Dose-Escalation Study on Safety and Immunogenicity of VPM1002 in Comparison to BCG in Healthy Volunteers in South Africa

This study has been completed.
Sponsor:
Collaborators:
Farmovs-Parexel Bloemfontein, Republic of South Africa (Clinical Site)
Triclinium Johannesburg, RSA (Monitoring and Overall Management of the study)
University of Stellenbosch
HJ-CTC George, RSA (Statistics & Report)
Information provided by (Responsible Party):
Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier:
NCT01113281
First received: April 27, 2010
Last updated: November 18, 2011
Last verified: November 2011
  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 tuberculosis (TB) for residents in endemic areas and persons at risk in non-endemic areas. The new vaccine should be at least as potent as the current strain and should be safer than BCG (Kaufmann, 2007a; Grode et al., 2005). The vaccine is formulated as live lyophilised bacteria to be re-suspended before intradermal injection. The preceding clinical trial in 80 volunteers in Germany indicated immunogenicity and safety being sufficient for proceeding with the clinical development. Hence, the current study is commenced in South Africa, a country highly endemic for tuberculosis.

24 volunteers were randomly allocated to 4 groups each with 6 adult healthy volunteers.


Condition Intervention Phase
Tuberculosis
Biological: VPM1002 live vaccine
Biological: commercially available live vaccine 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 Ib Open Label, Randomized, Controlled, Dose-Escalation Study to Evaluate Safety and Immunogenicity of VPM1002 in Comparison With BCG in Healthy Volunteers in South Africa

Resource links provided by NLM:


Further study details as provided by Vakzine Projekt Management GmbH:

Primary Outcome Measures:
  • Safety: physical examination, vital signs, electrocardiogram, liver sonography, laboratory safety parameters, tolerability, recording of concomitant medication and adverse events [ Time Frame: baseline, days 2, 7, 14, 28, 56, and month 6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity: Interferon-gamma-ELISA (IFN-g-ELISA) in supernatants of peripheral blood mononuclear cells (PBMC) restimulated with tuberculin (PPD from Staten Serum Institute, Denmark) [ Time Frame: baseline, days 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: ELISPOT for the number of IFN-g-secreting PBMC after restimulation with PPD [ Time Frame: baseline, days 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: Whole Blood Assays (WBA): IFN-g-ELISA of supernatants of whole blood restimulated with PPD [ Time Frame: baseline, days 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: Intracellular Cytokine Staining (ICS) for IFN-g, TNF-a and IL-2 in CD4+ and CD8+ lymphocytes upon stimulation with PPD [ Time Frame: baseline, days 14, 28, 56 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 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: Antigen-85B (Ag85B) and BCG as recall antigens for ELISA, ELISPOT, WBA and ICS [ Time Frame: baseline, days 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]
  • Immunogenicity: serum antibodies against PPD or Ag85B [ Time Frame: baseline, days 14, 28, 56 and month 6 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2010
Study Completion Date: March 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VPM1002 in three dosages Biological: VPM1002 live vaccine
Active Comparator: BCG Biological: commercially available live vaccine BCG

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult volunteers 18 to 45 years of age
  • Volunteers must use acceptable contraception and avoid pregnancy for the duration of the study (6 months)
  • Healthy (medical history, physical examination, vital signs, ECG and laboratory tests at screening)
  • No signs of active or latent tuberculosis infection
  • BMI of 19 - 33 kg/m2
  • 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.
  • Reachable by phone during the whole study period (approximately 6 months).
  • Negative test for HIV1 and HIV2, hepatitis B surface antigen and antibody to hepatitis C virus.
  • No anamnestic evidence for a primary or secondary immunodeficiency.
  • No skin eczema lesion at the intended injection site.
  • No anamnestic predisposition for scarring badly or for keloid formation.
  • No other vaccination during eight weeks before the current study.
  • No participation in another clinical trial within 3 months before study vaccination and the 6 months of the current study.
  • No prior participation in a TB vaccine trial.
  • Able and willing to abstain from strenuous physical exercise 24 hours before screening examination, and 24 hours before vaccination

Exclusion Criteria:

  • History of prior TB disease
  • History of anaphylaxis or severe allergic reactions
  • Known allergies to any component of the investigational or reference product or known history of severe skin reaction against the Tuberculin test
  • Presence of any person in the household of the volunteer with active tuberculosis disease
  • Tuberculin-PPD-in-vivo-test equal or more than 10 mm before baseline
  • systemic disorders which could interfere with the interpretation of the study results or compromise the health of the volunteers
  • BCG-vaccination during 10 years before study vaccination
  • Acute fever or fever in the last 7 days before dosing
  • Any malignant condition
  • Concomitant treatment with medication that may affect immune function during 3 months before study vaccination and the 6 months of current study. No oral antibiotics during the 14 days before study vaccination and no injectable antibiotics during the 28 days prior to vaccination.
  • Treatment with blood products in the past 6 months up to end of study.
  • Any clinically significant laboratory abnormalities on screened blood samples.
  • A history of drug or alcohol abuse
  • Positive test for drugs of abuse on urine testing at screening
  • Blood donation for non study-related purposes within 3 months before and during the entire duration of the study
  • Clinically relevant result from sonographic liver imaging
  • Professional or regular contact with live 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: NCT01113281

Locations
South Africa
Farmovs-Parexel
Bloemfontein, South Africa, 9301
Sponsors and Collaborators
Vakzine Projekt Management GmbH
Farmovs-Parexel Bloemfontein, Republic of South Africa (Clinical Site)
Triclinium Johannesburg, RSA (Monitoring and Overall Management of the study)
University of Stellenbosch
HJ-CTC George, RSA (Statistics & Report)
Investigators
Principal Investigator: Mada Ferreira, MD Farmovs-Parexel, Bloemfontein, RSA
  More Information

No publications provided

Responsible Party: Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier: NCT01113281     History of Changes
Other Study ID Numbers: VPM1002-ZA-1.10TB, DOH-27-0210-3083
Study First Received: April 27, 2010
Last Updated: November 18, 2011
Health Authority: South Africa: Medicines Control Council

Keywords provided by Vakzine Projekt Management GmbH:
Tuberculosis
Vaccine
Live Vaccine
rBCG

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

ClinicalTrials.gov processed this record on October 23, 2014