Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201512001069358 Date of Approval: 12/03/2015
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Phase II Study of H4:IC31 and BCG revaccination in Healthy Adolescents (040-404)
Official scientific title A Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents
Brief summary describing the background and objectives of the trial This Phase II, randomized, 3-arm, placebo controlled, partially blinded, clinical trial will be conducted in 990 healthy, HIV-uninfected, QFT-GIT negative, previously BCG vaccinated adolescents. Primary Outcome Measure: 1. Safety, in HIV-uninfected, remotely BCG vaccinated adolescents, of H4:IC31 (AERAS 404)or BCG revaccination; measured by the number and percentage of unsolicited and solicited adverse events recorded post vaccination. 2. Prevention of Mtb infection, as measured by rates of conversion using a QFT-GIT assay (change from negative to positive), by AERAS-404 compared to placebo or BCG revaccination compared to placebo.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) C 040 404
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Prevention
Anticipated trial start date 18/02/2014
Actual trial start date 18/02/2014
Anticipated date of last follow up 26/09/2017
Actual Last follow-up date 28/08/2017
Anticipated target sample size (number of participants) 990
Actual target sample size (number of participants) 990
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Randomly-generated sequence of subject identification numbers (randomization schedule) managed by a validated IVRS/IWRS. Randomization will be in blocks for each school or community, as the epidemiology of TB transmission may vary from one school or community to another. Central randomization by a validated IVRS/IWRS Masking/blinding used
Parallel: different groups receive different interventions at same time during study Randomised Randomly-generated sequence of subject identification numbers (randomization schedule) managed by a validated IVRS/IWRS. Randomization will be in blocks for each school or community, as the epidemiology of TB transmission may vary from one school or community to another. Central randomization by a validated IVRS/IWRS Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group AERAS-404 15 mcgH4/500 nmol IC31; 2 doses day 0 and 56 Vaccinate on days 0 and 56; followed for up to 30 months. The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as ¿-antigen and is a 30-kDa mycolyl transferase protein. 330
Experimental Group Bacillus Calmette-Guérin (BCG) One dose on day 0; (0.1 mL) contains 2 to 8 x 105 CFU Vaccinate on day 0 and follow for up to 30 months. BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. BCG SSI is supplied by the manu 330
Control Group Placebo 0.5mL days 0 and 56 Vaccinate on days 0 and 56; Follow up for up to 30 months Saline 330 Placebo
Experimental Group Bacillus Calmette-Guérin (BCG) One dose on day 0; (0.1 mL) contains 2 to 8 x 105 CFU Vaccinate on day 0 and follow for up to 30 months. BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. 330 Active-Treatment of Control Group
Experimental Group AERAS-404 15 mcgH4/500 nmol IC31; 2 doses day 0 and 56 Vaccinate on days 0 and 56; followed for up to 30 months. The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as alpha-antigen and is a 30-kDa mycolyl transferase protein. 330 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1.Has completed the written informed consent and assent process 2.Is age ¿ 12 years and ¿ 17 years on Study Day 0 3.Agrees to stay in contact with the study site for the duration of the study, provide updated contact information 4.For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and for the full duration of the study. 5.Has general good health, confirmed by medical history and physical examination 6.Has body mass index (BMI) for age and sex between the 5th and 95th centiles by Centers for Disease Control nomogram 7.Had BCG vaccination at least 5 years ago documented through medical history or by presence of healed BCG scar 8.Tests QFT-GIT negative at screening, using the manufacturer's recommended threshold of 0.35 IU/mL 1.Acute illness on Study Day 0 2.Oral temperature <=37.5°C on Study Day 0 3.Clinically significant (and no more than Grade 1 on the Toxicity Scale) abnormal laboratory values from blood collected within 21 days 4.Evidence of clinically significant (and no more than Grade 1 on the Toxicity Scale) systemic or local disease on urinalysis 5.History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of study vaccine in the opinion of the investigator 6.History of treatment for active TB disease or latent Mtb infection 7.History or evidence, including chest X-ray, of active TB disease 8.Shared residence with an individual receiving anti-TB treatment, or known incompletely treated culture or smear positive TB 9.History of autoimmune disease or immunosuppression 10.Used immunosuppressive medication within 42 days before Study Day 0 11.Received immunoglobulin or blood products within 42 days before Study Day 0 12.Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0 13.Received investigational TB vaccine, other than BCG 14.Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after each dose of study vaccine 15.History or laboratory evidence of any past or present possible immunodeficiency state not limited to any lab indication of HIV-1 infection 16.History of allergic disease likely to be exacerbated by any component of the study vaccine 17.History of alcohol or drug abuse 18.All female subjects: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening 19.Received a (TST) within 3 months (90 days) prior to Study Day 0. 20.Any current medical, psychiatric, occupational, substance abuse problems problems that in opinion of investigator will make unlikely for the subject to comply with the protocol 12 Year(s) 17 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 02/10/2013 UCT
Ethics Committee Address
Street address City Postal code Country
Old Main Building, Groote Schuur Hospital Observatory 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety, in HIV-uninfected, remotely BCG vaccinated adolescents, of Aeras-404 or BCG revaccination; measured by the number and percentage of unsolicited and solicited adverse events recorded post vaccination. SAEs and SUSARS throughout the study.
Primary Outcome Prevention of Mtb infection, as measured by rates of conversion using a QFT-GIT assay (change from negative to positive), by AERAS-404 compared to placebo or BCG revaccination compared to placebo. Every 6 months while on study
Secondary Outcome Prevention of Mtb infection measured by rates of sustained conversion using a QFT-GIT assay, by AERAS-404 compared to placebo, or BCG revaccination compared to placebo. Every 3 months up to 6 months post-conversion
Secondary Outcome immunogenicity in HIV-uninfected, remotely BCG vaccinated adolescents of of AERAS-404 or BCG. Every 6 months until conversion
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Desmond Tutu HIV Foundation-Emavundleni 14 Sonwabile Drive Nyanga 7750 South Africa
SATVI Brewelskloof Hospital, Harlem Street Worcester, Cape Town, Western Cape 6850 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Aeras 1405 Research Blvd Rockville 20850 United States of America
Sanofi Pasteur Discovery Drive Swiftwater 18370 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Aeras 1405 Research Blvd Rockville 20850 United States of America Commercial Sector/Industry
Secondary Sponsor Sanofi Pasteur Commercial Sector/Industry
Secondary Sponsor NIH Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Sanofi Pasteur Discovery Drive Swiftwater 18370 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mark Hatherill Mark.Hatherill@uct.ac.za 27 21 404 7618 Haarlem Street
City Postal code Country Position/Affiliation
Worcester 6850 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Robert Hopkins rhopkins@aeras.org 301-547-2922 1405 Research Blvd
City Postal code Country Position/Affiliation
Rockville 20850 United States of America Product Director
Role Name Email Phone Street address
Scientific Enquiries Robert Hopkins rhopkins@aeras.org 301-547-2922 1405 Research Blvd.
City Postal code Country Position/Affiliation
Rockville 20850 United States of America Product Director
REPORTING
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