Trial to Evaluate Safety and Immunogenicity of a Vaccine Against HCMV

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

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Biological: Low dose HB-101; Biological: Medium dose HB-101; Biological: High dose HB-101; Biological: Placebo

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • East Flanders
    • Ghent, East Flanders, Belgium, 9000
      • Center for Vaccinology Ghent

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hookipa Biotech GmbH
• Collaborators: Centre for Vaccinology Ghent - CEVAC
• Investigators: Principal Investigator: Geert Leroux-Roels, MD PhD Prof, UZ Gent

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): April 3, 2018
• Last Update Submitted That Met QC Criteria: April 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Prevention
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections
• Other Study ID Numbers: H-100-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO