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

Tuberculosis Clinical Trial

— TB036  

Official title:

A Phase II Open Label Trial to Investigate the Effect of Schistosoma Mansoni (Sm) Infection on the Immunogenicity of a Candidate TB Vaccine, MVA85A, in BCG-vaccinated African Adolescents

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02178748
• Other study ID #: TB036
• Status: Completed
• Phase: Phase 2
• First received: June 3, 2014
• Last updated: January 29, 2015
• Start date: June 2014
• Est. completion date: January 2015

Study information

• Verified date: January 2015
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Health authority: Uganda: National Drug Authority
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Years to 17 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Schistosomiasis
• Schistosomiasis mansoni
• Tuberculosis

Intervention

Biological:
• MVA85A
Single dose of 1x10^8pfu MVA85A intramuscular vaccination

Locations

Country	Name	City	State
Uganda	MRC/UVRI Uganda Research Unit on AIDS	Entebbe

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	MRC/UVRI Uganda Research Unit on Aids

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Actively and passively collected data on adverse events.	To assess the safety of MVA85A vaccination in BCG-vaccinated African adolescents aged 12-17 years.	8 weeks	Yes
Primary	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	No
Secondary	Evaluation of cytokines in supernatant of stimulated cells using Luminex and flow cytometry of Ag85A response.	Effects of S. mansoni infection on other aspects of the immune response following MVA85A immunisation.	8 weeks	No