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

NCT02178748 | Completed Phase 2

• 1 other identifier: TB036
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• T cell immunogenicity by gamma-interferon ELISPOT of Ag85A response.

  To compare T cell immunogenicity in adolescents with and without S. mansoni infection.

  8 weeks

Secondary Outcomes (1)

• Evaluation of cytokines in supernatant of stimulated cells using Luminex and flow cytometry of Ag85A response.

  8 weeks

Other Outcomes (1)

• Actively and passively collected data on adverse events.

  8 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

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

Biological: MVA85A

Group 2

EXPERIMENTAL

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

Biological: MVA85A

Interventions

MVA85A BIOLOGICAL

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

Also known as: Modified Vaccinia Ankara 85A, AERAS-485

Group 1; Group 2

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• MRC/UVRI and LSHTM Uganda Research Unit: collaborator

Study Sites (1)

MRC/UVRI Uganda Research Unit on AIDS

Entebbe, Uganda

Location

Related Publications (2)

• 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.

  PMID: 30687792 DERIVED

• 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.

  PMID: 28472067 DERIVED

MeSH Terms

Conditions

Tuberculosis; Schistosomiasis

Interventions

MVA 85A

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Trematode Infections; Helminthiasis; Parasitic Diseases; Vector Borne Diseases

Study Officials

• Helen McShane

  University of Oxford

  STUDY DIRECTOR

• Alison Elliot

  MRC/UVRI and LSHTM Uganda Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 3, 2014
• First Posted: July 1, 2014
• Study Start: June 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: January 30, 2015

Record last verified: 2015-01

Locations

UG (1)