Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects
Condition: Rabies; Rabies Immunisation
MeSH terms: Rabies
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-center, observer-blinded, dosage-escalation trial to evaluate the safety,
      tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT in
      rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49. There are
      4 dose groups: Group A will receive ChAd155-RG at the lower dosage (5x1010vp) on Day 1, then
      placebo injections on Days 8, 15, and 22; Group B will receive ChAd155-RG at the higher
      dosage (1x1011vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group C will
      receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and 15, and placebo injections
      on Days 8 and 22; Group D will receive RABAVERT at the standard dose (1 mL) on Days 1, 8, and
      22, and a placebo injection on Day 15. Since this is a dosage-escalation study, sentinel
      subjects will be used at each dosage level before non-sentinel subjects will be enrolled. The
      study will be conducted at Emory University Vaccine and Treatment Evaluation Unit (VTEU).
      This trial is expected to take approximately 48 months to complete. The duration of each
      subject's participation is approximately 13 months, from recruitment through the last study
      visit. The primary objectives of this study are: 1) Assessment of the safety, tolerability,
      and reactogenicity of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of
      ChAd155-RG at 1x1011vp per dose; 2) Comparison of the safety, tolerability, and
      reactogenicity of one or two doses of ChAd155-RG, with three doses of RABAVERT.
    

Detailed description: 
      This is a single-center, observer-blinded, Phase 1, dosage-escalation trial to evaluate the
      safety, tolerability, reactogenicity, and immunogenicity of ChAd155-RG compared with RABAVERT
      in rabies virus-naïve healthy male and non-pregnant female adult subjects ages 18-49.
      Subjects who have never received a licensed or investigational rabies virus vaccine, or an
      Ad-based investigational vaccine, and who have never been exposed to a rabid animal will be
      eligible for enrollment. There are 4 dose groups: Group A will receive ChAd155-RG at the
      lower dosage (5x1010vp) on Day 1, then placebo injections on Days 8, 15, and 22; Group B will
      receive ChAd155-RG at the higher dosage (1x1011vp) on Day 1, then placebo injections on Days
      8, 15, and 22; Group C will receive ChAd155-RG at the higher dosage (1x1011vp) on Days 1 and
      15, and placebo injections on Days 8 and 22; Group D will receive RABAVERT at the standard
      dose (1 mL) on Days 1, 8, and 22, and a placebo injection on Day 15. Since this is a
      dosage-escalation study, sentinel subjects will be used at each dosage level before
      non-sentinel subjects will be enrolled. The SMC will review the available safety,
      reactogenicity, AE, and lab data of all the sentinel subjects, and will decide if the
      remaining non-sentinel subjects should be enrolled. The study will be conducted at Emory
      University Vaccine and Treatment Evaluation Unit (VTEU). This trial is expected to take
      approximately 48 months to complete. The duration of each subject's participation is
      approximately 13 months, from recruitment through the last study visit. The primary
      objectives of this study are: 1) Assessment of the safety, tolerability, and reactogenicity
      of one dose of ChAd155-RG at 5x1010vp per dose, or one or two doses of ChAd155-RG at 1x1011vp
      per dose; 2) Comparison of the safety, tolerability, and reactogenicity of one or two doses
      of ChAd155-RG, with three doses of RABAVERT. The secondary objective is to assess the serum
      rabies VNA levels by a standard, WHO-approved, RFFIT, as assessed by immune response kinetics
      (through approximately 12 months after first dose of vaccine), seroconversion rates, and peak
      GMT in each treatment arm.
    

Intervention name(s): ChAd155-RG; Placebo; Rabies Vaccine
Intervention type(s): Biological; Other; Biological
Intervention description(s): The ChAd155-RG Vaccine consists of a replication-defective group C ChAd, ChAd155, expressing RG under the control of the CMV promoter. The RG sequence cloned into the ChAd155 vector is a medoid, a natural viral strain with the highest average percent of amino acid identity among all RG sequences annotated in the NCBI database. The selected RG (NCBI strain AGN94271) shares an average 94% percent identity to the RGs in current vaccines.; 0.9% Sodium Chloride, USP injection.; The RABAVERT Vaccine is an inactivated, purified chick embryo cell vaccine (PCECV). It consists of lyophilized rabies virus (strain Flury LEP) that has been propagated in chicken fibroblasts, inactivated with beta-propiolactone, and concentrated and purified by centrifugation
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Adults; ChAd155-RG; Dosage-Escalation; Healthy; Immunogenicity; RABAVERT; Rabies; Safety; Vaccine