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

NCT01479972 | Completed Phase 2 DMC

• 2 other identifiers: VPM1002-ZA-2.12TBDOH-27-0911-3677
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Tuberculosis

Keywords

Tuberculosis; Vaccine; Live vaccine; rBCG

Outcome Measures

Primary Outcomes (1)

• Safety

  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.

  Six months

Secondary Outcomes (1)

• Immunogenicity

  baseline, day 14, week 6, 12, 18, month 6

Study Arms (2)

VPM1002

EXPERIMENTAL

Biological: VPM1002

BCG

ACTIVE COMPARATOR

Biological: BCG

Interventions

VPM1002 BIOLOGICAL

Tuberculosis vaccine

VPM1002

BCG BIOLOGICAL

commercially available live vaccine BCG

BCG

Eligibility Criteria

• Age: Up to 8 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Maternal:
• The infant's mother must be aged 18 years or older at the time of screening.
• 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.
• 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
• 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.
• 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.
• The infant's mother must test negative for Hepatitis B and Syphilis serology at screening.
• The infant's mother should have no history or evidence of Diabetes Mellitus.
• 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.
• The infant's mother must have no known history of immunodeficiency.
• Infant:
• Healthy full-term male or female newborn infants aged 0 to 8 days.
• Infants must have a birth weight of 3000 - 4000 g and an Apgar score of \> 9 at 5 minutes.

You may not qualify if:

• Maternal:
• 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.
• Treatment of the mother with blood products in the 6 months prior to or during the birth of the participating infant.
• Positive test for HIV-1 either during the current pregnancy or at screening.
• Positive screening test for Hepatitis B or Syphilis.
• History or evidence of Diabetes Mellitus.
• 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)
• Presence of signs or symptoms of any reported acute infectious disease at the time of screening.
• Any reported or suspected substance abuse.
• Infant:
• 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.
• Vaccination with routine BCG before study vaccination.
• 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.

Sponsors & Collaborators

• Serum Life Science Europe GmbH: lead
• Children's Infectious Diseases Clinical Research Unit (KID-CRU), South Africa: collaborator
• Triclinium Johannesburg, South Africa: collaborator
• University of Stellenbosch: collaborator
• HJ-CTC George, South Africa: collaborator

Study Sites (1)

Children's Infectious Diseases Clinical Research Unit, Tygerberg Hospital

Cape Town, South Africa

Location

Related Publications (1)

• Loxton AG, Knaul JK, Grode L, Gutschmidt A, Meller C, Eisele B, Johnstone H, van der Spuy G, Maertzdorf J, Kaufmann SHE, Hesseling AC, Walzl G, Cotton MF. Safety and Immunogenicity of the Recombinant Mycobacterium bovis BCG Vaccine VPM1002 in HIV-Unexposed Newborn Infants in South Africa. Clin Vaccine Immunol. 2017 Feb 6;24(2):e00439-16. doi: 10.1128/CVI.00439-16. Print 2017 Feb.

  PMID: 27974398 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

VPM1002 recombinant BCG vaccine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Mark Cotton, MD, Professor

  Children's Infectious Diseases Clinical Research Unit (KID-CRU), Tygerberg, South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2011
• First Posted: November 28, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 29, 2013

Record last verified: 2013-10

Locations

ZA (1)