NCT02391415

Brief Summary

Goal of Serum Institute of India Limited (SIIL) 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. The preceding phase-IIa trial was the first investigation of VPM1002 in newborn infants in a high burden setting in South Africa. The vaccination of HIV-unexposed infants with VPM1002 indicated again safety, tolerability and immunogenicity sufficient to proceed in HIV-exposed infants. The current study is a multiple site trial in South Africa to evaluate safety and immunogenicity in HIV-unexposed and -exposed newborn infants.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
416

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2015

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 5, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

March 18, 2015

Completed
3 months until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2017

Completed
Last Updated

April 18, 2018

Status Verified

April 1, 2018

Enrollment Period

2.4 years

First QC Date

March 5, 2015

Last Update Submit

April 17, 2018

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

  • The difference between the VPM1002 and BCG vaccination groups in the incidence of grade 3 and 4 adverse drug reactions and IMP-related ipsilateral or generalised lymphadenopathy of 10mm or greater (diameter).

    up to 12 months

Study Arms (5)

HIV-unexposed infants VPM1002

EXPERIMENTAL

HIV-unexposed infants vaccinated with VPM1002

Biological: VPM1002

HIV-unexposed infants BCG

ACTIVE COMPARATOR

HIV-unexposed infants vaccinated with BCG

Biological: BCG

HIV-unexposed infants VPM1002(Hyg+)

EXPERIMENTAL

HIV-unexposed infants vaccinated with VPM1002(Hyg+)

Biological: VPM1002(Hyg+)

HIV-exposed infants BCG

ACTIVE COMPARATOR

HIV-exposed infants vaccinated with BCG

Biological: BCG

HIV-exposed infants VPM1002

EXPERIMENTAL

HIV-exposed infants vaccinated with VPM1002

Biological: VPM1002

Interventions

VPM1002BIOLOGICAL

Tuberculosis vaccine

Also known as: recombinant BCG for TB
HIV-exposed infants VPM1002HIV-unexposed infants VPM1002
BCGBIOLOGICAL

commercially available live vaccine BCG

HIV-exposed infants BCGHIV-unexposed infants BCG
VPM1002(Hyg+)BIOLOGICAL

Tuberculosis vaccine

Also known as: recombinant BCG for TB
HIV-unexposed infants VPM1002(Hyg+)

Eligibility Criteria

AgeUp to 12 Days
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Maternal:
  • The infant's mother must be aged 18 years or older at 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 active TB 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
  • 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 12 months on-study period as well as the 24 month structured medical surveillance period.
  • For HIV-unexposed group: 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.
  • For the HIV-exposed group: The infant's mother must test positive 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 have enrolled for standard antiretroviral therapy (ART) at least 3 months before the participating infant's birth and must have a viral load at screening below 1000 copies/ml. The use of ART, including combination antiretroviral therapy (cART) and preventive mother to child transmission (PMTCT) must be documented. CD4+ T cell count and HIV viral load must be documented.
  • 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 12 months of the current study.
  • The infant's mother must have no known history of immunodeficiency, except for HIV.
  • Infant:
  • Healthy male or female newborn infants aged 0 to 12 days.
  • Infants must have a birth weight of 2500 - 4200 g and an Apgar score of \> 7 at 5 minutes or earlier.
  • No eczema or other significant skin lesion or infection at the intended injection site.
  • +3 more criteria

You may not qualify if:

  • Maternal:
  • Known presence of any person in the household of the mother and newborn infant, or any recent visitor to the household with recently diagnosed, active tuberculosis disease (within last 3 months).
  • Treatment of the mother with blood products in the 6 months prior to or during the birth of the participating infant.
  • For the HIV-unexposed group: Positive test for HIV-1 either during the current pregnancy or at screening.
  • For the HIV-exposed group: Negative test for HIV-1 either during the current pregnancy or at screening.
  • 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.
  • 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 by digital thermometer on at least 2 occasions not less than 6 hours apart.
  • 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 by digital thermometer on at least 2 occasions not less than 6 hours apart.
  • Clinically suspected newborn sepsis.
  • Any malignant condition.
  • Any severe congenital malformation.
  • Treatment of the infant with blood products.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Children's Infectious Diseases Clinical Research Unit, Tygerberg Hospital

Cape Town, South Africa

Location

Desmond Tutu TB Centre

Cape Town, South Africa

Location

South African Tuberculosis Vaccine Initiative

Cape Town, South Africa

Location

The Respiratory and Meningeal Pathogens Reserach Unit

Johannesburg, South Africa

Location

Related Publications (1)

  • Cotton MF, Madhi SA, Luabeya AK, Tameris M, Hesseling AC, Shenje J, Schoeman E, Hatherill M, Desai S, Kapse D, Bruckner S, Koen A, Jose L, Moultrie A, Bhikha S, Walzl G, Gutschmidt A, Kotze LA, Allies DL, Loxton AG, Shaligram U, Abraham M, Johnstone H, Grode L, Kaufmann SHE, Kulkarni PS. Safety and immunogenicity of VPM1002 versus BCG in South African newborn babies: a randomised, phase 2 non-inferiority double-blind controlled trial. Lancet Infect Dis. 2022 Oct;22(10):1472-1483. doi: 10.1016/S1473-3099(22)00222-5. Epub 2022 Jun 27.

    PMID: 35772447DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

VPM1002 recombinant BCG vaccine

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 5, 2015

First Posted

March 18, 2015

Study Start

June 1, 2015

Primary Completion

November 1, 2017

Study Completion

November 1, 2017

Last Updated

April 18, 2018

Record last verified: 2018-04

Locations

ZA(4)