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Trial record 6 of 12 for:    CMV | Berlin, Germany

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03629080
Recruitment Status : Active, not recruiting
First Posted : August 14, 2018
Last Update Posted : October 12, 2021
Sponsor:
Information provided by (Responsible Party):
Hookipa Biotech GmbH

Tracking Information
First Submitted Date  ICMJE May 29, 2018
First Posted Date  ICMJE August 14, 2018
Last Update Posted Date October 12, 2021
Actual Study Start Date  ICMJE December 12, 2018
Estimated Primary Completion Date June 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • The safety of HB-101. [ Time Frame: 15 Months ]
    Assess the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • Incidence of adverse events from the time of first injection of study drug (3 months prior to transplant) up to 12 months post-transplant follow-up. [ Time Frame: 15 months ]
    For pre-transplant when study is administered: Evaluate the incidence of adverse events including clinical laboratory test variables (Complete Blood Count with differential, liver function tests, renal function tests) from the time of first injection of study drug up through 30 days after the last injection of study drug.
  • Incidence of adverse events of special interest from post-transplant (graft rejection, CMV syndrome and disease assessment) to the End of Study Visit. [ Time Frame: 15 months ]
    Evaluate the incidence of adverse events of special interest from post-transplant (graft rejection, CMV syndrome and disease) to the End of Study Visit.
  • Measure Oral Body Temperature. [ Time Frame: 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.
  • Measure Heart Rate. [ Time Frame: 3 Months ]
    Measure heart rate in beats 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.
  • Measure Respiration Rate. [ Time Frame: 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.
  • Measure Blood Pressure. [ Time Frame: 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.
  • Measure Weight. [ Time Frame: 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.
  • Assessment of local signs/symptoms of reactogenicity. [ Time Frame: 3 Months ]
    Assessment of local signs/symptoms of reactogenicity (administration site pain, tenderness, induration, erythema, redness, pruritus, or swelling) on treatment days for at least 60 minutes after study drug administration, and 7 days post-administration of study drug. Three doses of the study drug will be administered up to 3 months after randomization. The severity of local signs/symptoms of reactogenity will be assigned as grade 1- 4, where increasing grade relates to increased severity, following the criteria listed in the FDA "Guidance for Industry: Toxicity Grading Scale for Healthy Adults and Adolescent Volunteers Enrolled in Preventative Vaccine Trials."
  • Cellular immunogenicity analyses the day of transplant and 3, 6 and 9 months after the transplant and 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 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), CMV gB-specific IFN-γ, CMV intracellular cytokine staining (ICS) pp65, CMV ICS gB, LCMV ELISPOT NP.
  • 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). [ Time Frame: 15 Months ]
    Analysis of CMV-neutralization on MRC-5 cells and humoral immunogenicity of LCMV neutralizing using ELISPOT assay.
  • CMV-neutralization on MRC-5 cells; (CMV neutralization). [ Time Frame: 12 Months ]
    Analysis of CMV-neutralization on MRC-5 cells; (CMV neutralization).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2021)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • The incidence of CMV DNAemia to assess the efficacy of HB-101 through 12 months after transplant. [ Time Frame: 12 months ]
    Assess the incidence of CMV infection for 12 months since the day of transplant. The incidence will be assessed using polymerase chain reaction.
  • The use of anti-CMV antivirals through 12 months after transplant. [ Time Frame: 12 Months ]
    Assess the use of antivirals used by measuring occurrence of anti-CMV antiviral therapy course for 12 months since the day of transplant.
  • The magnitude of CMV DNAemia to assess the efficacy of HB-101 through 12 months after transplant. [ Time Frame: 12 Months ]
    Assess the magnitude of CMV infection for 12 months since the day of transplant. The magnitude will be assessed using polymerase chain reaction.
  • The duration of CMV DNAemia to assess the efficacy of HB-101 through 12 months after transplant. [ Time Frame: 12 Months ]
    Assess the duration of CMV infection for 12 months since the day of transplant. The duration will be assessed using polymerase chain reaction.
  • The incidence of courses of CMV anti-viral therapy through 12 months after transplant. [ Time Frame: 12 months ]
    The efficacy of the administration of at least two doses of HB-101 compared to that of placebo in decreasing the use of anti-virals at treatment dose. The incidence of courses of CMV anti-viral therapy through 12 months after transplant will be assessed.
  • The duration of courses of CMV anti-viral therapy through 12 months after transplant. [ Time Frame: 12 Months ]
    The efficacy of the administration of at least two doses of HB-101 compared to that of placebo in decreasing the use of anti-virals at treatment dose. The duration of courses of CMV anti-viral therapy through 12 months after transplant will be assessed.
  • The number of courses of CMV anti-viral therapy through 12 months after transplant. [ Time Frame: 12 Months ]
    The efficacy of the administration of at least two doses of HB-101 compared to that of placebo in decreasing the use of anti-virals at treatment dose. The number of courses of CMV anti-viral therapy through 12 months after transplant will be assessed.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of CMV Vaccine (HB-101) in Kidney Transplant Patients
Official Title  ICMJE 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+).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Cytomegalovirus (CMV) Infection
  • Kidney Transplantation
Intervention  ICMJE
  • 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.
  • Biological: placebo
    Saline will be used for placebo.
Study Arms  ICMJE
  • 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.
    Intervention: Biological: HB-101 vaccine
  • 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.
    Intervention: Biological: 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.
    Intervention: Biological: HB-101 vaccine
  • 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.
    Intervention: Biological: 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.
    Intervention: Biological: HB-101 vaccine
  • 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.
    Intervention: Biological: HB-101 vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 2, 2021)
83
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2018)
150
Estimated Study Completion Date  ICMJE June 28, 2022
Estimated Primary Completion Date June 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Denmark,   France,   Norway,   United Kingdom,   United States
Removed Location Countries Austria,   Belgium,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT03629080
Other Study ID Numbers  ICMJE H-100-002
2017-005047-32 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hookipa Biotech GmbH
Study Sponsor  ICMJE Hookipa Biotech GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Igor Matushansky Hookipa Biotech GmbH
PRS Account Hookipa Biotech GmbH
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP