Randomized, double-blind, phase 2 clinical trial controlled with conventional Bacillus Calmette-Guérin (BCG) vaccine to evaluate the safety and immunogenicity of a recombinant BCG vaccine that expresses the respiratory syncytial virus (RSV) nucleoprotein (N) (rBCG-N-RSV) in adults over 60 years of age.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biothervax SpA

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Decision date (initial)

2024-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Biothervax SpA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

To evaluate the safety of the rBCG-N-RSV vaccine compared to conventional BCG in adults older than 60 years.
To compare the cellular anti-mycobacterial immune response of both vaccines in adults older than 60 years.
To characterize the cellular immune response against RSV nucleoprotein (N) generated by the rBCG-N-RSV vaccine in adults older than 60 years as compared to the response induced by the conventional BCG.

Secondary objectives 4

1. To compare the anti-mycobacterial humoral immune response of both rBCG-N-RSV and conventional BCG vaccines in adults older than 60 years.
2. To characterize the RSV anti-nucleoprotein humoral immune response generated by the rBCG-N-RSV vaccine as compared to the response induced by the conventional BCG in adults older than 60 years.
3. Exploratory: To quantify the incidence of symptomatic RSV infection in subjects who received rBCG-N RSV vaccine and compare it with the group receiving conventional BCG within 6 months of vaccination.
4. Exploratory: To detect, in peripheral blood, mononuclear cells of specific CD4+ and CD8+ T cells that express activation induced markers (AIM) and memory markers in a subgroup of participants that receive the control and the study vaccine.

Conditions and MedDRA coding

The present Phase 2 clinical study will evaluate the safety and immunogenicity of the immunogenic formulation cGMP rBCG-N-RSV of 100,000 CFU in adults over 60 years of age.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Has completed the written informed consent process
2. 2. Males or females, over 60 years of age as of the date of signature of the informed consent form
3. 3. Has a stable state of health or controlled (health parameters within the normal range for their disease) chronic diseases that do not fall within the exclusion criteria
4. 4. Willingness to comply with study procedures.
5. 5. No plans to move to another city in the next 6 months and willing to be contacted by the research team within the study period.
6. 6. Not participate in another research study in the previous 3 months, nor plans to participate in another research study in the next 6 months
7. 7. Agrees to avoid elective surgery during the study
8. 8. Willingness to receive HIV test results.
9. 9. Not having received a BCG vaccination within the last 10 years before study vaccination.

Exclusion criteria 33

1. 1. Oral temperature ≥37.5°C, axillary ≥37.5°C or tympanic temperature ≥38.0°C in the last 24 hours
2. 10. Previous medical history that may compromise the safety of the study participant, including but not limited to significant impairment of lung function (such as pulmonary diffusion of carbon dioxide <80% or FEV1 ≤80%) due to tuberculosis infection or other pulmonary disease; chronic heart disease with signs of heart failure (NYHA Class II Heart Failure or more) or coronary heart disease, suspicion of progressive neurological disease; uncontrolled epilepsy, liver disease.
3. 11. Administration of attenuated vaccines within 30 days before the start of the study or 14 days for inactivated ones.
4. 12.Having received transfusions or blood products within the 6 months before the start of the study.
5. 13.Uncontrolled hypertension or systolic blood pressure greater than 160 mmHg at the beginning of the study or diastolic greater than 90 mmHg.
6. 14.Active neoplasia
7. 15.Stage 2 or higher chronic obstructive pulmonary disease.
8. 16.Chronic bronchial asthma with systemic corticosteroids, or with a history of having presented crises that have led to an emergency consultation within the last 2 months.
9. 17.Renal disease with estimated or relative creatinine clearance ≤ 70 ml/min x 1.73 m2.
10. 18.Evidence of a new acute illness that may compromise the safety of the study participant, such as fever (oral or axillary temperature greater than or equal to 37.5°C) or suspicion of active infection.
11. 19.History or laboratory evidence of chronic viral hepatitis.
12. 2. Weight less than 50 kg, as well as BMI less than 18.5 or greater than 35 kg/m2
13. 20.History of alcohol or drug abuse in the last 2 years.
14. 21. Smoking more than 30 cigarettes a day, or cannabis use three or more days a week.
15. 22.History of keloid formation.
16. 23.Congenital diseases of importance, such that they weaken the basal condition of the volunteer.
17. 24.Congenital or acquired absence of the spleen.
18. 25.Coagulation disorders or known thrombocytopenia of less than 100,000 platelets/mm3.
19. 26.Having undergone chemotherapy treatment in the last 6 months.
20. 27.Generalized urticaria in the last 2 months.
21. 28.History of hereditary or acquired angioneurotic edema.
22. 29.Any previous medical condition that the investigator considers may compromise the safety of the subject in the study.
23. 3. History of treatment or current history of active or latent tuberculosis infection.
24. 30.Not being available for all study visits (both face-to-face and by telephone) and specific instructions as appropriate (fasting, abstaining from intense physical exercise during the 24 hours before the study visits and during the 72 hours after vaccination).
25. 4. History of unprotected occupational exposure to an individual with active tuberculosis in a healthcare setting within the past 6 months.
26. 5. Immunosuppressive drugs used within the previous 42 days (inhaled and topical corticosteroids are allowed).
27. 6. Received documented investigational tuberculosis vaccine at any time.
28. 7. Unstable hormonal status, i.e. subjects with any change (dose, formulation, or route) in hormone replacement therapies (including levothyroxine, insulin, estrogen, progesterone etc.) in the last 12 weeks.
29. 8. History or laboratory evidence of any possible past, present, or future immunodeficiency status, including, but not limited to, any laboratory indication of HIV-1 infection.
30. 9. Allergy to BCG vaccine or its components, as well as the existence of contraindications for BCG administration as described in the BCG prescribing information.
31. 31. Pregnant women or women of childbearing potential (WOCBP) who are unable or unwilling to utilize appropriate methods of contraception during the study.
32. 32. Breast-feeding women
33. 33. Male with heterosexual sexual activity with women of childbearing potential (WOCBP) who do not agree to use adequate contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Occurrence, intensity, and duration of the local solicited AEs (evolution of the "flare-up") until the generation of the scar.
2. Occurrence, intensity and duration of unsolicited AEs during the 6-month follow-up.
3. Occurrence of AEs during the 6-month follow-up duration.
4. Alterations to the hemogram and/or biochemical profile at 30- and 180- days post vaccination compared to pre-vaccination profile.
5. Production of IFN-γ and IL-2 by T cells upon exposure to purified protein derivative (PPD) mycobacterial antigen 7 days prior vaccination and 30- and 180-days post vaccination.
6. Production of IFN-γ and IL-2 by T cells upon exposure to recombinant RSV nucleoprotein antigen 7 days prior vaccination and 30- and 180-days post vaccination.

Secondary endpoints 2

1. Presence and titers of serum IgG antibodies against Purified Protein Derived Mycobacterial antigen (PPD) via ELISA.
2. Presence and titers of serum IgG against RSV nucleoprotein via ELISA.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biothervax SpA

Sponsor organisation

Biothervax SpA

Address

Siena 2457

City

Las Condes

Postcode

7610671

Country

Chile

Scientific contact point

Organisation

Biothervax SpA

Contact name

Sponsor’s Representative

Public contact point

Organisation

Biothervax SpA

Contact name

Sponsor’s Representative

Third parties 3

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications