Dose-Escalation Study on Safety and Immunogenicity of VPM1002 in Comparison With BCG in Healthy Male Volunteers

This study has been completed.
Sponsor:
Information provided by:
Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier:
NCT00749034
First received: September 5, 2008
Last updated: May 19, 2010
Last verified: April 2010
  Purpose

Goal of VPM is the development of a recombinant urease C-deficient listeriolysin expressing BCG vaccine strain (VPM1002) as a safe, well tolerated and efficacious vaccine against TB for residents in endemic areas and persons at risk in non-endemic areas. The new live vaccine VPM1002 should be at least as potent as the currently used BCG vaccine and should cause fewer side effects (Kaufmann, 2007; Grode et al., 2005). It is formulated as lyophilised bacteria to be resuspended before intradermal injection. First application of VPM1002 in human male volunteers will evaluate its safety, local and systemic tolerability as well as its immunogenicity. The study has a dose-escalating sequential design with comparison to commercially available BCG. 80 volunteers in Germany will randomly be allocated to 4 groups each with 20 volunteers stratified for their history of BCG-vaccination.


Condition Intervention Phase
Tuberculosis
Healthy
Biological: VPM1002
Biological: BCG
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Open Label, Randomized, Controlled, Dose-Escalation Study to Evaluate Safety and Immunogenicity of VPM1002 in Comparison With BCG in Healthy Male Volunteers Stratified for History of BCG-Vaccination

Resource links provided by NLM:


Further study details as provided by Vakzine Projekt Management GmbH:

Primary Outcome Measures:
  • Safety: physical examination, vital signs, ECG, liver sonography, chest X-ray, laboratory safety parameters (including haematology, coagulation, clinical chemistry and urinalysis), tolerability, recording of concomitant medication and adverse events [ Time Frame: days -1, 1, 2, 3, 5, 11, 29, 57 and month 6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity: LST for PPD with subsequent IFN-gamma specific ELISA on supernatants of PBMC [ Time Frame: baseline, days 29, 57, month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: ELISPOT for the number of IFN-gamma secreting PBMC after stimulation with PPD [ Time Frame: baseline, days 29, 57, month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: whole blood stimulated with PPD and measuring IFN-gamma in the plasma by ELISA [ Time Frame: baseline, days 29, 57, month 6 ] [ Designated as safety issue: No ]
  • ICS for IFN-gamma, TNF-alpha and IL-2 in CD4+ and CD8+ lymphocytes upon stimulation with PPD [ Time Frame: baseline, days 29, 57 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: ICS with other triple combinations of markers in CD4+ and CD8+ lymphocytes upon stimulation with PPD [ Time Frame: baseline, days 29, 57 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: TB85B as recall antigen for ELISA, ELISPOT, WBA and ICS [ Time Frame: baseline, days 29, 57 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: serum antibodies against PPD or AG85B [ Time Frame: baseline, days 29, 57 and month 6 ] [ Designated as safety issue: No ]

Enrollment: 80
Study Start Date: September 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
VPM1002 in three dosages
Biological: VPM1002
live vaccine
Active Comparator: 2
BCG
Biological: BCG
commercially available live vaccine BCG

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male volunteers 18 to 55 years of age.
  2. Healthy (medical history, physical examination, vital signs, ECG and laboratory tests at screening).
  3. No signs of active or latent tuberculosis infection.
  4. BMI of 19 - 30 kg/m2.
  5. Subjects must be able and willing to comply with the study protocol, available and willing to complete all study measurements and have signed an Informed Consent form approved by the Ethics Committee.
  6. Intention not to travel to endemic regions for tuberculosis (such as Africa, Asia, former USSR) and reachable by phone during the whole study period (6 months).
  7. Negative test for HIV1 and HIV2, hepatitis B surface antigen and antibody to hepatitis C virus .
  8. No anamnestic evidence for a primary or secondary immunodeficiency.
  9. No skin eczema lesion at the intended injection site.
  10. No anamnestic predisposition for scarring badly or for keloid formation.
  11. No other vaccination during eight weeks before and during the follow-up period of the current study. If a vaccination is necessary during this period, the volunteer will be withdrawn from the study.
  12. No participation in another clinical trial within 3 months before study vaccination and the 6 months of the current study.
  13. Able and willing to abstain from physical exercise 24 hours before screening examination, and from 24 hours before admission until discharge from the clinic.
  14. No blood donation for non study-related purposes during the entire duration of the study.
  15. normal sonographic liver imaging

Exclusion Criteria:

For the group of volunteers who were vaccinated with a BCG vaccine:

• Tuberculin-PPD-in-vivo-test equal or more than 10 mm at baseline

For the group of naive volunteers:

• Tuberculin-PPD-in-vivo-Test equal or more than 1 mm at baseline

For all volunteers

  1. systemic disorders which could interfere with the interpretation of the study results or compromise the health of the volunteers.
  2. BCG-vaccination during 10 years before study vaccination.
  3. Acute fever or fever in the last 7 days before dosing.
  4. Any malignant condition.
  5. Concomitant treatment with medication that may affect immune function during 3 months before study vaccination and the 6 months of current study.
  6. Treatment with blood products or Immunoglobulins in the past 6 months up to end of study.
  7. Any clinically significant laboratory abnormalities on screened blood samples.
  8. A history of drug or alcohol abuse.
  9. History of anaphylaxis or severe allergic reactions.
  10. Positive test for drugs of abuse on urine testing at screening or admission.
  11. Known allergies to any component of the investigational or reference product or known history of severe skin reaction against the Tuberculin test.
  12. Professional or regular contact with life animals for food production.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00749034

Locations
Germany
Focus Clinical Drug Development GmbH
Neuss, Germany, 41460
Sponsors and Collaborators
Vakzine Projekt Management GmbH
Investigators
Principal Investigator: Andreas Schrödter, MD FOCUS CDD GmbH
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Hans-Heinrich Henneicke - v. Zepelin / CPM, Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier: NCT00749034     History of Changes
Other Study ID Numbers: VPM1002-GE-1.01TB
Study First Received: September 5, 2008
Last Updated: May 19, 2010
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Vakzine Projekt Management GmbH:
Safety
Immunogenicity
Tuberculosis
Vaccination
Vaccination against tuberculosis
Safety and immunogenicity of VPM1002 in comparison with BCG

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on July 20, 2014