doses) required in CMV seropositive (+) recipients awaiting kidney transplant.
The Time to CMV Viremia Requiring Anti Viral Therapy. 12 months 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.
Number of Participants Requiring Anti-CMV Therapy 12 months Measure the number of participants requiring anti-CMV therapy (at therapeutic doses) in CMV seropositive (+) recipients awaiting kidney transplant.
Number of Participants With Organ Rejection Up to 12 months post transplantation Assessment of number of participants with graft failure leading to biopsy-confirmation rejection of organ post transplantation.
Trial Locations
- Locations (25)
South Texas Accelerated Research
🇺🇸Dallas, Texas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
St James's University Hospital
🇬🇧Leeds, United Kingdom
Swedish Medical Center
🇺🇸Seattle, Washington, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Oslo University Hospital
🇳🇴Oslo, Norway
California Institute of Renal Research
🇺🇸La Mesa, California, United States
Universitatsklinikum Essen
🇩🇪Essen, Germany
Odense University Hospital
🇩🇰Odense, Denmark
Thomas E. Starzl Transplantation Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Centre Hospitalier Universitaire de Bordeaux Hôpital Pellegrin
🇫🇷Bordeaux Cedex, France
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Hopital Necker-Enfants Malades
🇫🇷Paris, France
CHU de Toulouse - Hospital Rangueil
🇫🇷Toulouse, France
Cardiff & Vale University Health Board
🇬🇧Cardiff, United Kingdom
The Royal Free Hospital
🇬🇧London, United Kingdom
Leicester General Hospital
🇬🇧Leicester, United Kingdom
The 1917 Clinic at UAB
🇺🇸Birmingham, Alabama, United States
UC Davis Health Systems
🇺🇸Sacramento, California, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Oklahoma University
🇺🇸Oklahoma City, Oklahoma, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Indiana University/IU Health
🇺🇸Indianapolis, Indiana, United States
University of Cincinnati (UC) - College of Medicine
🇺🇸Cincinnati, Ohio, United States
Belfast Health and Social Care Trust
🇬🇧Belfast, United Kingdom