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

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicentre, Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in the SARS-CoV-2 Pandemic by Modulating the Immune System

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.

Study Overview

• Status: Completed
• Conditions: Infection, Respiratory Tract
• Intervention / Treatment: Biological: VPM1002; Biological: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 2038
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10787
    • Klinische Forschung Berlin GbR
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg GmbH
  • Baden-Württemberg
    • Stuttgart, Baden-Württemberg, Germany, 70178
      • Hautarztpraxis Dres. Leitz & Kollegen
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03050
      • MECS Cottbus GmbH
  • Hessen
    • Frankfurt, Hessen, Germany, 60389
      • Studienzentrum Dr. Keller
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Klinische Forschung Hannover Mitte GmbH
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Nordrhein-Westfalen
    • Essen, Nordrhein-Westfalen, Germany, 45355
      • Medizentrum Essen Borbeck
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55128
      • BAG Dres. med. Quist PartG
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • SIBAmed GmbH & Co. KG
  • Thüringen
    • Erfurt, Thüringen, Germany, 99084
      • SocraTec R&D GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VPM1002; The 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.	Biological: VPM1002; The investigational product will be administered via intradermal injection with a 1.0-ml syringe, sub-graduated into hundredths of ml (1/100 ml), and fitted with a short bevel needle (25G/0.50 mm or 26G/0.45 mm, 10 mm in length).
Placebo Comparator: Placebo; Physiological saline 0.1ml	Biological: Placebo; The investigational product will be administered via intradermal injection with a 1.0-ml syringe, sub-graduated into hundredths of ml (1/100 ml), and fitted with a short bevel needle (25G/0.50 mm or 26G/0.45 mm, 10 mm in length).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of days with severe respiratory disease at hospital and/or at home	From day 0 to day 240

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of hospital admissions	From day 0 to day 240
Cumulative incidence of documented SARS-CoV-2 infection	From day 0 to day 240
Number of days with self-reported fever (≥ 38 ºC)	From day 0 to day 240
Number of days with self-reported acute respiratory symptoms	From day 0 to day 240
Cumulative incidence of self-reported acute respiratory symptoms	From day 0 to day 240
Cumulative incidence of death for any reason	From day 0 to day 240
Cumulative incidence of death due to documented SARS-CoV-2 infection	From day 0 to day 240
Cumulative incidence of ICU admission for any reason	From day 0 to day 240
Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection	From day 0 to day 240
Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection	From day 0 to day 240

Collaborators and Investigators

• Sponsor: Vakzine Projekt Management GmbH
• Collaborators: FGK Clinical Research GmbH
• Investigators: Study Director: Leander Grode, Dr. rer. nat., Vakzine Projekt Management GmbH

Publications and helpful links

General Publications

• Blossey AM, Brückner S, May M, Parzmair GP, Sharma H, Shaligram U, Grode L, Kaufmann SHE, Netea MG, Schindler C. VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including COVID-19 in the Elderly: a phase III randomised, double-blind, placebo-controlled, multicenter clinical study. Clin Infect Dis. 2022 Nov 11. pii: ciac881. doi: 10.1093/cid/ciac881. [Epub ahead of print]

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): October 12, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: June 16, 2020
• First Submitted That Met QC Criteria: June 16, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: infectious respiratory diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections
• Other Study ID Numbers: VPM1002-DE-3.07CoV; 2020-001675-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is uncertainty whether the European Union General Data Protection Regulation allows dissemination of individual participant data to other researchers. Some reasons why the EU Regulation would not allow this are the lack of suitable safeguards when personal data are transferred to any researcher asking for it and the impairment of the rights of the subjects for erasure of their data once they are disseminated.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No