Clinical trial NCT03629080: A Study of CMV Vaccine (HB-101) in Kidney Transplant Patients
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+).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus (CMV) Infection
Kidney Transplantation
Keywords: solid organ transplantation
vaccine
Lead sponsor: Hookipa Biotech GmbH
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility 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).

Primary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: 15 Months
measure: Assessment of Humoral Immunogenicity Analyses
timeFrame: 15 Months
measure: Number of Patients With Injection Site Events.
timeFrame: 15 Months
measure: Change of Oral Body Temperature.
timeFrame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
measure: Change of Respiration Rate.
timeFrame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months.
measure: Change of Blood Pressure.
timeFrame: Change from Baseline to 7 days after study drug administration of Dose 3. Three (3) months
measure: Assessment of Cellular Immunogenicity Analyses
timeFrame: 15 months
Secondary outcomes:
measure: Time to Clinically Significant CMV Infection.
timeFrame: 12 months
measure: Number of Participants With CMV Viremia Requiring Anti Viral Therapy
timeFrame: 12 months
measure: The Time to CMV Viremia Requiring Anti Viral Therapy.
timeFrame: 12 months
measure: Number of Participants Requiring Anti-CMV Therapy
timeFrame: 12 months
measure: The Duration of Anti-CMV Therapy Courses Required.
timeFrame: 12 months
measure: Number of Participants With Organ Rejection
timeFrame: Up to 12 months post transplantation
measure: Time to Organ Rejection
timeFrame: Up to 12 months post transplantation
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The 1917 Clinic at UAB
state: Alabama
city: La Mesa
country: United States
facility: California Institute of Renal Research
state: California
city: Sacramento
country: United States
facility: UC Davis Health Systems
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University/IU Health
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati (UC) - College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University
state: Oklahoma
city: Pittsburgh
country: United States
facility: Thomas E. Starzl Transplantation Institute
state: Pennsylvania
city: Dallas
country: United States
facility: South Texas Accelerated Research
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Odense
country: Denmark
facility: Odense University Hospital
city: Bordeaux Cedex
country: France
facility: Centre Hospitalier Universitaire de Bordeaux Hôpital Pellegrin
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Toulouse
country: France
facility: CHU de Toulouse - Hospital Rangueil
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Cardiff
country: United Kingdom
facility: Cardiff & Vale University Health Board
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: The Royal Free Hospital
Study officials:
affiliation: Hookipa Biotech GmbH
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: