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

NCT03629080 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: H-100-0022017-005047-32
• Study Type: interventional
• Target: 83
• Locations: 6 countries
• Sites: 25

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).

Conditions

Cytomegalovirus (CMV) Infection; Kidney Transplantation

Keywords

solid organ transplantation; vaccine

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (7)

• Time to Clinically Significant CMV Infection.

  12 months

• Number of Participants With CMV Viremia Requiring Anti Viral Therapy

  12 months

• The Time to CMV Viremia Requiring Anti Viral Therapy.

  12 months

• Number of Participants Requiring Anti-CMV Therapy

  12 months

• The Duration of Anti-CMV Therapy Courses Required.

  12 months

Study Arms (6)

HB-101 vaccine preemptive

EXPERIMENTAL

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

Placebo preemptive

PLACEBO COMPARATOR

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

HB-101 vaccine prophylactic

EXPERIMENTAL

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

Placebo prophylactic

PLACEBO COMPARATOR

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

HB-101 vaccine: CMV (+) patients-Prophylactic Management

EXPERIMENTAL

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 vaccine: CMV (+) patients-Preemptive Management

EXPERIMENTAL

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

Interventions

HB-101 vaccine BIOLOGICAL

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.

HB-101 vaccine preemptive; HB-101 vaccine prophylactic; HB-101 vaccine: CMV (+) patients-Preemptive Management; HB-101 vaccine: CMV (+) patients-Prophylactic Management

placebo BIOLOGICAL

Saline will be used for placebo.

Placebo preemptive; Placebo prophylactic

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years of age or older.
• Patients must be eligible to undergo kidney transplantation from a living donor as per institutional standards.
• 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 (+).
• 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 (+).
• Patients who would comply with the requirements of this protocol (e.g., return for follow up visits), as judged by the investigator.

You may not qualify if:

• Patients who meet any of the following key criteria will be excluded from the study:
• Patients planning to undergo multi-organ transplantation.
• Patients participating in another interventional clinical study.
• Previous vaccination with an investigational CMV vaccine.
• 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.
• 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.
• Prior history of CMV disease or CMV infection requiring anti-viral therapy
• 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).
• It is anticipated that the patient will be unavailable to complete the study follow-up.
• 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).

Sponsors & Collaborators

• Hookipa Biotech GmbH: lead

Study Sites (25)

The 1917 Clinic at UAB

Birmingham, Alabama, 35205, United States

Location

California Institute of Renal Research

La Mesa, California, 92123, United States

Location

UC Davis Health Systems

Sacramento, California, 95817, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Indiana University/IU Health

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati (UC) - College of Medicine

Cincinnati, Ohio, 45267, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oklahoma University

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas E. Starzl Transplantation Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

South Texas Accelerated Research

Dallas, Texas, 75390, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Centre Hospitalier Universitaire de Bordeaux Hôpital Pellegrin

Bordeaux, 33076, France

Location

Hopital Necker-Enfants Malades

Paris, 75743, France

Location

CHU de Toulouse - Hospital Rangueil

Toulouse, 31400, France

Location

Charite Universitatsmedizin Berlin

Berlin, 10117, Germany

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Oslo University Hospital

Oslo, 0424, Norway

Location

Belfast Health and Social Care Trust

Belfast, BT9 7AB, United Kingdom

Location

Cardiff & Vale University Health Board

Cardiff, CF14 4XW, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester General Hospital

Leicester, LE5 4PW, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Hookipa Front Desk
• Organization: Hookipa Biotech GmbH

office@hookipapharma.com

+43 1 890 63 60 0

Study Officials

• Chief Medical Officer

  Hookipa Biotech GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The participants, investigators and care providers (study site personnel) will be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 29, 2018
• First Posted: August 14, 2018
• Study Start: December 12, 2018
• Primary Completion: June 22, 2022
• Study Completion: June 22, 2022
• Last Updated: October 26, 2023
• Results First Posted: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5); US (13); DE (2); DK (1); FR (3); NO (1)