TuberculosisPhase 1NCT01113281
Dose-Escalation Study on Safety and Immunogenicity of VPM1002 in Comparison to BCG in Healthy Volunteers in South Africa
A Phase 1 study testing VPM1002 live vaccine and commercially available live vaccine BCG in people with Tuberculosis, run by Serum Life Science Europe GmbH at 1 site in South Africa.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- VPM1002 live vaccine and commercially available live vaccine BCG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSouth Africa
- Study dates
- Apr 2010to Mar 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Tuberculosis
- Being tested
- VPM1002 live vaccine, commercially available live vaccine BCG
- Keywords
- Tuberculosis, Vaccine, Live Vaccine, rBCG
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VPM1002 live vaccineBiological
commercially available live vaccine BCGBiological
| Study group | Role | What they receive |
|---|---|---|
| VPM1002 in three dosages | Experimental | Not described Receives: Biological: VPM1002 live vaccine |
| BCG | Active comparator | Not described Receives: Biological: commercially available live vaccine BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: physical examination, vital signs, electrocardiogram, liver sonography, laboratory safety parameters, tolerability, recording of concomitant medication and adverse events
Measured: baseline, days 2, 7, 14, 28, 56, and month 6
Secondary outcomes (7)
Immunogenicity: Interferon-gamma-ELISA (IFN-g-ELISA) in supernatants of peripheral blood mononuclear cells (PBMC) restimulated with tuberculin (PPD from Staten Serum Institute, Denmark)
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: ELISPOT for the number of IFN-g-secreting PBMC after restimulation with PPD
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: Whole Blood Assays (WBA): IFN-g-ELISA of supernatants of whole blood restimulated with PPD
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: Intracellular Cytokine Staining (ICS) for IFN-g, TNF-a and IL-2 in CD4+ and CD8+ lymphocytes upon stimulation with PPD
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: ICS with other triple combinations of markers in CD4+ and CD8+ lymphocytes upon stimulation with PPD
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: Antigen-85B (Ag85B) and BCG as recall antigens for ELISA, ELISPOT, WBA and ICS
Measured: baseline, days 14, 28, 56 and month 6
Immunogenicity: serum antibodies against PPD or Ag85B
Measured: baseline, days 14, 28, 56 and month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionDec 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Serum Life Science Europe GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- 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)
- Responsible party
- Sponsor
- Investigators
- Mada Ferreira, MD, Principal investigator, Farmovs-Parexel, Bloemfontein, RSA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01113281
- Sponsor's protocol ID
- VPM1002-ZA-1.10TB
- Other IDs
- DOH-27-0210-3083
- Status last verified
- Nov 2011
- First submitted
- 27 Apr 2010
- Last updated
- 21 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01113281
- Acronym / sponsor ID
- VPM1002-ZA-1.10TB
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, Vaccine, Live Vaccine, rBCG
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Serum Life Science Europe GmbHIndustry (pharma, biotech, devices)
- 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)
- Study start
- Apr 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 29 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VPM1002 in three dosages | Experimental | Biological: VPM1002 live vaccine |
| BCG | Active comparator | Biological: commercially available live vaccine BCG |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VPM1002 live vaccine | Biological | VPM1002 in three dosages |
| commercially available live vaccine BCG | Biological | BCG |
Primary outcome
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
7 secondary outcomes
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
Immunogenicity: ELISPOT for the number of IFN-g-secreting PBMC after restimulation with PPD
Time frame: baseline, days 14, 28, 56 and month 6
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
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
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
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
Immunogenicity: serum antibodies against PPD or Ag85B
Time frame: baseline, days 14, 28, 56 and month 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mada Ferreira, MD principal investigator
Farmovs-Parexel, Bloemfontein, RSA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VPM1002 live vaccine and commercially available live vaccine BCG in people with Tuberculosis, run by Serum Life Science Europe GmbH at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2011.