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

Infection, Respiratory Tract Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04435379
• Other study ID #: VPM1002-DE-3.07CoV
• Secondary ID: 2020-001675-33
• Status: Completed
• Phase: Phase 3
• Start date: June 18, 2020
• Est. completion date: October 12, 2021

Study information

• Verified date: October 2021
• Source: Vakzine Projekt Management GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 2038
• Est. completion date: October 12, 2021
• Est. primary completion date: October 12, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection, Respiratory Tract
• Infections
• Respiratory Tract Infections

Intervention

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
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).

Locations

Country	Name	City	State
Germany	emovis GmbH	Berlin
Germany	Klinische Forschung Berlin GbR	Berlin
Germany	MECS Cottbus GmbH	Cottbus	Brandenburg
Germany	SocraTec R&D GmbH	Erfurt	Thüringen
Germany	Medizentrum Essen Borbeck	Essen	Nordrhein-Westfalen
Germany	Studienzentrum Dr. Keller	Frankfurt	Hessen
Germany	Klinische Forschung Hamburg GmbH	Hamburg
Germany	Klinische Forschung Hannover Mitte GmbH	Hannover	Niedersachsen
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	SIBAmed GmbH & Co. KG	Leipzig	Sachsen
Germany	BAG Dres. med. Quist PartG	Mainz	Rheinland-Pfalz
Germany	Hautarztpraxis Dres. Leitz & Kollegen	Stuttgart	Baden-Württemberg

Sponsors (2)

Lead Sponsor	Collaborator
Vakzine Projekt Management GmbH	FGK Clinical Research GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of days with severe respiratory disease at hospital and/or at home		From day 0 to day 240
Secondary	Cumulative incidence of hospital admissions		From day 0 to day 240
Secondary	Cumulative incidence of documented SARS-CoV-2 infection		From day 0 to day 240
Secondary	Number of days with self-reported fever (= 38 ºC)		From day 0 to day 240
Secondary	Number of days with self-reported acute respiratory symptoms		From day 0 to day 240
Secondary	Cumulative incidence of self-reported acute respiratory symptoms		From day 0 to day 240
Secondary	Cumulative incidence of death for any reason		From day 0 to day 240
Secondary	Cumulative incidence of death due to documented SARS-CoV-2 infection		From day 0 to day 240
Secondary	Cumulative incidence of ICU admission for any reason		From day 0 to day 240
Secondary	Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection		From day 0 to day 240
Secondary	Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection		From day 0 to day 240