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

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+).

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).

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; Cytomegalovirus (CMV) Infection
• Intervention / Treatment: Biological: HB-101 vaccine; Biological: 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.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Odense University Hospital
• France
  • Bordeaux Cedex, France, 33076
    • Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin
  • Paris, France, 75743
    • Hôpital Necker-Enfants Malades
  • Toulouse, France, 31400
    • CHU de Toulouse - Hospital Rangueil
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast Health and Social Care Trust
  • Cardiff, United Kingdom, CF14 4XW
    • Cardiff & Vale University Health Board
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • Leicester, United Kingdom, LE5 4PW
    • Leicester General Hospital
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • The 1917 Clinic at UAB
  • California
    • La Mesa, California, United States, 92123
      • California Institute of Renal Research
    • Sacramento, California, United States, 95817
      • UC Davis Health Systems
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/IU Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati (UC) - College of Medicine
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Thomas E. Starzl Transplantation Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • South Texas Accelerated Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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 Comparator: 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.	Biological: placebo; Saline will be used for placebo.
Experimental: 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.	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 Comparator: 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.	Biological: placebo; Saline will be used for placebo.
Experimental: 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.	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.
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Number of Patients With Injection Site Events.	Number of patients experiencing a local or generalized injection site reaction	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.	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.	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.	Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
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	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Hookipa Biotech GmbH
• Investigators: Study Director: Chief Medical Officer, Hookipa Biotech GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: May 29, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: vaccine; solid organ transplantation
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: H-100-002; 2017-005047-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No