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Respiratory Syncytial Virus InfectionsPhase 1EVA-VRS01NCT03213405

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

A Phase 1 study testing rBCG-N-hRSV 1/100, rBCG-N-hRSV 1/10 and rBCG-N-hRSV full dose in people with Respiratory Syncytial Virus Infections, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 50 years, men onlyHealthy volunteers can take part
Conditions the study is for
Respiratory Syncytial Virus Infections
What is being tested?
rBCG-N-hRSV 1/100, rBCG-N-hRSV 1/10 and rBCG-N-hRSV full dose
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteChile
Study dates
27 Jun 2017to 1 Jun 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Eczema at the vaccination site (deltoid zone).
  • Antecedents of keloid scar.
  • Being vaccinated with BCG during the last 10 years.
  • History of being vaccinated with BCG three or more times or the presence of three BCG scars.
  • Using other investigational products during the 30 days previous to the study.
  • Administration of any vaccine during the 8 weeks previous to the recruitment.
  • Planned administration of any other different vaccine 30 days after the vaccination with the rBCG-N-hRSV.
  • Acute illness symptoms and/or feverish symptoms at the time or during the last seven days previous to the recruitment (fever defined as an oral or axillary temperature of >38ºC).
  • () Substance abuse (drugs or alcohol): Maladaptive pattern of substance abuse that leads to a deterioration or clinical significant discomfort, expressed by one or more associated problems, during a time of twelve months, in one of the four vitals areas: inability to achieve main obligations; consume in dangerous situations, such as driving a vehicle; legal problems; consume despite the social and interpersonal difficulties associated.
  • () Given the remote possibility of negative effects produced by the vaccination in the sperm, the recruitment will be performed only to volunteers that are not planning of conceiving a child during the study duration. In each visit, the abstinence fulfillment will be checked or the use of effective contraceptive.
  • Eligibility criteria:
  • The eligibility of the volunteers will be performed if they fulfill the inclusion criteria and fulfill none of the mentioned exclusion criteria, also presenting all the normal screening study.
  • All the volunteers must sign the Informed consent approved by the Ethic Committee of the "Facultad de Medicina" of the "Pontificia Universidad Católica de Chile", before starting the first screening visit.

Trial locations and contacts

1 site in 1 country.

Chile1 site

  • Pontificia Universidad Católica de Chile

    Santiago, 8330091

Other trials in Chile

About this study

Official title: A Double Blind, Controlled by Conventional BCG, Dose-escalation Phase I Study, to Evaluate Safety, Tolerability and Immunogenicity of a Mycobacterium Bovis BCG (Bacillus Calmette-Guérin) Vaccine, 1331 Danish Strain, Live Attenuated and Recombinant for the Expression of Human Respiratory Syncytial Virus Nucleoprotein (N) in Healthy Males Within 18 and 50 Years of Age

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).

Read the 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.
Being tested
rBCG-N-hRSV 1/100, rBCG-N-hRSV 1/10, rBCG-N-hRSV full dose, Conventional BCG full dose
Keywords
human Respiratory Syncytial Virus, Phase I, Recombinant BCG vaccine
Medical subject headings
Respiratory Syncytial Virus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rBCG-N-hRSV 1/100Biological

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

  • rBCG-N-hRSV 1/10Biological

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

  • rBCG-N-hRSV full doseBiological

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

  • Conventional BCG full doseBiological

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

Study groups in NCT03213405
Study groupRoleWhat they receive
Conventional BCG full doseActive comparatorParticipants will receive one full dose of the Conventional BCG vaccine administered as an intradermal injection at study entry.
Receives: Biological: Conventional BCG full dose
rBCG-N-hRSV 1/100 doseExperimentalParticipants will receive one 1/100 dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.
Receives: Biological: rBCG-N-hRSV 1/100
rBCG-N-hRSV 1/10 doseExperimentalParticipants will receive one 1/10 dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.
Receives: Biological: rBCG-N-hRSV 1/10
rBCG-N-hRSV full doseExperimentalParticipants will receive one full dose of the rBCG-N-hRSV vaccine administered as an intradermal injection at study entry.
Receives: Biological: rBCG-N-hRSV full dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2017
  2. Study start27 Jun 2017
  3. Primary completion1 Jun 2018
  4. Study completion1 Jun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03213405
Sponsor's protocol ID
15-216
Other IDs
rBCG-N-VRSh 001
Acronym
EVA-VRS01
Status last verified
Nov 2020
First submitted
30 Jun 2017
Last updated
11 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 19075247

  • 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.

    PubMed 21084664

  • 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.

    PubMed 25056968

  • 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.

    PubMed 24319265

  • 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.

    PubMed 28065474

  • 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.

    PubMed 37533867

  • 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.

    PubMed 33073219

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rBCG-N-hRSV 1/100, rBCG-N-hRSV 1/10 and rBCG-N-hRSV full dose in people with Respiratory Syncytial Virus Infections, run by Pontificia Universidad Catolica de Chile at 1 site in Chile.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Up to 180 days post-vaccination (A total of 11 months and 6 days for the whole study)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03213405, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2020.

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