## Protocol Section
### Identification Module
**NCT ID:** NCT04435379

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

**Official Title:** 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

#### Organization Study ID Info
**ID:** VPM1002-DE-3.07CoV
#### Organization
**Class:** INDUSTRY
**Full Name:** Vakzine Projekt Management GmbH
#### Secondary ID Infos
**ID:** 2020-001675-33
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2021-10-12

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-10-26

**Type:** ACTUAL

**Last Update Submit Date:** 2021-10-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2021-10-12

**Type:** ACTUAL

#### Start Date
**Date:** 2020-06-18

**Type:** ACTUAL

**Status Verified Date:** 2021-10

#### Study First Post Date
**Date:** 2020-06-17
**Type:** ACTUAL
**Study First Submit Date:** 2020-06-16
**Study First Submit QC Date:** 2020-06-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** FGK Clinical Research GmbH

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Vakzine Projekt Management GmbH

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Infection, Respiratory Tract

**Keywords:**

- infectious respiratory diseases

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** 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.

##### Masking Info

**Masking:** TRIPLE

**Masking Description:** The reconstitution of trial intervention will be done by unblinded site personnel who will not be involved in the collection or evaluation of outcome data. Administration of the trial intervention will be done by blinded site personnel.

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 2038

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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.

**Intervention Names:**

- Biological: VPM1002

**Label:** VPM1002

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Physiological saline 0.1ml

**Intervention Names:**

- Biological: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- VPM1002

**Description:** 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).

**Name:** VPM1002

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** 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).

**Name:** Placebo

**Type:** BIOLOGICAL

### Outcomes Module

#### Primary Outcomes

**Measure:** Number of days with severe respiratory disease at hospital and/or at home

**Time Frame:** From day 0 to day 240

#### Secondary Outcomes

**Measure:** Cumulative incidence of hospital admissions

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of documented SARS-CoV-2 infection

**Time Frame:** From day 0 to day 240

**Measure:** Number of days with self-reported fever (≥ 38 ºC)

**Time Frame:** From day 0 to day 240

**Measure:** Number of days with self-reported acute respiratory symptoms

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of self-reported acute respiratory symptoms

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of death for any reason

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of death due to documented SARS-CoV-2 infection

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of ICU admission for any reason

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

**Time Frame:** From day 0 to day 240

**Measure:** Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection

**Time Frame:** From day 0 to day 240

### Eligibility Module

**Eligibility Criteria:** 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

**Healthy Volunteers:** True

**Minimum Age:** 60 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Stuttgart

**Country:** Germany

**Facility:** Hautarztpraxis Dres. Leitz & Kollegen

**State:** Baden-Württemberg

**Zip:** 70178

**Location 2:**

**City:** Cottbus

**Country:** Germany

**Facility:** MECS Cottbus GmbH

**State:** Brandenburg

**Zip:** 03050

**Location 3:**

**City:** Frankfurt

**Country:** Germany

**Facility:** Studienzentrum Dr. Keller

**State:** Hessen

**Zip:** 60389

**Location 4:**

**City:** Hannover

**Country:** Germany

**Facility:** Klinische Forschung Hannover Mitte GmbH

**State:** Niedersachsen

**Zip:** 30159

**Location 5:**

**City:** Hannover

**Country:** Germany

**Facility:** Medizinische Hochschule Hannover

**State:** Niedersachsen

**Zip:** 30625

**Location 6:**

**City:** Essen

**Country:** Germany

**Facility:** Medizentrum Essen Borbeck

**State:** Nordrhein-Westfalen

**Zip:** 45355

**Location 7:**

**City:** Mainz

**Country:** Germany

**Facility:** BAG Dres. med. Quist PartG

**State:** Rheinland-Pfalz

**Zip:** 55128

**Location 8:**

**City:** Leipzig

**Country:** Germany

**Facility:** SIBAmed GmbH & Co. KG

**State:** Sachsen

**Zip:** 04103

**Location 9:**

**City:** Erfurt

**Country:** Germany

**Facility:** SocraTec R&D GmbH

**State:** Thüringen

**Zip:** 99084

**Location 10:**

**City:** Berlin

**Country:** Germany

**Facility:** emovis GmbH

**Zip:** 10629

**Location 11:**

**City:** Berlin

**Country:** Germany

**Facility:** Klinische Forschung Berlin GbR

**Zip:** 10787

**Location 12:**

**City:** Hamburg

**Country:** Germany

**Facility:** Klinische Forschung Hamburg GmbH

**Zip:** 20253

#### Overall Officials

**Official 1:**

**Affiliation:** Vakzine Projekt Management GmbH

**Name:** Leander Grode, Dr. rer. nat.

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**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.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Blossey AM, Bruckner 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 Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study. Clin Infect Dis. 2023 Apr 3;76(7):1304-1310. doi: 10.1093/cid/ciac881.

**PMID:** 36358012

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M2561

- Name: COVID-19

- Relevance: LOW

- As Found: Unknown

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infectious

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Infectious Disease

- ID: M14957

- Name: Respiration Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: HIGH

- As Found: Infections, Respiratory Tract

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003141

- Term: Communicable Diseases

- ID: D000007239

- Term: Infections

- ID: D000012141

- Term: Respiratory Tract Infections

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M17360

- Name: Vaccines

- Relevance: LOW

- As Found: Unknown

- ID: M4793

- Name: BCG Vaccine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
