Trial to Investigate the Effect of Schistosoma Mansoni Infection on the Response to Vaccination With MVA85A in BCG-vaccinated African Adolescents

NCT ID: NCT02178748

Last Updated: 2015-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-01-31

Brief Summary

Mycobacterium tuberculosis (M. tb) is a pathogen with worldwide distribution which infects humans causing tuberculosis (TB), a transmissible disease resulting in very high mortality and morbidity; development of an effective vaccine is a global health priority.

Over a billion people worldwide are infected with one or more helminths. Helminths are parasitic worms, of which Schistosoma mansoni is one species. There is some evidence that helminth infection may affect a person's response to a vaccine. In this trial the investigators hope to investigate whether Schistosoma mansoni infection affects adolescents' responses to a candidate TB vaccine called MVA85A, as adolescents are a crucial target group for an effective TB vaccine.

Conditions

Tuberculosis

Keywords

Tuberculosis; Phase II; MVA85A; Schistosoma mansoni

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1

Group 1 (Schistosoma mansoni uninfected): 12-24 BCG-vaccinated volunteers with no helminth infection. Single dose of 1x10\^8pfu MVA85A intramuscular vaccination at D0.

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

Single dose of 1x10\^8pfu MVA85A intramuscular vaccination

Group 2

Group 2 (Schistosoma mansoni infected): 12-24 BCG-vaccinated volunteers with helminth infection. Single dose of 1x10\^8pfu MVA85A intramuscular vaccination at D0.

Group Type: EXPERIMENTAL

MVA85A

Intervention Type: BIOLOGICAL

Single dose of 1x10\^8pfu MVA85A intramuscular vaccination

Interventions

MVA85A

Single dose of 1x10\^8pfu MVA85A intramuscular vaccination

Intervention Type: BIOLOGICAL

Other Intervention Names

Modified Vaccinia Ankara 85A; AERAS-485

Eligibility Criteria

Inclusion Criteria

Participants must meet all of the following criteria to enter the trial:

• Healthy adolescents aged 12-17 years (both male and female)
• Resident in the study area for the duration of the study period
• Confirmation of prior vaccination with BCG not less than 6 months prior to projected study vaccination date (by visible BCG scar on examination or written documentation)
• No relevant findings in medical history or on physical examination
• Written informed consent by parent or guardian
• Written informed assent by subject
• Refrain from blood donation during the trial
• Agree to avoid pregnancy for the duration of the trial (female only)
• Able and willing (in the Investigator's opinion) to comply with all the study requirements
• Stool sample negative for S. mansoni (group 1) or positive for S. mansoni infection (group 2), based on the results of the Kato Katz stool analysis
• Willing to delay treatment for schistosomiasis for at least one month (group 2)

Exclusion Criteria

Participants may not enter the trial if ANY of the following apply:

• Clinical, radiological, or laboratory evidence of current active TB disease
• Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
• Previous treatment for active or latent tuberculosis infection
• Shared a residence within one year prior to day 0 with an individual on anti-tuberculosis treatment or with culture or smear-positive pulmonary tuberculosis
• Received a TST within 90 days prior to day 0
• Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness, drug or alcohol abuse
• History of serious psychiatric condition or disorder
• Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents within 2 months prior to enrolment
• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study vaccine, including eggs
• Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the study
• Positive HBsAg, HCV or HIV antibodies
• Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 30 days prior to dosing with the study vaccine, or planned use during the study period
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
• Female currently lactating, confirmed pregnancy or intention to become pregnant during the trial period
• Screening blood sample positive for malaria or Mansonella perstans by microscopy
• Schistosoma mansoni infection intensity greater than 2000 eggs per gram of stool
• Any of the three screening stool samples positive for any helminths on Kato Katz examinations or for S. mansoni or Strongyloides stercoralis by PCR (group 1); or any of the three screening stool samples positive for helminths other than S. mansoni on Kato Katz examinations or for Strongyloides stercoralis by PCR (group 2)
• Screening urine sample positive for S. mansoni infection (group 1)
• Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the subject at risk or may influence the result of the trial or may affect the subject's ability to participate in the trial

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

MRC/UVRI and LSHTM Uganda Research Unit

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helen McShane

Role: STUDY_DIRECTOR

University of Oxford

Alison Elliot

Role: PRINCIPAL_INVESTIGATOR

MRC/UVRI and LSHTM Uganda Research Unit

Locations

MRC/UVRI Uganda Research Unit on AIDS

Entebbe, , Uganda

Countries

Uganda

References

Wajja A, Namutebi M, Apule B, Oduru G, Kiwanuka S, Akello M, Nassanga B, Kabagenyi J, Mpiima J, Vermaak S, Lawrie A, Satti I, Verweij J, Cose S, Levin J, Kaleebu P, Tukahebwa E, McShane H, Elliott AM. Lessons from the first clinical trial of a non-licensed vaccine among Ugandan adolescents: a phase II field trial of the tuberculosis candidate vaccine, MVA85A. Wellcome Open Res. 2018 Sep 19;3:121. doi: 10.12688/wellcomeopenres.14736.1. eCollection 2018.

Reference Type: DERIVED

PMID: 30687792 (View on PubMed)

Wajja A, Kizito D, Nassanga B, Nalwoga A, Kabagenyi J, Kimuda S, Galiwango R, Mutonyi G, Vermaak S, Satti I, Verweij J, Tukahebwa E, Cose S, Levin J, Kaleebu P, Elliott AM, McShane H. The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial. PLoS Negl Trop Dis. 2017 May 4;11(5):e0005440. doi: 10.1371/journal.pntd.0005440. eCollection 2017 May.

Reference Type: DERIVED

PMID: 28472067 (View on PubMed)

Other Identifiers

TB036

Identifier Type: -

Identifier Source: org_study_id