A Study to Assess Safety, Tolerability and Immunogenicity of the Live Attenuated hRSV Vaccine rBCG-N-hRSV
Condition: Respiratory Syncytial Virus Infections
MeSH terms: Respiratory Syncytial Virus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Human respiratory syncytial virus (hRSV) is the main cause of lower respiratory tract
      infection in children under one year of age. This study will evaluate the safety,
      tolerability and immunogenicity of a recombinant Mycobacterium bovis BCG vaccine that
      expresses the human Respiratory Syncytial Virus Nucleoprotein (N), in adult males (18 to 50
      years of age).
    

Detailed description: 
      hRSV is the main cause of infections in the lower respiratory tract, causing pneumonia,
      bronchiolitis and alveolitis in children younger than two years old. The infection is
      associated with the development of recurrent obstructive episodes in children with genetic
      predisposition. These hRSV infections also cause a high number of hospitalizations during the
      winter season.

      At Pontificia Universidad Católica de Chile, a vaccine has been developed to prevent hRSV
      infection, which is the conventional Bacillus Calmette Guerin (BCG) vaccine modified to
      recombinantly express the Nucleoprotein of hRSV (rBCG-N-hRSV). This vaccine has proven to be
      safe and immunogenic in different animal models, both in Chile and the USA. Doses of this
      vaccine have been manufactured under Current Good Manufacturing Practices (cGMP) conditions
      in USA, which are suitable to be tested in humans. Due to the unique immunogenic and safety
      characteristics observed in animal models used to test the efficacy of the rBCG-N-hRSV
      vaccine prototype, this clinical study will evaluate safety, tolerability and immunogenicity
      of the immunogenic cGMP formulation in healthy adults.

      Main objective: To characterize the safety and tolerability of escalating doses of the
      rBCG-N-hRSV vaccine, including doses of 5x10^3, 5x10^4 and 1x10^5 CFU (1%, 10% and 100% of
      the total dose) in healthy adult males of 18 to 50 years of age.

      Secondary objectives:

        1. To characterize the immune response against the Nucleoprotein of the hRSV in the
           previously stated escalating doses in the rBCG-N-hRSV.

        2. To characterize the immune response against the Mycobacterium in the previously stated
           escalating doses in the rBCG-N-hRSV.

      Study design: It corresponds to a phase I study, double blind (participant and personnel of
      the study) for the immunization of the tested vaccine or the control vaccine (Conventional
      BCG) within each cohort, to be performed in healthy adult males of 18 to 50 years of age.

      After a full clinical and laboratory evaluation to discard diseases, immunodeficiencies and
      latent tuberculosis infection, the participants will be enrolled into three cohorts in a open
      and successive manner. Within each cohort, they will be randomly and in a blind-manner
      assigned to receive the tested vaccine (rBCG-N-hRSV) or the control vaccine (conventional
      BCG).

      Cohort A: 6 participants vaccinated with 5x10^3 CFU of the rBCG-N-hRSV (1/100 part of the
      full dose) and 2 participants vaccinated with the conventional BCG (full dose).

      Cohort B: 6 participants vaccinated with 5x10^4 CFU of the rBCG-N-hRSV (1/10 part of the full
      dose) and 2 participants vaccinated with the conventional BCG (full dose).

      Cohort C: 6 participants vaccinated with 1x10^5 CFU of the rBCG-N-hRSV (full dose) and 2
      participants vaccinated with the conventional BCG (full dose).

      Each cohort will be completed within two weeks, followed by a period of 4 weeks of follow-up,
      in which the security data will be evaluated by a Data and Safety Monitoring Board (DSMB),
      who will determinate whether, according to the previously defined parameters, the escalation
      to the next cohort is possible, the cohort must be repeated, or whether the study must be
      stopped.

      The DSMB is constituted by 5 physician experts in microbiology, virology/vaccinology and
      tuberculosis, with a wide national recognition, affiliated to institutions different from the
      sponsoring institution.

      Number of participants: A minimum of 24 subjects, 8 by cohort. 18 participants will receive
      the tested vaccine and 6 will receive the control vaccine.

      Main variables: Safety and tolerability.

        -  Evaluation of reactogenicity (Local and systemic Adverse Events-AE)

        -  Evaluation of laboratory AE

        -  Serious AE

        -  Evaluation of the presence of the vaccine in body fluids

      Secondary variables: Immunogenicity

        -  Evaluation of the immune response against M. bovis BCG.

        -  Evaluation of the immune response against hRSV-N.
    

Intervention name(s): rBCG-N-hRSV 1/100; rBCG-N-hRSV 1/10; rBCG-N-hRSV full dose; Conventional BCG full dose
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): 5x10^3 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.; 5x10^4 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.; 1x10^5 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.; 2x10^5 colony forming units (CFU) of conventional BCG will be administered as an intradermal injection.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: human Respiratory Syncytial Virus; Phase I; Recombinant BCG vaccine