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.: PACTR201704002006214 Date of Approval: 30/01/2017
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A-043 Phase II study to Evaluate Safety, Immunogencity and Prevention of Infection with Mtb of H56:IC31 in Healthy Adolescents
Official scientific title A Randomized, Placebo Controlled, Double-Blind Phase II Study to Evaluate Safety, Immunogencitiy and Prevention of Infection with Mycobacterium tuberculosis (Mtb) of H56:IC31 in Healthy Adolescents
Brief summary describing the background and objectives of the trial Primary Objectives - To evaluate the safety profile of H56:IC31 compared to placebo in HIV-uninfected, remotely BCG vaccinated adolescents. - To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of conversion using an ESAT-6 free IGRA. Primary Outcome Measure (Safety) - Frequency and severity of adverse events Primary Outcome Measure (Efficacy) - ESAT-6 free IGRA conversion from a negative to positive test at any time point after Day 84 and through end of follow-up for the primary endpoint. Secondary Objectives - To evaluate prevention of Mtb infection by H56:IC31 compared to placebo, as measured by rates of sustained conversion using an ESAT-6 free IGRA. - To evaluate trends in ESAT-6 free IGRA prolonged/sustained conversions and late reversions (i.e., through more than 6 months post initial conversion) in ESAT-6 free IGRA converters. - To investigate the immunogenicity of H56:IC31 in HIV-uninfected, remotely BCG vaccinated adolescents. Secondary Outcome Measures (Efficacy) - Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after Day 84 and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. - Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after randomization and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. - Initial ESAT-6 free IGRA reversion from a positive to a negative test at any time point after primary ESAT-6 free IGRA conversion through the end of follow up.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) A 043
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 30/06/2017
Actual trial start date
Anticipated date of last follow up 05/05/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 1400
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
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 random numbers generated by IWRS; stratified by site Central randomization by phone/internet 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 H56:IC31 0.5 ml, Days 0 and 56 Up to 30 months follow-up 700
Control Group Placebo 0.5 ml; Study days 0 and 56 Follow-up up to 30 months 0.9% sterile saline 700 Placebo
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 as necessary, and has no current plans to move from the study area for the duration of the study 4. For female participants: agrees to avoid pregnancy from 21 days prior to Study Day 0 through 6 months after the last study vaccination. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, or intrauterine device (IUD) 5. Has general good health, confirmed by medical history and physical examination 6. Had BCG vaccination at least 5 years ago documented by confirmation of parent/guardian that the participant received all childhood vaccines or by presence of healed BCG scar 7. Tests ESAT-6 free IGRA and QFT-Plus negative at screening, using a pre-determined threshold for ESAT-6 free IGRA and the manufacturer¿s recommended threshold for QFT-Plus of 0.35 IU/mL in either of the TB antigen tubes after nil-subtraction 1.Acute illness on Study Day 0 2.Axillary temperature <37.5 C on Study Day 0 3.Abnormal laboratory values from the most recent blood collected prior to randomization as follows (abnormal results may be repeated once and if found to be resolved the participant will not be excluded): 4.Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator 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 investigational product 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 household with an individual receiving anti-TB treatment, or known to have incompletely treated culture or smear positive TB, at screening 9.History of autoimmune disease or immunosuppression 10.Used immunosuppressive medication within 42 days before Study Day 0 (inhaled and topical corticosteroids are permitted) 11.Received immunoglobulin or blood products within 42 days before Study Day 0 12.Received any investigational drug or investigational vaccine within 180 days before Study Day 0, or planned participation in any other clinical trial during the study period 13.Received investigational TB vaccine at any time prior to Study Day 0 14.Administration of a licensed vaccine in the period starting 28 days before and ending 28 days after each dose of investigational product 15.History or laboratory evidence of any past or present possible immunodeficiency state. 16.History of allergic disease or reactions. 17.History of alcohol or drug abuse 18.Any female currently pregnant or lactating/nursing, or positive urine pregnancy test 19.Received a tuberculin skin test (TST) within 3 months (90 days) prior to Study day 0 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
No 07/02/2017 University of Witwatersrand Ethics Committee
Ethics Committee Address
Street address City Postal code Country
1 Jan Smuts Avenue, Braamfontein Johannesburg 2000 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Frequency and severity of Adverse Events Day 0 thru Month 30
Primary Outcome ESAT-6 free IGRA conversion from a negative to a positive test after day 84 Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome ¿ Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after Day 84 and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. Day 84 Month 6 Month 12 Month 18 Month 24
Primary Outcome Frequency and severity of Adverse Events Day 0 thru Month 30
Primary Outcome ESAT-6 free IGRA conversion from a negative to a positive test after day 84 Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome ¿ Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after Day 84 and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after randomization and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. Day 84 Month 6 Month 12 Month 18 Month 24
Primary Outcome Frequency and severity of Adverse Events Day 0 thru Month 30
Primary Outcome ESAT-6 free IGRA conversion from a negative to a positive test after day 84 Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after randomization and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome Primary ESAT-6 free IGRA conversion from a negative to a positive test at any time point after Day 84 and through end of follow up for the primary endpoint, AND persisting without ESAT-6 free IGRA reversion from a positive to a negative test through 6 months after ESAT-6 free IGRA conversion. Day 84 Month 6 Month 12 Month 18 Month 24
Secondary Outcome Initial ESAT-6 free IGRA reversion from a positive to a negative test at any time point after primary ESAT-6 free IGRA conversion through the end of follow up. Day 84 Month 6 Month 12 Month 18 Month 24
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Mwanza Research Centre - The National Institute for Medical Research (NIMR) 3 Barack Obama Drive P.O. Box 9653 Dar es Salaam 11101 Tanzania
The Aurum Institute - Rustenburg Clinical Research Centre 1st Floor, 50 Steen Street Rustenburg 0300 South Africa
The Aurum Institute - Tembisa Clinical Research Centre Hospital View Tembisa 1632 South Africa
The Aurum Institute - Klerksdorp Clinical Research Centre 2nd Floor, Room 201 Jade Square Klerksdorp 2571 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust 215 Euston Rd London NW12BE United Kingdom
GLOBVAC PO Box 564 Lysaker N-1327 Norway
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Aeras 1405 Research Blvd Rockville, Maryland 20850 United States of America Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
None
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Dereck Tait dtait@aeras.org 27 021 442 4991 Black River Park, First Floor, Old Warehouse Building,
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Sr. Director Clinical Development/Aeras
Role Name Email Phone Street address
Public Enquiries Dereck Tait dtait@aeras.org 27 021 442 4991 Black River Park, First Floor, Old Warehouse Building,
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Sr. Director Clinical Development/Aeras
Role Name Email Phone Street address
Scientific Enquiries Dereck Tait dtait@aeras.org 27 021 442 4991 Black River Park, First Floor, Old Warehouse Building, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Sr. Director Clinical Development/Aeras
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information