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Study to Assess VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in COVID-19 Pandemic

Phase 3
Completed
Conditions
Infection, Respiratory Tract
Interventions
Biological: VPM1002
Biological: Placebo
Registration Number
NCT04435379
Lead Sponsor
Vakzine Projekt Management GmbH
Brief Summary

The aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic .

VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine.

VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2.

Detailed Description

Based on the evidence that BCG \[Bacille Calmette-Guérin\] vaccine

1. can potentiate immune responses to other vaccines through induction of trained innate immunity and heterologous adaptive immunity, and

2. can reduce the incidence of respiratory infections, exert antiviral effects in experimental models, and reduce viremia in an experimental human model of viral infection, it is hypothesized that BCG vaccination may induce (partial) protection against the susceptibility to and/or severity of SARS-CoV-2 infections.

VPM1002 is being developed with the aim to replace BCG by a vaccine that has a better safety profile and superior efficacy. Evidence from pre-clinical and clinical studies demonstrate that VPM1002 is safer and is more immunogenic than the existing BCG vaccine (for more information, please revert to the IB). It is therefore anticipated that VPM1002 will also perform better in reducing the severity of the symptoms of an infection with the SARS-CoV-2 than the BCG vaccine. Further, manufacturing of VPM1002 using state-of-the-art production methods will help hasten the production of millions of doses in a very short time and thus would be beneficial in the current SARS-CoV-2 pandemic situation.

The current trial will assess the efficacy and safety of VPM1002 to reduce the hospital admissions and clinical consequences of SARS-CoV-2 infections in the elderly population in the SARS-CoV-2 pandemic by modulating the immune system.

A total of 2038 adults aged 60 or above will be enrolled across involved clinical trial sites in Germany. Informed consent will be obtained from the subjects willing to take part in the trial. This will be followed by assessment of the eligibility criteria. Subjects who fulfil the inclusion/exclusion criteria will be centrally randomized in a 1:1 ratio to receive a single dose (0.1 ml) of either VPM1002 or Placebo.

All subjects will be requested to sign into a web-based tool designed for this trial. Every subject is encouraged to name a designated caregiver who may provide follow-up data in case of hospitalisation or severe illness of the study subject. All subjects will be followed-up entirely remotely. The questionnaires will be designed to collect data regarding hospitalisation, adverse events (AE)/serious adverse events (SAE), ICU admissions and other secondary endpoints. The investigators will review the outcome and safety data.

The duration of follow-up will be 240 days. Subjects with confirmed SARS-CoV-2 infection (with or without symptoms) will be followed for at least 6 weeks (from the date of test result), independent of the total trial duration.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2038
Inclusion Criteria
  1. Male or female adult (≥ 60 years)
  2. Subject is contractually capable, able to understand information on study and has signed informed consent sheet
  3. Subject has access to an internet-enabled electronic device
Exclusion Criteria
  1. Known active or latent Mycobacterium tuberculosis infection

  2. Fever (> 38 °C) or respiratory tract infection within the past 24 hours

  3. Current active viral or bacterial infection

  4. Expected vaccination during the study period; vaccinations against influenza and pneumococcal disease are allowed with ≥ 4 weeks between these vaccinations and the trial vaccination

  5. Participation in another interventional study within 30 days before screening and during this study

  6. Known hypersensitivity or allergy to (components of) the VPM1002 vaccine or serious adverse reactions to prior Bacille Calmette-Guérin (BCG) administration

  7. Severely immunocompromised subjects, including:

    1. subjects with known infection by the human immunodeficiency virus (HIV-1);
    2. subjects with solid organ transplantation;
    3. subjects with bone marrow transplantation;
    4. subjects under chemotherapy, immunotherapy, or radiotherapy;
    5. subjects with primary immunodeficiency;
    6. treatment with any anti-cytokine therapies;
    7. treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months, or likely use of oral or intravenous steroids in the next 4 weeks;
  8. History of malignancies, unless the subject has been free of the disease for ≥ 2 years; exception: subjects with adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer and adequately treated carcinoma in situ of the cervix may participate in the trial

  9. Previous positive SARS-CoV-2 test result

  10. Person is an employee of the sponsor, a relative of the sponsor or investigator, or is employed in the same department as the investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
VPM1002VPM1002The active ingredient of the recombinant BCG vaccine, VPM1002, is Mycobacterium bovis rBCGΔureC::hly, freeze-dried and standardized to the number of viable mycobacteria (colony forming units; CFU) per application. Dose: 2-8 x 10e5 CFU VPM1002 administered in 0.1 ml reconstituted suspension.
PlaceboPlaceboPhysiological saline 0.1ml
Primary Outcome Measures
NameTimeMethod
Number of days with severe respiratory disease at hospital and/or at homeFrom day 0 to day 240
Secondary Outcome Measures
NameTimeMethod
Cumulative incidence of death due to documented SARS-CoV-2 infectionFrom day 0 to day 240
Cumulative incidence of self-reported acute respiratory symptomsFrom day 0 to day 240
Cumulative incidence of ICU admission due to documented SARS-CoV-2 infectionFrom day 0 to day 240
Cumulative incidence of death for any reasonFrom day 0 to day 240
Cumulative incidence of hospital admission due to documented SARSCoV- 2 infectionFrom day 0 to day 240
Cumulative incidence of hospital admissionsFrom day 0 to day 240
Cumulative incidence of documented SARS-CoV-2 infectionFrom day 0 to day 240
Number of days with self-reported fever (≥ 38 ºC)From day 0 to day 240
Cumulative incidence of ICU admission for any reasonFrom day 0 to day 240
Number of days with self-reported acute respiratory symptomsFrom day 0 to day 240

Trial Locations

Locations (12)

Klinische Forschung Hannover Mitte GmbH

🇩🇪

Hannover, Niedersachsen, Germany

Medizinische Hochschule Hannover

🇩🇪

Hannover, Niedersachsen, Germany

SocraTec R&D GmbH

🇩🇪

Erfurt, Thüringen, Germany

Studienzentrum Dr. Keller

🇩🇪

Frankfurt, Hessen, Germany

Medizentrum Essen Borbeck

🇩🇪

Essen, Nordrhein-Westfalen, Germany

Klinische Forschung Berlin GbR

🇩🇪

Berlin, Germany

BAG Dres. med. Quist PartG

🇩🇪

Mainz, Rheinland-Pfalz, Germany

emovis GmbH

🇩🇪

Berlin, Germany

SIBAmed GmbH & Co. KG

🇩🇪

Leipzig, Sachsen, Germany

MECS Cottbus GmbH

🇩🇪

Cottbus, Brandenburg, Germany

Hautarztpraxis Dres. Leitz & Kollegen

🇩🇪

Stuttgart, Baden-Württemberg, Germany

Klinische Forschung Hamburg GmbH

🇩🇪

Hamburg, Germany

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