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

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ClinicalTrials.gov Identifier: NCT03629080
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Cytomegalovirus (CMV) Infection Kidney Transplantation Biological: HB-101 vaccine Biological: placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The participants, investigators and care providers (study site personnel) will be blinded.
Primary Purpose: Prevention
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+).
Actual Study Start Date : December 12, 2018
Estimated Primary Completion Date : October 7, 2022
Estimated Study Completion Date : October 7, 2022

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. The safety of HB-101. [ Time Frame: 15 Months ]
    Assess the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).

  2. The immunogenicity of HB-101. [ Time Frame: 15 Months ]
    Central statistics will be performed for the following immunogenicity parameters: CMV neut, CMV ELISPOT pp65, and CMV ELISPOT gB to determine immunogenicity of HB-101.

  3. The reactogenicity of HB-101. [ Time Frame: 15 Months ]
    Assess the incidence and severity of localized or generalized injection site reactions to determine the reactogenicity of HB-101.

  4. Measure Oral Body Temperature. [ Time Frame: up to 3 months ]
    Measure Oral Body Temperature in degrees Celsius prior to study drug administrations and seven days after. Three doses of the study drug will be administered up to 3 months after randomization.

  5. Measure Respiration Rate. [ Time Frame: up to 3 months ]
    Measure respiration rate in breaths per minute prior to study drug administration and seven days after. Three doses of the study drug will be administered up to 3 months after randomization.

  6. Measure Blood Pressure. [ Time Frame: up to 3 months ]
    Measure Blood Pressure (diastolic and systolic) in mmHg prior to study drug administration and seven days after. Three doses of the study drug will be administered up to 3 months after randomization.

  7. Measure Weight. [ Time Frame: up to 3 months ]
    Measure Weight in Kilograms prior to study drug administration and seven days after. Three doses of the study drug will be administered up to 3 months after randomization.

  8. Cellular immunogenicity analyses the day of transplant and 3, 6 and 9 months after the transplant and 12 months at the end of study visit. [ Time Frame: 12 months ]

    Cellular immunogenicity analyses will be conducted at the day of transplant, and 3, 6, 9 months after the transplant and 12 months at the end of study visit (a total of 12 months post-transplant follow up).

    Cellular immunogenicity analyses of CMV pp65-specific interferon γ (IFN-γ) and CMV gB-specific IFN-γ.


  9. Humoral immunogenicity analyses prior to the first dose of the study drug (3 months prior to transplant), on the day of transplant, and at the end of study visit (up to 12 months post-transplant follow-up to a total of 15 months). [ Time Frame: 15 months ]
    Analysis of CMV-neutralization on MRC-5 cells.


Secondary Outcome Measures :
  1. Time to clinically significant CMV infection. [ Time Frame: 12 months ]
    Measure the time to clinically significant CMV infection, CMV disease, CMV syndrome, quantifiable CMV DNAemia, peak CMV DNAemia level, duration of CMV DNAemia above the limit of quantitation, graft failure, and organ rejection for CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and followed by CMV preemptive therapy post-transplant.

  2. Incidence to clinically significant CMV infection. [ Time Frame: 12 months ]
    Measure the incidence to clinically significant CMV infection, CMV disease, CMV syndrome, quantifiable CMV DNAemia, peak CMV DNAemia level, duration of CMV DNAemia above the limit of quantitation, graft failure, and organ rejection for CMV seronegative (-) recipients awaiting kidney transplantation from a CMV seropositive (+) donor and followed by CMV preemptive therapy post-transplant.

  3. The incidence of CMV viremia requiring anti viral therapy. [ Time Frame: 12 months ]
    Measure the incidence of 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.

  4. The time to CMV viremia requiring anti viral therapy. [ Time Frame: 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.

  5. The incidence of anti-CMV therapy courses required. [ Time Frame: 12 months ]
    Measure the incidence of anti-CMV therapy courses (at therapeutic doses) required in CMV seropositive (+) recipients awaiting kidney transplant.

  6. The duration of anti-CMV therapy courses required. [ Time Frame: 12 months ]
    Measure duration (in days) of anti-CMV therapy courses (at therapeutic doses) required in CMV seropositive (+) recipients awaiting kidney transplant.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03629080


Contacts
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Contact: General Hookipa contact +43 1 890 6360 (EU) office@hookipabiotech.com
Contact: General Hookipa contact +1-322-207-4590 (US)

Locations
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Sponsors and Collaborators
Hookipa Biotech GmbH
Investigators
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Principal Investigator: Igor Matushansky Hookipa Biotech GmbH
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Responsible Party: Hookipa Biotech GmbH
ClinicalTrials.gov Identifier: NCT03629080    
Other Study ID Numbers: H-100-002
2017-005047-32 ( EudraCT Number )
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: February 26, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hookipa Biotech GmbH:
solid organ transplantation
vaccine