Back to results

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

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 1

Locations

South Africa

Study Type

Interventional

Intervention

VPM1002 live vaccine

commercially available live vaccine BCG

About this trial

This is an interventional prevention trial for Tuberculosis focused on measuring Tuberculosis, Vaccine, Live Vaccine, rBCG

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Farmovs-Parexel

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

VPM1002 in three dosages

BCG

Arm Description

Outcomes

Primary Outcome Measures

Safety: physical examination, vital signs, electrocardiogram, liver sonography, laboratory safety parameters, tolerability, recording of concomitant medication and adverse events

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)

Immunogenicity: ELISPOT for the number of IFN-g-secreting PBMC after restimulation with PPD

Immunogenicity: Whole Blood Assays (WBA): IFN-g-ELISA of supernatants of whole blood restimulated with PPD

Immunogenicity: Intracellular Cytokine Staining (ICS) for IFN-g, TNF-a and IL-2 in CD4+ and CD8+ lymphocytes upon stimulation with PPD

Immunogenicity: ICS with other triple combinations of markers in CD4+ and CD8+ lymphocytes upon stimulation with PPD

Immunogenicity: Antigen-85B (Ag85B) and BCG as recall antigens for ELISA, ELISPOT, WBA and ICS

Immunogenicity: serum antibodies against PPD or Ag85B

Full Information

NCT ID

NCT01113281

First Posted

April 27, 2010

Last Updated

November 18, 2011

Sponsor

Vakzine Projekt Management GmbH

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)

1. Study Identification

Unique Protocol Identification Number

NCT01113281

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2011

Overall Recruitment Status

Completed

Study Start Date

April 2010 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vakzine Projekt Management GmbH

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, Vaccine, Live Vaccine, rBCG

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VPM1002 in three dosages

Arm Type

Experimental

Arm Title

BCG

Arm Type

Active Comparator

Intervention Type

Biological

Intervention Name(s)

VPM1002 live vaccine

Intervention Type

Biological

Intervention Name(s)

commercially available live vaccine BCG

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

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