A Study to Assess Safety, Tolerability and Immunogenicity of the Live Attenuated hRSV Vaccine rBCG-N-hRSV

NCT03213405 | Completed Phase 1 Results DMC

• 2 other identifiers: 15-216rBCG-N-VRSh 001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Respiratory Syncytial Virus Infections

Keywords

human Respiratory Syncytial Virus; Phase I; Recombinant BCG vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Required Adverse Events Grade II, III, and IV, Laboratory Adverse Events Grade II, III, and IV, and Severe Considered Adverse Events Related to the Vaccine.

  To determine the safety of the rBCG-N-hRSV by evaluating the number of vaccinated participants with adverse events (AEs) due to the vaccination. Among these AEs, the following will be measured: Number of subjects with required AEs grade II, III, and IV, laboratory AEs grade II, III, and IV, and severe AEs (SAEs) considered related to the vaccine. Required AEs included pain, induration, pustule, fever, headache, myalgia, and diarrhea, among others. AEs were collected by self-report on diary cards, study visits, and study phone calls. Laboratory AEs included hematological and biochemical parameters, such as blood counts, transaminases, cholesterol, creatine phosphokinase, and urine analyses, among others. SAEs were defined as any untoward medical occurrence that resulted in death; was life-threatening; required hospitalization; or resulted in disability, among others. Grade 4 laboratory AEs were also considered SAEs.

  Up to 180 days post-vaccination (A total of 11 months and 6 days for the whole study)

Study Arms (4)

Conventional BCG full dose

ACTIVE COMPARATOR

Participants will receive one full dose of the Conventional BCG vaccine administered as an intradermal injection at study entry.

Biological: Conventional BCG full dose

rBCG-N-hRSV 1/100 dose

EXPERIMENTAL

Participants will receive one 1/100 dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.

Biological: rBCG-N-hRSV 1/100

rBCG-N-hRSV 1/10 dose

EXPERIMENTAL

Participants will receive one 1/10 dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.

Biological: rBCG-N-hRSV 1/10

rBCG-N-hRSV full dose

EXPERIMENTAL

Participants will receive one full dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.

Biological: rBCG-N-hRSV full dose

Interventions

rBCG-N-hRSV 1/100 BIOLOGICAL

5x10\^3 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.

rBCG-N-hRSV 1/100 dose

rBCG-N-hRSV 1/10 BIOLOGICAL

5x10\^4 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.

rBCG-N-hRSV 1/10 dose

rBCG-N-hRSV full dose BIOLOGICAL

1x10\^5 colony forming units (CFU) of rBCG-N-hRSV will be administered as an intradermal injection.

rBCG-N-hRSV full dose

Conventional BCG full dose BIOLOGICAL

2x10\^5 colony forming units (CFU) of conventional BCG will be administered as an intradermal injection.

Conventional BCG full dose

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Chilean male within 18 and 50 years old.
• To have accepted his voluntary participation through the sign of the informed consent.
• To be in good health, according to the medical history, physical examination and normal laboratory tests.
• To be vaccinated with BCG once or twice during his life.

You may not qualify if:

• Symptoms or diagnosis suggesting some systemic disease including renal, liver, cardiovascular or pulmonary impairment, immunodeficiency, autoimmune disease, malignancies, psychiatric or other conditions that can interfere on the interpretation of the results or compromise the health of the participants.
• Body mass index lower than 19 and higher that 30 kg/m2 and/or weight under 50 kg.
• Not being able to attend all the study visits (face-to-face and call phones) or not follow the specified instructions (fasting, not doing intense physical exercise during the previous 24 hours to the visits and 72 hours post-vaccine).
• Signs of latent or active infectious diseases by Mycobacterium tuberculosis (TB): QuantiFERON-TB positive test or Chest X-ray suggesting Tuberculosis (TBC).
• Positive screening for Human Immunodeficiency Virus (HIV), Hepatitis B superficial antigen (HBsAG) and anti-Hepatitis C Virus (HCV).
• Evidence of primary or secondary immunodeficiency, determined by history, physical test and levels of serum immunoglobulins and lymphocytes sub-populations at the screening.
• Use of immunosuppressors during the last 6 months previous to the visit.
• Use of inhaled corticosteroids during the last year or with antecedents of bronchial hyper-reactivity.
• Antecedents of intradomiciliary contact with subjects with Tuberculosis or other mycobacteria, even when he/she is under treatment.
• Antecedents of substance abuse (drugs or alcohol), according to DSM IV (See footnote\*)
• Occurrence of any serious adverse event associated to the previous BCG vaccination.
• History of severe allergic reaction or anaphylaxis to vaccines
• History of severe infections (use of IV antibiotics, opportunist, latent TBC, herpes zoster) during six months previous to the visit.
• Not use or rejection to the use of contraceptives during the whole study (See footnote\*\*).
• Administration of Immunoglobulins or blood-derived products during the six months previous to the visit or the planning of its use during the study.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• Comisión Nacional de Investigación Científica y Tecnológica: collaborator
• Millennium Institute on Immunology and Immunotherapy: collaborator

Study Sites (1)

Pontificia Universidad Católica de Chile

Santiago, 8330091, Chile

Location

Related Publications (7)

• Bueno SM, Gonzalez PA, Cautivo KM, Mora JE, Leiva ED, Tobar HE, Fennelly GJ, Eugenin EA, Jacobs WR Jr, Riedel CA, Kalergis AM. Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20822-7. doi: 10.1073/pnas.0806244105. Epub 2008 Dec 15.

  PMID: 19075247 BACKGROUND

• Cautivo KM, Bueno SM, Cortes CM, Wozniak A, Riedel CA, Kalergis AM. Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells induced by recombinant bacillus Calmette-Guerin promotes virus clearance and protects from infection. J Immunol. 2010 Dec 15;185(12):7633-45. doi: 10.4049/jimmunol.0903452. Epub 2010 Nov 17.

  PMID: 21084664 BACKGROUND

• Cespedes PF, Bueno SM, Ramirez BA, Gomez RS, Riquelme SA, Palavecino CE, Mackern-Oberti JP, Mora JE, Depoil D, Sacristan C, Cammer M, Creneguy A, Nguyen TH, Riedel CA, Dustin ML, Kalergis AM. Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells. Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):E3214-23. doi: 10.1073/pnas.1400760111. Epub 2014 Jul 23.

  PMID: 25056968 BACKGROUND

• Palavecino CE, Cespedes PF, Gomez RS, Kalergis AM, Bueno SM. Immunization with a recombinant bacillus Calmette-Guerin strain confers protective Th1 immunity against the human metapneumovirus. J Immunol. 2014 Jan 1;192(1):214-23. doi: 10.4049/jimmunol.1300118. Epub 2013 Dec 6.

  PMID: 24319265 BACKGROUND

• Cespedes PF, Rey-Jurado E, Espinoza JA, Rivera CA, Canedo-Marroquin G, Bueno SM, Kalergis AM. A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice. Vaccine. 2017 Feb 1;35(5):757-766. doi: 10.1016/j.vaccine.2016.12.048. Epub 2017 Jan 5.

  PMID: 28065474 BACKGROUND

• Pacheco GA, Andrade CA, Galvez NMS, Vazquez Y, Rodriguez-Guilarte L, Abarca K, Gonzalez PA, Bueno SM, Kalergis AM. Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults. Front Immunol. 2023 Jul 18;14:1215893. doi: 10.3389/fimmu.2023.1215893. eCollection 2023.

  PMID: 37533867 DERIVED

• Abarca K, Rey-Jurado E, Munoz-Durango N, Vazquez Y, Soto JA, Galvez NMS, Valdes-Ferrada J, Iturriaga C, Urzua M, Borzutzky A, Cerda J, Villarroel L, Madrid V, Gonzalez PA, Gonzalez-Aramundiz JV, Bueno SM, Kalergis AM. Safety and immunogenicity evaluation of recombinant BCG vaccine against respiratory syncytial virus in a randomized, double-blind, placebo-controlled phase I clinical trial. EClinicalMedicine. 2020 Oct 6;27:100517. doi: 10.1016/j.eclinm.2020.100517. eCollection 2020 Oct.

  PMID: 33073219 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Dr. Alexis Kalergis
• Organization: Pontificia Universidad Católica de Chile

akalergis@bio.puc.cl

+56223541924

Study Officials

• Alexis M Kalergis, PhD

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

• Katia Abarca, MD

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 11, 2017
• Study Start: June 27, 2017
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: December 11, 2020
• Results First Posted: December 11, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CL (1)