A Study of CMV Vaccine (HB-101) in Kidney Transplant Patients

Kidney Transplantation Clinical Trial

Official title:

A Randomized, Placebo-Controlled, Phase 2 Study of HB-101, a Bivalent Cytomegalovirus (CMV) Vaccine, in CMV-Seronegative Recipient (R-) Patients Awaiting Kidney Transplantation From Living CMV-Seropositive Donors (D+).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03629080
• Other study ID #: H-100-002
• Secondary ID: 2017-005047-32
• Status: Completed
• Phase: Phase 2
• Start date: December 12, 2018
• Est. completion date: June 22, 2022

Study information

• Verified date: October 2023
• Source: Hookipa Biotech GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: June 22, 2022
• Est. primary completion date: June 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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).

Related Conditions & MeSH terms

• Cytomegalovirus (CMV) Infection
• Cytomegalovirus Infections
• Kidney Transplantation

Intervention

Biological:
• 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.
• placebo
Saline will be used for placebo.

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense
France	Centre Hospitalier Universitaire de Bordeaux Hôpital Pellegrin	Bordeaux Cedex
France	Hopital Necker-Enfants Malades	Paris
France	CHU de Toulouse - Hospital Rangueil	Toulouse
Germany	Charite Universitatsmedizin Berlin	Berlin
Germany	Universitatsklinikum Essen	Essen
Norway	Oslo University Hospital	Oslo
United Kingdom	Belfast Health and Social Care Trust	Belfast
United Kingdom	Cardiff & Vale University Health Board	Cardiff
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Leicester General Hospital	Leicester
United Kingdom	The Royal Free Hospital	London
United States	University of Colorado Hospital	Aurora	Colorado
United States	The 1917 Clinic at UAB	Birmingham	Alabama
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	South Texas Accelerated Research	Dallas	Texas
United States	Indiana University/IU Health	Indianapolis	Indiana
United States	California Institute of Renal Research	La Mesa	California
United States	Oklahoma University	Oklahoma City	Oklahoma
United States	Thomas E. Starzl Transplantation Institute	Pittsburgh	Pennsylvania
United States	UC Davis Health Systems	Sacramento	California
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hookipa Biotech GmbH

Countries where clinical trial is conducted

United States,  Denmark,  France,  Germany,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	15 Months
Primary	Assessment of Humoral Immunogenicity Analyses	Assessment of CMV neutralizing antibody titers (NTAs) at day of Transplant defined by log10 virus neutralising unit(s)	15 Months
Primary	Number of Patients With Injection Site Events.	Number of patients experiencing a local or generalized injection site reaction	15 Months
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.	Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
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.	Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months.
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.	Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
Primary	Assessment of Cellular Immunogenicity Analyses	Assessment of positive CMV IFN? ELISPOT results for pp65 and gB defined by Spot forming cells / mio PBMC per CMV Management Strategy and Doses Before Transplant	15 months
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.	12 months
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.	12 months
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.	12 months
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.	12 months
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.	12 months
Secondary	Number of Participants With Organ Rejection	Assessment of number of participants with graft failure leading to biopsy-confirmation rejection of organ post transplantation.	Up to 12 months post transplantation
Secondary	Time to Organ Rejection	Measurement of time (in days) between transplantation and graft failure leading to biopsy-confirmation rejection of organ	Up to 12 months post transplantation