Trial to Evaluate Safety and Immunogenicity of a Vaccine Against HCMV

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Placebo-controlled, Double-blind Phase I Dose-escalating Trial to Evaluate the Safety and Immunogenicity of a Vaccine Against Human Cytomegalovirus

Conditions
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Cytomegalovirus Infection

Intervention / Treatment
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* Biological: Low dose HB-101
* Biological: Medium dose HB-101
* Biological: High dose HB-101
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety primary outcome (local solicited symptoms) | 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 | Day 0 to Day 7 after each administration | 
| Safety primary outcome (general solicited symptoms) | 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. | Day 0 to Day 7 after each administration | 
| Safety primary outcome (Unsolicited AE´s) | Unsolicited AEs will be recorded through open-ended general inquiries | From Day 0 to Month 4 | 
| Safety primary outcome (SAEs and pregnancies) | SAEs and pregnancies will be recorded during the whole study | From Day 0 to Month 12 | 
| Safety primary outcome (Vital signs) | Vital signs (blood pressure, heart rate and body temperature) | From Day 0 to Month 12 | 
| Safety primary outcome (physical examination) | general evaluation based on the Investigator judgment and local evaluation of the administration site | From Day 0 to Month 12 | 
| Safety primary outcome (Clinical evaluation - part I) | Complete blood count | From Day 0 to Month 12 | 
| Safety primary outcome (Clinical evaluation - part II) | Comprehensive Metabolic Panel | From Day 0 to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immunogenicity | 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 | From Day 0 to Month 12 | 
| Cellular Immunogenicity | 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 | From Day 0 to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention