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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 : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Hookipa Biotech

Brief Summary:
HB-101 is a bivalent recombinant vaccine against human CMV infection. In this phase 2 study, adult CMV-Seronegative patients awaiting kidney transplant from a CMV-Seropositive living donor will be enrolled into 1 of 2 treatment arms according to treatment intent (HB-101 or placebo) with regard to the method of CMV prevention after transplant (either preemptive or with an anti-viral prophylaxis). 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 is 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. 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, randomized, placebo controlled study will be conducted in two arms stratified by treatment intent. In arm 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 arm 1. In arm 2, patients will be randomized to receive HB-101 (2a) or placebo (2b) before transplant. Post-transplant patients will receive 3-6 months anti-viral prophylaxis following institutional standard. Approximately 100 patients will be randomized in arm 2.
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-Control, 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 : January 15, 2021
Estimated Study Completion Date : January 15, 2021

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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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."


  9. 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.


  10. 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.

  11. CMV-neutralization on MRC-5 cells; (CMV neutralization). [ Time Frame: 12 Months ]
    Analysis of CMV-neutralization on MRC-5 cells; (CMV neutralization).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



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 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. Patients must be CMV immunoglobulin G (IgG) seronegative (-) and receiving kidney for transplantation from donors who are CMV IgG seropositive (+).
  4. 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 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.

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 office@hookipabiotech.com

Locations
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United States, California
California Institute of Renal Research Recruiting
La Mesa, California, United States, 92123
Contact: Arman Faravardeh         
Principal Investigator: Arman Faravardeh         
California Pacific Medical Center Recruiting
San Francisco, California, United States, 94115
Contact: Ram V Peddi    415-600-1092    PeddiR@Sutterhealth.org   
United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Alexander Wiseman    720-848-2277    mailto:alexander.wiseman@ucdenver.edu   
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Ethan Marin    203-785-7595    ethan.marin@yale.edu   
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Beje Thomas    202-444-3700    beje.thomas@gunet.georgetown.edu   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: David Wojciechowski    617-724-9673    mailto:dwojciechowski@mgh.harvard.edu   
United States, Ohio
The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Rita Alloway         
Principal Investigator: Rita Alloway         
University of Cincinnati (UC) - College of Medicine Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Rita Alloway         
Principal Investigator: Rita Alloway         
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Kenneth Chavin    216-844-2858    Kenneth.Chavin@UHhospitals.org   
United States, Utah
Intermountain Medical Center Recruiting
Murray, Utah, United States, 84157
Contact: Srinivas Titte    801-507-3380    Titte.srinivas@imail.org   
United States, Washington
Swedish Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Nelson Goes    206-386-3660    mailto:nelson.goes@swedish.org   
Belgium
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium, 1200
Contact: Eric Goffin         
Principal Investigator: Eric Goffin         
United Kingdom
Belfast City Hospital Recruiting
Belfast, United Kingdom, BT9 7AB
Contact: Christopher Hill    44 (0)2895043216    christopher.hill@belfasttrust.hscni.net   
Southmead Hospital Recruiting
Bristol, United Kingdom, BS105NB
Contact: Rommel Ravanan    01174147698    Rommel.ravanan@nbt.nhs.uk   
St James's University Hospital Recruiting
Leeds, United Kingdom, LS9 7TF
Contact: Sunil Daga       sunildaga@nhs.net   
The Royal Free Hospital Recruiting
London, United Kingdom, NW3 2QG
Contact: Mark Harber    +442077940500    mark.harber@nhs.net   
University of Manchester Royal Infirmary Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Muir Morton       Muir.Morton@mft.nhs.uk   
Sponsors and Collaborators
Hookipa Biotech
Investigators
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Principal Investigator: Igor Matushansky Hookipa Biotech

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Responsible Party: Hookipa Biotech
ClinicalTrials.gov Identifier: NCT03629080     History of Changes
Other Study ID Numbers: H-100-002
2017-005047-32 ( EudraCT Number )
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019
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:
solid organ transplantation
vaccine

Additional relevant MeSH terms:
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Vaccines
Immunologic Factors
Physiological Effects of Drugs