Study to Evaluate Safety and Immunogenicity of VPM1002 in Comparison With BCG in Newborn Infants in South Africa

This study has been completed.
Sponsor:
Collaborators:
Children's Infectious Diseases Clinical Research Unit (KID-CRU), South Africa
Triclinium Johannesburg, South Africa
University of Stellenbosch
HJ-CTC George, South Africa
Information provided by (Responsible Party):
Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier:
NCT01479972
First received: November 18, 2011
Last updated: October 28, 2013
Last verified: October 2013
  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 trials in 80 volunteers in Germany and 24 volunteers in Bloemfontein, South Africa indicated immunogenicity and safety being sufficient for proceeding with the clinical development in newborn infants. Hence, the current study is commenced at Stellenbosch University, South Africa. This is the first investigation of VPM1002 in newborn infants.


Condition Intervention Phase
Tuberculosis
Biological: VPM1002
Biological: BCG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Open Label, Randomized, Controlled Study to Evaluate Safety and Immunogenicity of VPM1002 in Comparison With BCG in HIV-unexposed, BCG Naive Newborn Infants in South Africa

Resource links provided by NLM:


Further study details as provided by Vakzine Projekt Management GmbH:

Primary Outcome Measures:
  • Safety [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
    Safety and tolerability as assessed by monitoring of adverse events (incidence, time profile, other profiles, and including local or regional reactions at the vaccination site), physical examination, vital signs, standard laboratory safety parameters, including haematology, clinical chemistry and urinalysis.


Secondary Outcome Measures:
  • Immunogenicity [ Time Frame: baseline, day 14, week 6, 12, 18, month 6 ] [ Designated as safety issue: No ]
    IFN-gamma-WB-ELISA: concentration of IFN-gamma per ml supernatant after stimulation. ICS (FACS): number of CD4+ T-lymphocytes ("single-positive-cells", "double-positive-cells", "triple-positive-cells", "multi-positive-cells (positive for at least two of IFN-gamma, TNF-alpha or IL-2) after 16 hours stimulation; per total number of lymphocytes. ICS (FACS): number of CD8+ T-lymphocytes("single-positive-cells", "double-positive-cells", "triple-positive-cells", "multi-positive-cells (positive for at least two of IFN-gamma, TNF-alpha or IL-2) after 16 hours stimulation.


Enrollment: 48
Study Start Date: November 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VPM1002 Biological: VPM1002
Tuberculosis vaccine
Active Comparator: BCG Biological: BCG
commercially available live vaccine BCG

  Eligibility

Ages Eligible for Study:   up to 8 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Maternal:

  1. The infant's mother must be aged 18 years or older at the time of screening.
  2. The infant's mother must be able and willing to comply with the study protocol, available and willing to allow her child to complete all the study assessments and must have signed an Informed Consent form that has been approved by all relevant Ethics Committee/s.
  3. The infant's mother must not have any symptoms or signs of either active TB or latent tuberculosis infection as indicated by:

    • History of cough for more than two weeks, fever, weight loss, breathlessness, chest pain, blood in sputum, night sweats and loss of appetite, and/or
    • Mantoux Tuberculin PPD skin test greater than or equal to 10 mm
  4. The infant's mother should not be planning to relocate from the research site area and should be reachable by phone during the whole study period i.e. for the 6 month on-study period as well as the 30 month structured medical surveillance period.
  5. The infant's mother must test negative for HIV-1 (ELISA 4th generation) within the period from 2 weeks prior to the infant's birth to vaccination of the infant with the investigational product.
  6. The infant's mother must test negative for Hepatitis B and Syphilis serology at screening.
  7. The infant's mother should have no history or evidence of Diabetes Mellitus.
  8. No participation of the infant's mother in a clinical trial within 3 months prior to the birth of the participating infant. In addition, if breast-feeding, no participation in another clinical trial during the 6 months of the current study.
  9. The infant's mother must have no known history of immunodeficiency.

Infant:

  1. Healthy full-term male or female newborn infants aged 0 to 8 days.
  2. Infants must have a birth weight of 3000 - 4000 g and an Apgar score of > 9 at 5 minutes.
  3. No eczema or other significant skin lesion or infection at the intended injection site.
  4. No routine BCG vaccination administered (as per vaccination record)
  5. Infants must have received Oral Polio Vaccine as part of the routine South African Expanded Programme on Immunisation (EPI) Childhood Immunisation schedule, and must adhere to the subsequent EPI schedule for the entire study period, except for the BCG vaccination at birth.
  6. No participation of the infant in another clinical trial before study vaccination and during the 6 months of the current study.

Exclusion Criteria:

Maternal:

  1. Known presence of any person in the household of the mother and newborn infant, or any visitor to the household with reported active tuberculosis disease.
  2. Treatment of the mother with blood products in the 6 months prior to or during the birth of the participating infant.
  3. Positive test for HIV-1 either during the current pregnancy or at screening.
  4. Positive screening test for Hepatitis B or Syphilis.
  5. History or evidence of Diabetes Mellitus.
  6. Presence of any symptoms or signs of either active TB or latent tuberculosis infection as indicated by:

    • History of cough for more than two weeks, fever, weight loss, breathlessness, chest pain, blood in sputum, night sweats and loss of appetite, and/or
    • Mantoux Tuberculin PPD skin test greater than or equal to 10 mm (read 48-72hrs post-test)
  7. Presence of signs or symptoms of any reported acute infectious disease at the time of screening.
  8. Any reported or suspected substance abuse.

Infant:

  1. History or evidence of any systemic disease on physical examination or any acute, chronic or intercurrent illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.

    Note: Neonatal jaundice which is not considered by the investigator to be clinically significant will not represent exclusion.

  2. Vaccination with routine BCG before study vaccination.
  3. Fever within the period post birth and prior to dosing. For the purposes of this protocol, fever in the infant will be defined as an axillary body temperature > 38.0°C measured with a digital thermometer on at least 2 occasions not less than 6 hours apart.
  4. Hypothermia within the period post birth and prior to dosing. For the purposes of this protocol, hypothermia in the infant will be defined as an axillary body temperature < 36.0°C measured with a digital thermometer on at least 2 occasions not less than 6 hours apart.
  5. Clinically suspected neonatal sepsis.
  6. Any malignant condition.
  7. Any severe congenital malformation.
  8. Concomitant treatment with medication that may significantly affect immune function (e.g. systemic corticoids, immunosuppressive drugs) before study vaccination. Antibiotics given before study vaccination would further constitute exclusion.
  9. Treatment of the infant with blood products.
  10. Any clinically significant laboratory abnormalities on screening blood samples or urinalysis.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01479972

Locations
South Africa
Children's Infectious Diseases Clinical Research Unit, Tygerberg Hospital
Cape Town, South Africa
Sponsors and Collaborators
Vakzine Projekt Management GmbH
Children's Infectious Diseases Clinical Research Unit (KID-CRU), South Africa
Triclinium Johannesburg, South Africa
University of Stellenbosch
HJ-CTC George, South Africa
Investigators
Principal Investigator: Mark Cotton, MD, Professor Children's Infectious Diseases Clinical Research Unit (KID-CRU), Tygerberg, South Africa
  More Information

No publications provided

Responsible Party: Vakzine Projekt Management GmbH
ClinicalTrials.gov Identifier: NCT01479972     History of Changes
Other Study ID Numbers: VPM1002-ZA-2.12TB, DOH-27-0911-3677
Study First Received: November 18, 2011
Last Updated: October 28, 2013
Health Authority: South Africa: Medicines Control Council

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

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

ClinicalTrials.gov processed this record on April 15, 2014