Phase 1 Study to Evaluate the Safety and Immunogenicity of a Candidate Vaccine Against Respiratory Syncytial Virus
Condition: Acute Bronchiolitis Due to Respiratory Syncytial Virus
MeSH terms: Bronchiolitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary and secondary objectives of this Phase 1 study are respectively to assess the
      safety and the immunogenicity of two administrations of the RSV vaccine candidate at three
      different doses.

      The study has a randomized, placebo-controlled, double-blind, sequential, parallel cohorts,
      dose-escalation (three dosages) design. Each of the three cohorts (N=20 subjects per cohort,
      total of 60 subjects) will receive placebo (n=5), or a low (15 µg, n=15), intermediate (50
      µg, n=15) or high dosage (150 µg, n=15) of candidate vaccine, on two occasions (Day 0 and Day
      56). Subjects will be healthy adult women aged between 18 and 45 years.

      There will be two phases: an active treatment phase from Day 0 to Month 3, and a follow-up
      phase from Month 3 + 1 day to Month 12.

      During the active phase, subjects will complete diary cards to record oral temperature
      (daily), solicited local and general adverse events (AEs) and unsolicited AEs for 7 days
      after each administration. Unsolicited AEs will be recorded up to Day 28 post-each
      administration. Serious adverse events (SAEs) and adverse events of specific interest (AESI)
      will be recorded throughout the duration of the active phase. Subjects will visit the
      clinical site for safety monitoring on Days 1, 7 and 28 following each administration.

      Blood will be drawn at a screening visit and the safety test data will be available just
      before 1st administration. The screening set includes markers of infection with hepatitis B
      virus, hepatitis C virus and human immunodeficiency virus. A serum sample will be taken for
      detection of pregnancy. At the next scheduled time points, pregnancy will be screened in a
      urine sample. Laboratory safety parameters will be examined further at Days 0, 1, 7, 28, 56,
      57, 63 and 84.

      During the follow-up phase, visits for safety monitoring are scheduled at Months 6, 9 and 12
      post-1st administration. SAEs and AESI will be recorded at each visit.

      Humoral immunity will be measured on Days 0, 28, 56, Month 3, Month 6, Month 9 and Month 12.
      Cellular immunity will be measured on Days 0, 7, 28, 56, 63 and 84.

      The duration of the study for each subject will be approximately 13 months. The total
      duration of the study will be approximately 18 months.
    

Detailed description: 
      Virometix designed and developed a candidate vaccine coded V-306 based on synthetic virus
      like particles (SVLP) that present the neutralizing Palivizumab epitope of the antigenic site
      II region of the F-protein (FsII). V-306 has been evaluated in cotton rats, mice and rabbits
      for safety and immunogenicity. Strong immunogenicity was demonstrated in mice and rabbits by
      ELISA and RSV A and B neutralization. Full protection with no vaccine-associated enhanced
      respiratory disease (VAERD) was demonstrated in a validated mouse challenge model. Reduction
      of the viral load with no VAERD was also shown in the cotton rat challenge model.

      The primary objective of the first-in-human Phase 1 study is to assess the safety of two
      administrations of the RSV vaccine candidate at three different dosages of V-306.

      The secondary objective is to assess the immunogenicity of two administrations of the RSV
      vaccine candidate at three different dosages of V-306.

      The study has a randomized, placebo-controlled, double-blind, sequential, parallel cohorts,
      dose-escalation (three dosages) design. It will be conducted in one centre. Each of the three
      cohorts (N=20 subjects per cohort, total of 60 subjects) will receive placebo (n=5), or a low
      (15 µg/administration, n=15), intermediate (50 µg/administration, n=15) or high dosage (150
      µg/administration, n=15) of candidate vaccine, on two occasions (Day 0 and Day 56). Subjects
      will be healthy adult women aged between 18 and 45 years. The enrolment schedule with
      sentinel dosing will be the same in each cohort. After each administration, the subject will
      be observed in the clinical trial centre for 120 minutes, before being discharged.

      The study will be in two phases: (1) an active treatment phase from Day 0 to Month 3, i.e.
      one month post 2nd administration, with unblinding and primary analysis of data collected up
      to Month 3, and (2) a follow-up phase from Month 3 + 1 day to Month 12 post-1st
      administration for safety and immunogenicity. The sponsor will be unblinded at Month 3, while
      the clinical site and laboratory will remain blinded during the whole study.

      During the active phase, subjects will complete diary cards to record oral temperature
      (daily), solicited local and general adverse events (AEs) and unsolicited AEs for 7 days
      after each administration. Unsolicited AEs will be recorded up to Day 28 post-each
      administration. Serious adverse events (SAEs) and adverse events of specific interest (AESI)
      will be recorded throughout the duration of the active phase. Subjects will visit the
      clinical site for safety monitoring on Days 1, 7 and 28 following each administration. A time
      window will be defined for each visit.

      Blood will be drawn at a screening visit (up to 14 days before Day 0 for lab safety analyses
      and up to 2 months before Day 0 for serology analyses) and the safety test data will be
      available just before 1st administration. The screening set includes markers of infection
      with hepatitis B virus, hepatitis C virus and human immunodeficiency virus. These data will
      be part of the baseline health status of each subject. A serum sample will be taken for
      detection of pregnancy. At the next scheduled time points, pregnancy will be screened in a
      urine sample and if positive will be confirmed by blood analysis. Laboratory safety
      parameters will be examined further at Days 0, 1, 7, 28, 56, 57, 63 and 84.

      During the follow-up phase, visits for safety monitoring are scheduled at Months 6, 9 and 12
      post-1st administration. SAEs and AESI will be recorded at each visit.

      Humoral immunity will be measured on Days 0, 28, 56, Month 3, Month 6, Month 9 and Month 12.
      Months 6, 9 and 12 aim to evaluate the persistence of the humoral response.

      Cellular immunity will be measured on Days 0, 7, 28, 56, 63 and 84. Data collection will use
      an electronic Case Report Form (eCRF). The duration of the study for each subject will be
      approximately 13 months. The total duration of the study will be approximately 18 months.
    

Intervention name(s): V-306 candidate vaccine
Intervention type(s): Biological
Intervention description(s): Each V-306 monomer consists of the following elements:
A Lipopeptide Building Block that contains an optimized, artificially designed coiled-coil domain, which self-assembles into highly stable trimers.
A 'universal' T-helper epitope fused at the C-terminus of the coiled-coil domain.
A lipid component di-palmitoyl-S-glyceryl cysteine (Pam2C), fused at the N-terminus.
A mimetic of the Palivizumab epitope, referred to RSV F-protein site II antigen mimetic (FsIIm), which is coupled near the C-terminus of the Lipopeptide Building Block via a short maleimide-PEG-oxime linker.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Randomized, placebo-controlled, double-blind, sequential, parallel cohorts, dose-escalation (three dosages) study in one centre.
Masking: Double (Participant, Investigator)
Primary purpose: Prevention