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.: PACTR201808711101850 Date of Approval: 29/08/2018
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of H56:IC31 in Reducing the rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis
Official scientific title A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of H56:IC31 in Reducing the rate of TB Disease Recurrence in HIV Negative Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis
Brief summary describing the background and objectives of the trial To evaluate the following in HIV-negative participants who have completed at least 5 months (22 weeks) treatment for drug-susceptible pulmonary TB and who test negative for acid fast bacilli (AFB) on sputum smear microscopy prior to vaccination (participants unable to produce sputum, and considered asymptomatic by the investigator, may be considered Mtb negative): • Efficacy of H56:IC31 compared to placebo in reducing the rate of recurrent TB disease (relapse or reinfection)
Type of trial RCT
Acronym (If the trial has an acronym then please provide) A055 POR
Disease(s) or condition(s) being studied Infections and Infestations,Respiratory
Sub-Disease(s) or condition(s) being studied Tuberculosis
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/04/2019
Actual trial start date 31/01/2019
Anticipated date of last follow up 30/03/2023
Actual Last follow-up date 20/03/2023
Anticipated target sample size (number of participants) 900
Actual target sample size (number of participants) 831
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 Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Placebo Intramuscular administration on Days 0 and 56 Two intramuscular administrations 0.9 % saline 450 Placebo
Experimental Group H56IC31 5 g H56 / 500 nmol IC31 Intramuscular administrations on Days 0 and 56 Two intramuscular injections The H56:IC31 vaccine candidate consists of a fusion protein (H56) of three antigens expressed at different stages of Mycobacterium tuberculosis (Mtb) infection (Ag85B, ESAT-6, Rv2660c) and the IC31 adjuvant. 450
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Completed the written informed consent process. 2. Agrees to give access to medical records for study related purposes. 3. HIV-negative (self-reported) with a diagnosis of drug susceptible pulmonary TB at the start of the TB treatment. 4. Able to provide 2 separate sputum samples within ≤ 7 days of starting TB treatment. Participants are not expected to provide sputum samples prior to starting TB treatment if their 1st screening visit (V1) is performed on the same day as their 2nd screening visit (V2). 5. Tested Mtb negative by smear AFB microscopy of 2 separate sputum samples taken on V2. Participants unable to produce sputum, but considered asymptomatic by the investigator, may be considered Mtb negative and eligible for inclusion. 6. Confirmed HIV negative on V2. 7. Completed ≥ 5 months (22 weeks) of TB treatment with treatment still ongoing at the time of the 1st vaccination on V3= Day 0, and total treatment time not extended beyond 28 weeks. 8. Aged ≥ 18 years on the date of V1 and ≤ 60 years on the date of V3= Day 0. 9. 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 area for the duration of the study. 1. Diagnosis or co-diagnosis of extra pulmonary TB. 2. Hospitalized for the current episode of drug susceptible pulmonary TB disease. 3. History of receipt of treatment against active TB, prior to the current treatment episode, within the last 5 years. 4. History of or ongoing severe disease that in the opinion of the investigator might affect the safety of the participant or the immunogenicity of the investigational product. 5. Insulin dependent diabetes. 6. History of allergic disease or reactions likely to be exacerbated by any component of the investigational product. 7. History or laboratory evidence of immunodeficiency, autoimmune disease or immunosuppression. 8. History of chronic hepatitis. 9. Severe anemia, defined as hemoglobin less than 10 g/dL or a hematocrit less than 30 % based on most recent hematology obtained before randomization. 10. Receipt of any investigational TB vaccine previously. 11. Receipt or planned receipt of any investigational drug or investigational vaccine from V1 through V8= Day 421. 12. Receipt or planned receipt of any licensed vaccine from V1 through V6= Day 70, except for SARS-Cov-2 vaccines recommended by national vaccination programs which will be allowed if given > 28 days before and from the time of administration of clinical trial product. 13. Receipt of treatment likely to modify the immune response (e.g. blood products, immunoglobulins, immunosuppressive treatment) within 42 days before V3= Day 0 through V6= Day 70. Inhaled and topical corticosteroids are permitted. 14. Has a body mass index (BMI) < 13 (weight, kg / height, m2) on the date of V1. 15. Female participants of childbearing potential (not sterilized, menstruating or within 1 year of last menses, if post-menopausal): if not willing to use an acceptable method to avoid pregnancy (sterile sexual partner, sexual abstinence, hormonal contraceptives (oral, injection, transdermal patch, or implant) or intrauterine device from 28 days before V3= Day 0 until 2 months Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 60 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 03/12/2018 National Health Research Ethics Review Committee Mbeya Medical Research Centre
Ethics Committee Address
Street address City Postal code Country
2448 Ocean Road Dar es Salaam 9653 United Republic of Tanzania
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 13/08/2018 Mbeya Medical Research and Ethics Committee Mbeya Medical Research Centre
Ethics Committee Address
Street address City Postal code Country
Hospital Hill Road Mbeya 2410 United Republic of Tanzania
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 23/08/2018 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Floor E53, Room 46, Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7925 South Africa
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 05/09/2018 WITS Health Consortium
Ethics Committee Address
Street address City Postal code Country
8 Blackwood Ave, Parktown Johannesburg 2193 South Africa
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 15/08/2018 Pharma Ethics
Ethics Committee Address
Street address City Postal code Country
123 Amcor Road Lyttlelon Manor 0157 South Africa
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 13/08/2018 Mbeya Medical Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Mbeya Zonal Referral Hospital, Hospital Hill Road, Mbeya, Tanzania, Mbeya 0000 Tanzania
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 29/08/2019 Wits Human Research Ethics Committee Medical
Ethics Committee Address
Street address City Postal code Country
Research Office, Faculty of Health Sciences, Phillip Tobias Building, Offices 301-304, 3rd Floor, Cnr York Road and 29 Princess of Wales Terrace, Parktown, 2193 Johannesburg 2193 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Rate of TB disease recurrence (relapse or reinfection), defined as TB diagnosed by confirmation of Mtb by culture of sputum during the period starting 14 days after the 2nd vaccination (V6= Day 70) and ending 12 months after the 2nd vaccination (V8= Day 421). Day 70 - Day 421
Secondary Outcome • Solicited adverse events and all adverse events occurring the first 14 days after each of the 1st and 2nd vaccinations • Serious adverse events including medically important events occurring after the 1st vaccination through the end of the study Day 0 - Day 421
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
South African Tuberculosis Vaccine Initiative SATVI Project Office, University of Cape Town, Brewelskloof Hospital, Haarlem Street Worcester 6850 South Africa
University of Cape Town Lung Institute George Street, Observatory Cape Town 7705 South Africa
TASK Applied Science Smal St, Boston Cape Town 7530 South Africa
The Aurum Institute Gavin J Churchyard Legacy Centre Klerksdorp Clinical Research Centre 201 Jade Square Centre, Cnr Margaretha Prinsloo and OR Tambo Drive Klerksdorp 2571 South Africa
NIMR Mbeya Medical Research Center Hospital Hill Road Mbeya 2410 United Republic of Tanzania
The Aurum Institute Tembisa Clinical Research Centre cnr Rev RT J Namane and Flint Mazibuko Drive, Hospital View Tembisa 1632 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan 51, HW The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor IAVI South Africa NPC Ground Floor, Collingwood Building, Black River Park, 2 Fir Street Observatory 7925 South Africa Charities/Societies/Foundation
Secondary Sponsor Statens Serum Institute 5 Artillerivej Copenhagen S 2300 Denmark Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
The Aurum Institute 29 Queens Rd, Parktown Johannesburg 2194 South Africa
Ospedale San Raffaele S.r.l. Via Olgettina, 60, 20132, MI Milano 20132 Italy
University of Cape Town Lung Institute Pty Ltd George St, Mowbray Cape Town 7700 South Africa
TASK Foundation NPC M2 Karl Bremer Hospital, Mike Pienaar Boulevard, Bellville Cape Town 7530 South Africa
SATVI University of Cape Town Bremner Building, Lovers Walk, Rondebosch Cape Town 7700 South Africa
NIMR Mbeya Medical Research Centre Hospital Hill rd Mbeya United Republic of Tanzania
Statens Serum Instit Artillerivej 5 Copenhagen S 2300 Denmark
IAVI South Africa NPC Ground Floor, Collingwood Building, Black River Park, 2 Fir Street Observatory 7925 South Africa
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Issa Sabi isabi@nimr-mmrc.org +2552503456 Hospital Hill Road
City Postal code Country Position/Affiliation
Mbeya 2410 United Republic of Tanzania Research Scientist
Role Name Email Phone Street address
Public Enquiries Marisa Russell mrussell@iavi.org +27213441200 Ground Floor, Collingwood Building, Black River Park, 2 Fir Street
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Senior Director Clinical Operations
Role Name Email Phone Street address
Scientific Enquiries Marisa Russell mrussell@iavi.org +27214424980 Ground Floor, Collingwood Building, Black River Park, 2 Fir Street
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Senior Director Clinical Operations
Role Name Email Phone Street address
Principal Investigator Mark Hatherill mark.hatherill@uct.ac.za +27214066791 Bremner Building, Lovers Walk, Rondebosch
City Postal code Country Position/Affiliation
Cape Town 7700 South Africa International PI
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Information will be shared in September 2024 Clinical Study Report Information will be shared in September 2024 Information will be shared in September 2024
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Yes 10/09/2024
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 10/09/2024
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information