Trial to Evaluate Safety and Immunogenicity of a Vaccine Against HCMV

• ClinicalTrials.gov Identifier: NCT02798692
• Recruitment Status: Completed
• First Posted: June 14, 2016
• Last Update Posted: April 3, 2018
• Sponsor: Hookipa Biotech
• Collaborator: Centre for Vaccinology Ghent - CEVAC
• Information provided by (Responsible Party): Hookipa Biotech

Study Description

Brief Summary:

The objectives of this first-in-human is to evaluate the safety and the immunogenicity of three administrations of a bivalent vaccine candidate against human cytomegalovirus, at three different dose levels.

Condition or disease	Intervention/treatment	Phase
Cytomegalovirus Infection	Biological: Low dose HB-101; Biological: Medium dose HB-101; Biological: High dose HB-101; Biological: Placebo	Phase 1

Detailed Description:

Hookipa Biotech AG is developing a replication-deficient lymphocytic choriomeningitis virus (rLCMV) vector platform. HB-101 is a bivalent vaccine containing two recombinant, replication-deficient lymphocytic choriomeningitis virus (rLCMV) vectors, one expressing the pp65 protein of the human cytomegalovirus (HCMV) and one expressing the gB protein of human cytomegalovirus (HCMV).

This Phase 1 will enroll three successive cohorts of 18 healthy volunteers. Each cohort will receive either a low dose, a middle dose or a high dose of the vaccine (n=14 volunteers), or placebo (n=4). A DSMB will review the safety data for the low dose cohort, before progressing to the middle, and so before high dose. Eight DSMB meetings have been planned for the whole study.

The subjects will be followed up to 12 months post first administration.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized, Placebo-controlled, Double-blind Phase I Dose-escalating Trial to Evaluate the Safety and Immunogenicity of a Vaccine Against Human Cytomegalovirus
• Actual Study Start Date: June 2016
• Actual Primary Completion Date: May 2017
• Actual Study Completion Date: March 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Low dose HB-101 group; Intervention:Three administrations of a low dose of HB-101	Biological: Low dose HB-101; Three intra muscular administrations at Day 0, Month 1 and Month 3
Active Comparator: Medium dose HB-101 group; Intervention:Three administrations of a middle dose of HB-101.	Biological: Medium dose HB-101; Three intra muscular administrations at Day 0, Month 1 and Month 3
Active Comparator: High dose HB101 group; Intervention:Three administrations of a high dose of HB-101.	Biological: High dose HB-101; Three intra muscular administrations at Day 0, Month 1 and Month 3
Placebo Comparator: Placebo group; Intervention:Three administrations of placebo (diluent)	Biological: Placebo; Three intra muscular administrations at Day 0, Month 1 and Month 3. The diluent is used as placebo.

Outcome Measures

Primary Outcome Measures :

1. Safety primary outcome (local solicited symptoms) [ Time Frame: Day 0 to Day 7 after each administration ]
   Local solicited symptoms will be assessed by diary card and scripted questions for 7 days after each administration: administration site pain, induration, erythema, pruritus and swelling
2. Safety primary outcome (general solicited symptoms) [ Time Frame: Day 0 to Day 7 after each administration ]
   General solicited symptoms will be assessed by diary card and scripted questions for 7 days after each administration: malaise, fatigue, body temperature (measured axillary), generalized myalgia.
3. Safety primary outcome (Unsolicited AE´s) [ Time Frame: From Day 0 to Month 4 ]
   Unsolicited AEs will be recorded through open-ended general inquiries
4. Safety primary outcome (SAEs and pregnancies) [ Time Frame: From Day 0 to Month 12 ]
   SAEs and pregnancies will be recorded during the whole study
5. Safety primary outcome (Vital signs) [ Time Frame: From Day 0 to Month 12 ]
   Vital signs (blood pressure, heart rate and body temperature)
6. Safety primary outcome (physical examination) [ Time Frame: From Day 0 to Month 12 ]
   general evaluation based on the Investigator judgment and local evaluation of the administration site
7. Safety primary outcome (Clinical evaluation - part I) [ Time Frame: From Day 0 to Month 12 ]
   Complete blood count
8. Safety primary outcome (Clinical evaluation - part II) [ Time Frame: From Day 0 to Month 12 ]
   Comprehensive Metabolic Panel

Secondary Outcome Measures :

1. Humoral Immunogenicity [ Time Frame: From Day 0 to Month 12 ]
   • Human cytomegalovirus (HCMV) gB immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA)
   • HCMV neutralization on MRC-5 cells
   • HCMV neutralization on ARPE-19 cells (depending on neutralization assay results in MRC-5 cells)
   • Lymphocytic choriomeningitis virus (LCMV) neutralization on ARPE-19 cells
2. Cellular Immunogenicity [ Time Frame: From Day 0 to Month 12 ]
   • LCMV NP-specific interferon γ (IFN-γ) Enzyme-Linked Immunospot Assay (ELISPOT)
   • LCMV NP-specific intracellular cytokine staining (ICS) of CD4+ and CD8+ T cells for IFN-γ, IL-2, TNF-α, CD107a and CD40L
   • HCMV pp65-specific IFN-γ ELISPOT
   • HCMV gB-specific IFN-γ ELISPOT
   • HCMV pp65-specific ICS of CD4+ and CD8+ T cells for IFN-γ, IL-2, TNF-α, CD107a and CD40L
   • HCMV gB-specific ICS of CD4+ and CD8+ T cells for IFN-γ, IL-2, TNF-α, CD107a and CD40L

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Signed informed consent
• Male or female, aged 18-45 years, in good health.
• Negative for HCMV
• Body mass index between 19 and 32 kg/m²
• Willing to forego receipt of other routine vaccinations (with the exception of seasonal influenza vaccination) for five months after study entry.
• For female volunteers: use of effective birth control for at least 2 months prior to study entry and willing to use effective birth control measures up to the Month 12 visit
• Comply with the requirements of this protocol (e.g. return for follow-up visits), as judged by the Investigator.

Exclusion Criteria:

• Works as a childcare provider.
• Pregnant or breastfeeding woman.
• Any screening safety laboratory value that is 2 times above the upper limit of normal value.
• Any confirmed or suspected immunodeficiency or autoimmune disorder.
• Treatment with any chronic immunosuppressive medication or other immuno-modifying drugs within 6 months prior to study entry. However, inhaled and topical steroids are allowed.
• Any vaccination other than for seasonal influenza within 3 months prior to study entry.
• Previous vaccination with an investigational HCMV vaccine.
• Receipt of blood, blood products and/or immunoglobulins within 3 months prior to study entry.
• History of severe allergic reactions and /or anaphylaxis
• Allergy to any component of the vaccine preparation.
• Expected to be unavailable to complete study follow up.
• Tested positive for HIV, HBsAg and/or anti-HCV.
• Participating in another clinical trial.
• Subject with a rash, dermatological condition or tattoos in the area of the injection site, as these may interfere with administration site reaction rating.

Contacts and Locations

Locations

Belgium

Center for Vaccinology Ghent

Ghent, East Flanders, Belgium, 9000

Sponsors and Collaborators

Hookipa Biotech

Centre for Vaccinology Ghent - CEVAC

Investigators

• Principal Investigator: Geert Leroux-Roels, MD PhD Prof; UZ Gent

More Information

• Responsible Party: Hookipa Biotech
• ClinicalTrials.gov Identifier: NCT02798692 History of Changes
• Other Study ID Numbers: H-100-001
• First Posted: June 14, 2016
• Last Update Posted: April 3, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Hookipa Biotech:

Prevention

Additional relevant MeSH terms:

Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs