A Study of MVA85A in Healthy Infants

NCT ID: NCT00953927

Last Updated: 2016-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2797 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31

Brief Summary

This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in Bacillus Calmette-Guérin (BCG) vaccinated infants without tuberculosis or HIV infection. This study planned to enroll 2784 infants (126 to 182 days of age) who received study vaccine or control and were followed for 15 - 36 months. The study was conducted at a single site in South Africa.

Detailed Description

This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in BCG vaccinated infants without tuberculosis or HIV infection. Infants (126 to 182 days) received intradermal (ID) study vaccine (MVA85A/AERAS-485 or Candida skin test antigen control). All infants were to be followed for at least 15 months after the last infant was enrolled into the study. Given completion of enrollment in 21 months, the total duration of follow-up for each infant was scheduled to be at least 15 months and up to 36 months. Infants were to be followed for the entire duration of the study both for the development of tuberculosis and serious adverse events.

On enrollment to the study, eligible infants were assigned to a study group starting with Study Group 1 and were randomized in a 1:1 ratio within a study group to receive either MVA85A/AERAS-485 or Candida skin test antigen control. Infants were assigned to a safety cohort (Study Group 1), then into 1 of 3 immunological assay evaluation groups (Study Groups 2-4), and finally the remainder of infants were assigned into the correlate of protection cohort (Study Group 5). At least 330 infants were to be randomized in Study Group 1, up to 50-60 infants each in Study Groups 2-4, and the remaining infants were randomized in Study Group 5.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Investigational Vaccine

MVA85A/AERAS-485; subset into cohorts to explore different safety and immunogenicity tests.

Group Type: EXPERIMENTAL

MVA85A/AERAS-485

Intervention Type: BIOLOGICAL

Attenuated virus MVA vector with insertion. Single dose vaccine, 1 x 10\^8 pfu.

Control Group

Candida Skin Test Antigen control; subset into cohorts to explore different safety and immunogenicity tests.

Group Type: PLACEBO_COMPARATOR

Candida Skin Test Antigen

Intervention Type: BIOLOGICAL

1 test, administered once as a placebo control.

Interventions

MVA85A/AERAS-485

Attenuated virus MVA vector with insertion. Single dose vaccine, 1 x 10\^8 pfu.

Intervention Type: BIOLOGICAL

Candida Skin Test Antigen

1 test, administered once as a placebo control.

Intervention Type: BIOLOGICAL

Other Intervention Names

Manufactured by IDT of Germany.; Candin(R); Manufactured by Allermed Laboratories of USA.

Eligibility Criteria

Inclusion Criteria

1. Age of 126 through 182 days on the day of randomization (Study Day 0)

2. Written informed consent obtained from the parents/guardian

3. Weight: by chart >3rd percentile on Study Day 0 or, if < 3rd percentile, infant has shown a stable growth pattern

4. BCG vaccination within 7 days of birth

5. Generally good health confirmed by medical history and physical examination within 35 days prior to Study Day 0

6. Must have received age-appropriate doses of pneumococcal vaccine as recommended by the South African Department of Health but no injection within 14 day prior to Study Day 0

7. Ability to complete follow-up period as required by the protocol

8. Completed simultaneous enrollment in the Aeras Vaccine Development Registry protocol

Exclusion Criteria

1. Acute illness on Study Day 0

2. Fever >=37.5 degrees Celsius on Study Day 0

3. Evidence of significant active infection on Study Day 0

4. Received a Expanded Program of Immunization (EPI) within 14 days prior to Study Day 0

5. Historical or virological evidence of individual or maternal human immunodeficiency virus (HIV-1) infection

6. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine

7. Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the infant in the study

8. Evidence of chronic hepatitis from any cause

9. 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

10. History of or known tuberculosis or treatment for tuberculosis

11. Shared residence since birth with an individual with active tuberculosis or on anti-tuberculosis treatment for less than 2 months

• Minimum Eligible Age: 126 Days
• Maximum Eligible Age: 182 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Oxford

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

Aeras

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michele Tameris, MD

Role: PRINCIPAL_INVESTIGATOR

South African Tuberculosis Vaccine Initiative

Bernard Landry, MPH

Role: STUDY_DIRECTOR

Aeras

Helen McShane, MD

Role: STUDY_CHAIR

University of Oxford; Centre for Vaccinology & Tropical Medicine

Locations

South African Tuberculosis Vaccine Initiative (Satellite)

Ceres, , South Africa

South African Tuberculosis Vaccine Initiative (Satellite)

Robertson, , South Africa

South African Tuberculosis Vaccine Initiative (Headquarters)

Worcester, , South Africa

Countries

South Africa

References

Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, Shea JE, McClain JB, Hussey GD, Hanekom WA, Mahomed H, McShane H; MVA85A 020 Trial Study Team. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013 Mar 23;381(9871):1021-8. doi: 10.1016/S0140-6736(13)60177-4.

Reference Type: BACKGROUND

PMID: 23391465 (View on PubMed)

Tameris M, McShane H, McClain JB, Landry B, Lockhart S, Luabeya AK, Geldenhuys H, Shea J, Hussey G, van der Merwe L, de Kock M, Scriba T, Walker R, Hanekom W, Hatherill M, Mahomed H. Lessons learnt from the first efficacy trial of a new infant tuberculosis vaccine since BCG. Tuberculosis (Edinb). 2013 Mar;93(2):143-9. doi: 10.1016/j.tube.2013.01.003. Epub 2013 Feb 12.

Reference Type: BACKGROUND

PMID: 23410889 (View on PubMed)

Mulenga H, Tameris MD, Luabeya KK, Geldenhuys H, Scriba TJ, Hussey GD, Mahomed H, Landry BS, Hanekom WA, McShane H, Hatherill M. The Role of Clinical Symptoms in the Diagnosis of Intrathoracic Tuberculosis in Young Children. Pediatr Infect Dis J. 2015 Nov;34(11):1157-62. doi: 10.1097/INF.0000000000000847.

Reference Type: BACKGROUND

PMID: 26226446 (View on PubMed)

Luabeya KK, Tameris MD, Geldenhuys HD, Mulenga H, Van Schalkwyk A, Hughes EJ, Toefey A, Scriba TJ, Hussey G, Mahomed H, McShane H, Landry B, Hanekom WA, Hatherill M. Risk of Disease After Isoniazid Preventive Therapy for Mycobacterium tuberculosis Exposure in Young HIV-uninfected Children. Pediatr Infect Dis J. 2015 Nov;34(11):1218-22. doi: 10.1097/INF.0000000000000874.

Reference Type: BACKGROUND

PMID: 26252568 (View on PubMed)

Muller J, Tanner R, Matsumiya M, Snowden MA, Landry B, Satti I, Harris SA, O'Shea MK, Stockdale L, Marsay L, Chomka A, Harrington-Kandt R, Thomas ZM, Naranbhai V, Stylianou E, Mbandi SK, Hatherill M, Hussey G, Mahomed H, Tameris M, McClain JB, Evans TG, Hanekom WA, Scriba TJ, McShane H, Fletcher HA. Cytomegalovirus infection is a risk factor for tuberculosis disease in infants. JCI Insight. 2019 Dec 5;4(23):e130090. doi: 10.1172/jci.insight.130090.

Reference Type: DERIVED

PMID: 31697647 (View on PubMed)

Bunyasi EW, Tameris M, Geldenhuys H, Schmidt BM, Luabeya AK, Mulenga H, Scriba TJ, Hanekom WA, Mahomed H, McShane H, Hatherill M. Evaluation of Xpert(R) MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial. PLoS One. 2015 Nov 10;10(11):e0141623. doi: 10.1371/journal.pone.0141623. eCollection 2015.

Reference Type: DERIVED

PMID: 26554383 (View on PubMed)

Matsumiya M, Harris SA, Satti I, Stockdale L, Tanner R, O'Shea MK, Tameris M, Mahomed H, Hatherill M, Scriba TJ, Hanekom WA, McShane H, Fletcher HA. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infect Dis. 2014 Jun 9;14:314. doi: 10.1186/1471-2334-14-314.

Reference Type: DERIVED

PMID: 24912498 (View on PubMed)

Other Identifiers

Oxford TB020

Identifier Type: OTHER

Identifier Source: secondary_id

C-020-485

Identifier Type: -

Identifier Source: org_study_id