Cytomegalovirus Infection
Conditions
Keywords
Prevention
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.
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.
Interventions
BIOLOGICALLow dose HB-101
Three intra muscular administrations at Day 0, Month 1 and Month 3
BIOLOGICALMedium dose HB-101
Three intra muscular administrations at Day 0, Month 1 and Month 3
BIOLOGICALHigh dose HB-101
Three intra muscular administrations at Day 0, Month 1 and Month 3
BIOLOGICALPlacebo
Three intra muscular administrations at Day 0, Month 1 and Month 3. The diluent is used as placebo.
Sponsors
Centre for Vaccinology Ghent - CEVAC
Hookipa Biotech GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety primary outcome (Clinical evaluation - part II) | From Day 0 to Month 12 | Comprehensive Metabolic Panel |
| Safety primary outcome (physical examination) | From Day 0 to Month 12 | general evaluation based on the Investigator judgment and local evaluation of the administration site |
| Safety primary outcome (Clinical evaluation - part I) | From Day 0 to Month 12 | Complete blood count |
| Safety primary outcome (local solicited symptoms) | 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 |
| Safety primary outcome (general solicited symptoms) | 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. |
| Safety primary outcome (Unsolicited AE´s) | From Day 0 to Month 4 | Unsolicited AEs will be recorded through open-ended general inquiries |
| Safety primary outcome (SAEs and pregnancies) | From Day 0 to Month 12 | SAEs and pregnancies will be recorded during the whole study |
| Safety primary outcome (Vital signs) | From Day 0 to Month 12 | Vital signs (blood pressure, heart rate and body temperature) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cellular Immunogenicity | 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 |
| Humoral Immunogenicity | 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 |
Countries
Belgium
Outcome results
None listed