Cytomegalovirus (CMV) Infection, Kidney Transplantation
Conditions
Keywords
solid organ transplantation, vaccine
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.
Interventions
BIOLOGICALHB-101 vaccine
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.
BIOLOGICALplacebo
Saline will be used for placebo.
Sponsors
Hookipa Biotech GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The participants, investigators and care providers (study site personnel) will be blinded.
Intervention model description
This phase 2 study will be conducted in three groups stratified by treatment intent. In Group 1, patients will be randomized to receive HB-101 (1a) or placebo (1b) and followed preemptively post-transplant. Approximately 50 patients will be randomized in Group 1. In Group 2, patients will be randomized to receive HB-101 (2a) or placebo (2b) before transplant. Post-transplant patients will receive 3-6 months of anti-viral prophylaxis following institutional standards. Approximately 100 patients will be randomized in Group 2. In Group 3, all patients will receive HB-101 (open label) vaccination(s) prior to their transplant surgery. Post-transplant CMV management will follow either preemptive or prophylactic care as defined at study enrollment by the investigator and institutional standards. Approximately 25 patients will be randomized in Group 3.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Patients who meet all of the following key inclusion criteria will be eligible to participate in the study: 1. Male or female patients 18 years of age or older. 2. Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards. 3. 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 (+). 4. 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 (+). 5. Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator.
Exclusion criteria
Patients who meet any of the following key criteria will be excluded from the study: 1. Patients planning to undergo multi-organ transplantation. 2. Patients participating in another interventional clinical study. 3. Previous vaccination with an investigational CMV vaccine. 4. 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. 5. 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. 6. Prior history of CMV disease or CMV infection requiring anti-viral therapy 7. 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). 8. It is anticipated that the patient will be unavailable to complete the study follow-up. 9. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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) |
| Number of Patients With Injection Site Events. | 15 Months | Number of patients experiencing a local or generalized injection site reaction |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Denmark, France, Germany, Norway, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HB-101 Vaccine Preemptive 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: 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. | 12 |
| Placebo Preemptive 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.
placebo: Saline will be used for placebo. | 5 |
| HB-101 Vaccine Prophylactic 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: 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. | 35 |
| Placebo Prophylactic 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: Saline will be used for placebo. | 17 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management 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: 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. | 10 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management 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: 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. | 4 |
| Total | 83 |
Baseline characteristics
| Characteristic | Placebo Preemptive | HB-101 Vaccine Prophylactic | Placebo Prophylactic | HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | HB-101 Vaccine: CMV (+) Patients-Preemptive Management | HB-101 Vaccine Preemptive | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 31 Participants | 16 Participants | 9 Participants | 4 Participants | 9 Participants | 71 Participants |
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.45 | 47.3 years STANDARD_DEVIATION 15.13 | 45.5 years STANDARD_DEVIATION 13.99 | 49.5 years STANDARD_DEVIATION 11.92 | 48.3 years STANDARD_DEVIATION 6.99 | 47.5 years STANDARD_DEVIATION 15.9 | 48.31 years STANDARD_DEVIATION 14.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 29 Participants | 16 Participants | 6 Participants | 2 Participants | 12 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 5 Participants | 28 Participants | 17 Participants | 8 Participants | 4 Participants | 11 Participants | 73 Participants |
| Sex: Female, Male Female | 0 Participants | 6 Participants | 6 Participants | 3 Participants | 1 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Male | 5 Participants | 29 Participants | 11 Participants | 7 Participants | 3 Participants | 8 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 4 | 1 / 34 | 0 / 17 | 0 / 10 | 0 / 4 |
| other Total, other adverse events | 6 / 11 | 3 / 4 | 22 / 34 | 12 / 17 | 6 / 10 | 3 / 4 |
| serious Total, serious adverse events | 5 / 11 | 2 / 4 | 14 / 34 | 5 / 17 | 2 / 10 | 2 / 4 |
Outcome results
Primary
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
Population: The modified intent to treat population includes all participants who received a kidney transplant and at least 2 doses of study drug prior to kidney transplant.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (2 Doses) | 83.0 SFC/10e6 PBMC |
| HB-101 Vaccine Preemptive | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (2 Doses) | 78.0 SFC/10e6 PBMC |
| HB-101 Vaccine Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (2 Doses) | 30.7 SFC/10e6 PBMC |
| HB-101 Vaccine Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (3 Doses) | 95.3 SFC/10e6 PBMC |
| HB-101 Vaccine Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (2 Doses) | 37.5 SFC/10e6 PBMC |
| HB-101 Vaccine Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (3 Doses) | 59.3 SFC/10e6 PBMC |
| Placebo Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (2 Doses) | 15.0 SFC/10e6 PBMC |
| Placebo Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (3 Doses) | 15.0 SFC/10e6 PBMC |
| Placebo Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (3 Doses) | 15.0 SFC/10e6 PBMC |
| Placebo Prophylactic | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (2 Doses) | 11.0 SFC/10e6 PBMC |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (3 Doses) | 4145.0 SFC/10e6 PBMC |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (3 Doses) | 615.0 SFC/10e6 PBMC |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT gB (3 Doses) | 1840.0 SFC/10e6 PBMC |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Assessment of Cellular Immunogenicity Analyses | CMV ELISPOT pp65 (3 Doses) | 3897.0 SFC/10e6 PBMC |
Primary
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
Population: The modified intent to treat population includes all participants who received a kidney transplant and at least 2 doses of study drug prior to kidney transplant.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 0.8 log10 neutralizing titers |
| HB-101 Vaccine Preemptive | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 1.1 log10 neutralizing titers |
| Placebo Preemptive | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 0.6 log10 neutralizing titers |
| Placebo Preemptive | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 0.6 log10 neutralizing titers |
| HB-101 Vaccine Prophylactic | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 0.8 log10 neutralizing titers |
| HB-101 Vaccine Prophylactic | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 1.4 log10 neutralizing titers |
| Placebo Prophylactic | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 0.8 log10 neutralizing titers |
| Placebo Prophylactic | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 0.6 log10 neutralizing titers |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 2.6 log10 neutralizing titers |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 2.7 log10 neutralizing titers |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Assessment of Humoral Immunogenicity Analyses | CMV Neut (2 Doses) | 2.5 log10 neutralizing titers |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Assessment of Humoral Immunogenicity Analyses | CMV Neut (3 Doses) | 2.5 log10 neutralizing titers |
Primary
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
Population: Only participants having received all 3 doses are analyzed and presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HB-101 Vaccine Preemptive | Change of Blood Pressure. | Diastolic | 0.5 mmHg | Standard Deviation 5.74 |
| HB-101 Vaccine Preemptive | Change of Blood Pressure. | Systolic | -5.5 mmHg | Standard Deviation 12.61 |
| Placebo Preemptive | Change of Blood Pressure. | Diastolic | 2.0 mmHg | Standard Deviation 0 |
| Placebo Preemptive | Change of Blood Pressure. | Systolic | 11.0 mmHg | Standard Deviation 0 |
| HB-101 Vaccine Prophylactic | Change of Blood Pressure. | Diastolic | 2.6 mmHg | Standard Deviation 9.55 |
| HB-101 Vaccine Prophylactic | Change of Blood Pressure. | Systolic | 5.4 mmHg | Standard Deviation 14.36 |
| Placebo Prophylactic | Change of Blood Pressure. | Diastolic | 1.3 mmHg | Standard Deviation 6.47 |
| Placebo Prophylactic | Change of Blood Pressure. | Systolic | 2.7 mmHg | Standard Deviation 19.81 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Change of Blood Pressure. | Diastolic | 6.0 mmHg | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Change of Blood Pressure. | Systolic | 5.0 mmHg | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Change of Blood Pressure. | Diastolic | 6.0 mmHg | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Change of Blood Pressure. | Systolic | 2.0 mmHg | Standard Deviation 2.83 |
Primary
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
Population: Only participants having received all 3 doses are analyzed and presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Change of Oral Body Temperature. | -0.0 Degrees Celcius | Standard Deviation 0.4 |
| Placebo Preemptive | Change of Oral Body Temperature. | -0.1 Degrees Celcius | Standard Deviation 0 |
| HB-101 Vaccine Prophylactic | Change of Oral Body Temperature. | 0.2 Degrees Celcius | Standard Deviation 0.6 |
| Placebo Prophylactic | Change of Oral Body Temperature. | -0.3 Degrees Celcius | Standard Deviation 0.26 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Change of Oral Body Temperature. | 0.6 Degrees Celcius | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Change of Oral Body Temperature. | -0.2 Degrees Celcius | Standard Deviation 0.57 |
Primary
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.
Population: Only participants having received all 3 doses are analyzed and presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Change of Respiration Rate. | 0.5 breaths/minute | Standard Deviation 5.26 |
| Placebo Preemptive | Change of Respiration Rate. | 0.0 breaths/minute | Standard Deviation 0 |
| HB-101 Vaccine Prophylactic | Change of Respiration Rate. | 0.2 breaths/minute | Standard Deviation 2.56 |
| Placebo Prophylactic | Change of Respiration Rate. | -0.6 breaths/minute | Standard Deviation 2.7 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Change of Respiration Rate. | 2.0 breaths/minute | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Change of Respiration Rate. | -4.0 breaths/minute | Standard Deviation 8.49 |
Primary
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
Population: For the safety population: In groups HB-101 prophylactic, Placebo prophylactic and placebo preemptive each 1 subject was excluded for reason being not receiving any study drug. One patient who was randomized to HB-101, received 2 doses of placebo and as a result, this patient was included in the placebo
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 5 Participants |
| HB-101 Vaccine Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 0 Participants |
| HB-101 Vaccine Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 6 Participants |
| Placebo Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 2 Participants |
| Placebo Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 0 Participants |
| Placebo Preemptive | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 3 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 0 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 23 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 14 Participants |
| Placebo Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 12 Participants |
| Placebo Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 5 Participants |
| Placebo Prophylactic | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 0 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 6 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants With Adverse Events and Serious Adverse Events | Serious Adverse Events | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events | 3 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants With Adverse Events and Serious Adverse Events | Grade 3 or Higher Adverse Events | 2 Participants |
Primary
Number of Patients With Injection Site Events.
Number of patients experiencing a local or generalized injection site reaction
Time frame: 15 Months
Population: For the safety population: In groups HB-101 prophylactic, Placebo prophylactic and placebo preemptive each 1 subject was excluded for reason being not receiving any study drug. One patient who was randomized to HB-101, received 2 doses of placebo and as a result, this patient was included in the placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HB-101 Vaccine Preemptive | Number of Patients With Injection Site Events. | 1 Participants |
| Placebo Preemptive | Number of Patients With Injection Site Events. | 0 Participants |
| HB-101 Vaccine Prophylactic | Number of Patients With Injection Site Events. | 4 Participants |
| Placebo Prophylactic | Number of Patients With Injection Site Events. | 4 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Patients With Injection Site Events. | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Patients With Injection Site Events. | 1 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HB-101 Vaccine Preemptive | Number of Participants Requiring Anti-CMV Therapy | 5 Participants |
| Placebo Preemptive | Number of Participants Requiring Anti-CMV Therapy | 2 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants Requiring Anti-CMV Therapy | 4 Participants |
| Placebo Prophylactic | Number of Participants Requiring Anti-CMV Therapy | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants Requiring Anti-CMV Therapy | 1 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants Requiring Anti-CMV Therapy | 1 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HB-101 Vaccine Preemptive | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 5 Participants |
| Placebo Preemptive | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 2 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 5 Participants |
| Placebo Prophylactic | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 2 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 1 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants With CMV Viremia Requiring Anti Viral Therapy | 1 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HB-101 Vaccine Preemptive | Number of Participants With Organ Rejection | 1 Participants |
| Placebo Preemptive | Number of Participants With Organ Rejection | 0 Participants |
| HB-101 Vaccine Prophylactic | Number of Participants With Organ Rejection | 3 Participants |
| Placebo Prophylactic | Number of Participants With Organ Rejection | 1 Participants |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Number of Participants With Organ Rejection | 0 Participants |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Number of Participants With Organ Rejection | 0 Participants |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HB-101 Vaccine Preemptive | The Duration of Anti-CMV Therapy Courses Required. | 154.2 days | Standard Deviation 77.43 |
| Placebo Preemptive | The Duration of Anti-CMV Therapy Courses Required. | 89.0 days | Standard Deviation 91.92 |
| HB-101 Vaccine Prophylactic | The Duration of Anti-CMV Therapy Courses Required. | 87.0 days | Standard Deviation 47.17 |
| Placebo Prophylactic | The Duration of Anti-CMV Therapy Courses Required. | 72.0 days | Standard Deviation 24.04 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | The Duration of Anti-CMV Therapy Courses Required. | 198.0 days | — |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | The Duration of Anti-CMV Therapy Courses Required. | 20.0 days | — |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HB-101 Vaccine Preemptive | The Time to CMV Viremia Requiring Anti Viral Therapy. | 53.6 days | Standard Deviation 25.13 |
| Placebo Preemptive | The Time to CMV Viremia Requiring Anti Viral Therapy. | 129.0 days | Standard Deviation 124.45 |
| HB-101 Vaccine Prophylactic | The Time to CMV Viremia Requiring Anti Viral Therapy. | 259.2 days | Standard Deviation 21.74 |
| Placebo Prophylactic | The Time to CMV Viremia Requiring Anti Viral Therapy. | 259.0 days | Standard Deviation 18.38 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | The Time to CMV Viremia Requiring Anti Viral Therapy. | 171.0 days | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | The Time to CMV Viremia Requiring Anti Viral Therapy. | 15.0 days | Standard Deviation 0 |
Secondary
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
Population: the number of participants analyzed differs from the total number of participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HB-101 Vaccine Preemptive | Time to Clinically Significant CMV Infection. | CMV Infection | 50.2 days | Standard Deviation 24.05 |
| HB-101 Vaccine Preemptive | Time to Clinically Significant CMV Infection. | CMV Syndrome | 66.0 days | Standard Deviation 33.94 |
| HB-101 Vaccine Preemptive | Time to Clinically Significant CMV Infection. | CMV Disease | 62.5 days | Standard Deviation 38.89 |
| Placebo Preemptive | Time to Clinically Significant CMV Infection. | CMV Infection | 83.0 days | Standard Deviation 69.3 |
| HB-101 Vaccine Prophylactic | Time to Clinically Significant CMV Infection. | CMV Infection | 256.2 days | Standard Deviation 20.82 |
| HB-101 Vaccine Prophylactic | Time to Clinically Significant CMV Infection. | CMV Syndrome | 277.0 days | Standard Deviation 0 |
| HB-101 Vaccine Prophylactic | Time to Clinically Significant CMV Infection. | CMV Disease | 277.0 days | Standard Deviation 0 |
| Placebo Prophylactic | Time to Clinically Significant CMV Infection. | CMV Infection | 248.0 days | Standard Deviation 84.59 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Time to Clinically Significant CMV Infection. | CMV Infection | 171.0 days | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Prophylactic Management | Time to Clinically Significant CMV Infection. | CMV Disease | 0 days | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Time to Clinically Significant CMV Infection. | CMV Disease | 0 days | Standard Deviation 0 |
| HB-101 Vaccine: CMV (+) Patients-Preemptive Management | Time to Clinically Significant CMV Infection. | CMV Infection | 15.0 days | Standard Deviation 0 |
Secondary
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
Population: Number of participants analyzed is based on Secondary Outcome Measure #13. Only participants with organ rejection can be analyzed for this Outcome Measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HB-101 Vaccine Preemptive | Time to Organ Rejection | 59.0 days | — |
| HB-101 Vaccine Prophylactic | Time to Organ Rejection | 126.3 days | Standard Deviation 193.81 |
| Placebo Prophylactic | Time to Organ Rejection | 34.0 days | — |