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Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents

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ClinicalTrials.gov Identifier: NCT02378207
Recruitment Status : Completed
First Posted : March 4, 2015
Results First Posted : November 18, 2019
Last Update Posted : November 18, 2019
Sponsor:
Collaborators:
HIV Vaccine Trials Network
Sanofi Pasteur, a Sanofi Company
Statens Serum Institut
Information provided by (Responsible Party):
Aeras

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Tuberculosis
Interventions Biological: H4:IC31
Biological: H56:IC31
Biological: BCG
Biological: Control Sodium Chloride 0.9%
Enrollment 84
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Hide Arm/Group Description 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. Administered ID as 0.1 mL in either deltoid muscle at Day 0. Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Period Title: Overall Study
Started 24 24 24 12
Completed 24 21 22 11
Not Completed 0 3 2 1
Arm/Group Title Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9% Total
Hide Arm/Group Description

15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

n=24

5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

n=24

Administered ID as 0.1 mL in either deltoid muscle at Day 0.

n=24

Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

n=24

Total of all reporting groups
Overall Number of Baseline Participants 24 24 24 12 84
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 12 participants 84 participants
<=18 years
24
 100.0%
24
 100.0%
24
 100.0%
12
 100.0%
84
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 24 participants 24 participants 12 participants 84 participants
13.8  (1.42) 13.7  (1.46) 14.5  (1.47) 13.2  (1.11) 13.9  (1.45)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 12 participants 84 participants
Female
15
  62.5%
13
  54.2%
11
  45.8%
6
  50.0%
45
  53.6%
Male
9
  37.5%
11
  45.8%
13
  54.2%
6
  50.0%
39
  46.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 24 participants 24 participants 24 participants 12 participants 84 participants
24 24 24 12 84
Participants: QuantiFERON-TB Gold In-Tube (QFT-GIT)-negative, HIV-negative, and BCG vaccinated  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 24 participants 24 participants 12 participants 84 participants
24
 100.0%
24
 100.0%
24
 100.0%
12
 100.0%
84
 100.0%
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.
Time Frame Up to 8 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Hide Arm/Group Description:
15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Administered ID as 0.1 mL in either deltoid muscle at Day 0.
Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Overall Number of Participants Analyzed 24 24 24 12
Measure Type: Number
Unit of Measure: participants
22 20 24 10
2.Primary Outcome
Title Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline
Hide Description Flow cytometry was used to examine TB Mb-specific CD4+ and CD8+ T-cell responses using the ICS assay. The antigens used to stimulate cells in this assay included peptide pools for the vaccine-matched proteins (Ag85B, ESAT-6, Rv2660c, and TB 10.4) as well as complex TB antigens (TB whole cell lysate [TB WCL], and BCG Pasteur strain.
Time Frame Days 70 and 168
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Hide Arm/Group Description:
15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Administered ID as 0.1 mL in either deltoid muscle at Day 0.
Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Overall Number of Participants Analyzed 24 24 24 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Response rates to Ag85B on Day 70
40.0
(21.9 to 61.3)
45.0
(25.8 to 65.8)
0.0
(0.0 to 17.6)
0.0
(0.0 to 25.95)
Response rates to TB10.4 on Day 70
21.1
(8.5 to 43.3)
5.6
(1.0 to 25.8)
5.9
(1.0 to 27.0)
0.0
(0.0 to 25.9)
Response rates to Ag85B on Day 168
21.7
(9.7 to 41.9)
9.5
(2.7 to 28.9)
4.3
(0.8 to 21.0)
0.0
(0.0 to 27.8)
Response rate to TB10.4 on Day 168
8.7
(2.4 to 26.8)
0.0
(0.0 to 15.5)
0.0
(0.0 to 14.3)
0.0
(0.0 to 27.8)
3.Secondary Outcome
Title Evaluate Humoral Responses Elicited by the Different Vaccine Regimens.
Hide Description Vaccine-specific binding antibodies elicited by the vaccine regimens as determined by multiplex antibody assay and/or enzyme-linked immunosorbent assay (ELISA).
Time Frame Up to day 168.
Outcome Measure Data Not Reported
4.Secondary Outcome
Title * Evaluate Immune Response From Vaccine Regimens by Measuring Early (Innate) Vaccine-induced Peripheral Blood Transcription Profiles; Determine Which Responses Are Associated With Antigen-specific Adaptive Responses * Evaluate Adaptive Immune Response.
Hide Description
  • Changes in gene expression measured in longitudinally-collected blood samples relative to samples collected at baseline. The transcriptional profiles will be correlated with antigen-specific adaptive responses measured in Primary objective 2.
  • Transcriptional analysis of antigen-stimulated peripheral blood mononuclear cells (PBMC) at 2 weeks post vaccination will be performed..
Time Frame Up to day 168
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Evaluate Changes in Innate Cells in Response to the Vaccine Regimens
Hide Description Blood concentrations of innate immune cell populations including lymphocyte populations, dendritic cells, monocytes, and granulocytes before and after vaccination
Time Frame Up to day 168
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Measure Non-classical Major Histocompatibility Complex (MHC)-Restricted T-cell Vaccine-induced Responses, Such as to Mycobacterial Lipids (CD1-restricted) and Metabolites (MR1-restricted).
Hide Description
  • Frequency of CD4+, CD8+, and CD4/CD8 double-negative T-cell responses restricted by CD1 (recognizing specific Mtb lipids) before and after BCG revaccination in Group 3 participants.
  • Frequency of mucosal-associated invariant T-cells (MAIT) restricted by MR1 (recognizing vitamin B metabolites) before and after BCG revaccination in Group 3 participants
Time Frame Up to day 168
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Evaluate QFT-GIT and ESAT-6 Free IGRA Discordance and Conversion/Reversion Rate During the Course of the Trial.
Hide Description
  • Magnitude and positivity of interferon (IFN)-γ release using QFT-GIT ELISA in QFT-GIT tests.
  • Magnitude and positivity of IFN-γ release using QFT-GIT ELISA in ESAT-6 free IGRAs.
Time Frame Up to day 168
Outcome Measure Data Not Reported
Time Frame AEs: 7 days post each vaccination Unsolicited AEs: 28 days post each vaccination Solicited injection-site reaction AEs: BCG group - 84 days post each vaccination; H4:IC31/placebo - 28 days post each vaccination; H56:IC31/placebo - 28 days post each vaccination SAEs, AEs of special interest, SUSARs: through day 224
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Hide Arm/Group Description

15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

H4:IC31

5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

H56:IC31

Administered ID as 0.1 mL in either deltoid muscle at Day 0.

BCG

Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.

Control Sodium Chloride 0.9%

All-Cause Mortality
Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/24 (0.00%)      0/24 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      1/24 (4.17%)      1/24 (4.17%)      0/12 (0.00%)    
Infections and infestations         
Impetigo  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Injury, poisoning and procedural complications         
Road traffic accident  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Investigations         
Cardiac murmur functional  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 H4:IC31 Group 2 H56:IC31 Group 3 BCG (2-8 x 105 CFU) Group 4 Control Sodium Chloride 0.9%
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/24 (91.67%)      20/24 (83.33%)      24/24 (100.00%)      10/12 (83.33%)    
Cardiac disorders         
Palpitations  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1
Tachycardia  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/12 (16.67%)  4
Gastrointestinal disorders         
Abdominal pain  1  0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/12 (0.00%)  0
Aphthous stomatitis  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0
Diarrhoea  1  1/24 (4.17%)  1 1/24 (4.17%)  3 6/24 (25.00%)  6 2/12 (16.67%)  2
Nausea  1  3/24 (12.50%)  3 5/24 (20.83%)  7 3/24 (12.50%)  3 1/12 (8.33%)  1
Vomiting  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
General disorders         
Chills  1  5/24 (20.83%)  7 6/24 (25.00%)  7 2/24 (8.33%)  3 2/12 (16.67%)  3
Fatigue  1  6/24 (25.00%)  10 7/24 (29.17%)  12 8/24 (33.33%)  9 1/12 (8.33%)  1
Feeling cold  1  1/24 (4.17%)  1 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Implant site swelling  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Injection site erythema  1  2/24 (8.33%)  3 4/24 (16.67%)  6 0/24 (0.00%)  0 0/12 (0.00%)  0
Injection site pain  1  14/24 (58.33%)  16 13/24 (54.17%)  21 0/24 (0.00%)  0 3/12 (25.00%)  6
Injection site pruritus  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1
Injection site swelling  1  3/24 (12.50%)  4 4/24 (16.67%)  4 0/24 (0.00%)  0 0/12 (0.00%)  0
Pyrexia  1  2/24 (8.33%)  2 2/24 (8.33%)  2 0/24 (0.00%)  0 1/12 (8.33%)  1
Vaccination site discolouration  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Vaccination site erythema  1  0/24 (0.00%)  0 0/24 (0.00%)  0 8/24 (33.33%)  8 0/12 (0.00%)  0
Vaccination site exfoliation  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Vaccination site induration  1  0/24 (0.00%)  0 0/24 (0.00%)  0 10/24 (41.67%)  10 0/12 (0.00%)  0
Vaccination site pain  1  0/24 (0.00%)  0 0/24 (0.00%)  0 14/24 (58.33%)  18 0/12 (0.00%)  0
Vaccination site pruritus  1  0/24 (0.00%)  0 0/24 (0.00%)  0 2/24 (8.33%)  2 0/12 (0.00%)  0
Vaccination site rash  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Vaccination site scab  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Vaccination site scar  1  0/24 (0.00%)  0 0/24 (0.00%)  0 3/24 (12.50%)  3 0/12 (0.00%)  0
Vaccination site swelling  1  0/24 (0.00%)  0 0/24 (0.00%)  0 13/24 (54.17%)  13 0/12 (0.00%)  0
Vaccination site ulcer  1  0/24 (0.00%)  0 0/24 (0.00%)  0 7/24 (29.17%)  7 0/12 (0.00%)  0
Infections and infestations         
Cellulitis  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Folliculitis  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1
Gastroenteritis viral  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Influenza  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Lower respiratory tract infection  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Pharyngitis  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0
Rhinitis  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Trichomoniasis  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0
Upper respiratory tract infection  1  1/24 (4.17%)  1 2/24 (8.33%)  2 0/24 (0.00%)  0 0/12 (0.00%)  0
Vaccination site abscess  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Viral upper respiratory tract infection  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1
Injury, poisoning and procedural complications         
Contusion  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Investigations         
Blood pressure diastolic increased  1  5/24 (20.83%)  7 2/24 (8.33%)  5 4/24 (16.67%)  4 1/12 (8.33%)  1
Blood pressure systolic increased  1  4/24 (16.67%)  4 5/24 (20.83%)  7 4/24 (16.67%)  4 2/12 (16.67%)  2
Neutrophil count decreased  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 1/12 (8.33%)  1
Protein urine  1  5/24 (20.83%)  6 1/24 (4.17%)  1 2/24 (8.33%)  2 2/12 (16.67%)  2
White blood cell count increased  1  0/24 (0.00%)  0 0/24 (0.00%)  0 0/24 (0.00%)  0 2/12 (16.67%)  2
Musculoskeletal and connective tissue disorders         
Arthralgia  1  1/24 (4.17%)  1 3/24 (12.50%)  5 3/24 (12.50%)  4 1/12 (8.33%)  2
Myalgia  1  2/24 (8.33%)  2 5/24 (20.83%)  6 4/24 (16.67%)  4 1/12 (8.33%)  1
Nervous system disorders         
Dizziness  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Headache  1  7/24 (29.17%)  9 6/24 (25.00%)  8 8/24 (33.33%)  8 2/12 (16.67%)  2
Pregnancy, puerperium and perinatal conditions         
Haemorrhage in pregnancy  1  0/24 (0.00%)  0 1/24 (4.17%)  1 0/24 (0.00%)  0 0/12 (0.00%)  0
Renal and urinary disorders         
Haematuria  1  2/24 (8.33%)  2 3/24 (12.50%)  3 0/24 (0.00%)  0 0/12 (0.00%)  0
Proteinuria  1  3/24 (12.50%)  3 2/24 (8.33%)  3 1/24 (4.17%)  1 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Nasal congestion  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders         
Rash  1  1/24 (4.17%)  1 0/24 (0.00%)  0 0/24 (0.00%)  0 0/12 (0.00%)  0
Rash papular  1  0/24 (0.00%)  0 0/24 (0.00%)  0 1/24 (4.17%)  1 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Linda-Gail Bekker
Organization: Desmond Tutu HIV Foundation, Cape Town, South Africa
Phone: +27214066959
EMail: linda-gail.bekker@hiv-research.org.za
Layout table for additonal information
Responsible Party: Aeras
ClinicalTrials.gov Identifier: NCT02378207    
Other Study ID Numbers: HVTN 602 / AERAS A-042
First Submitted: February 12, 2015
First Posted: March 4, 2015
Results First Submitted: September 3, 2019
Results First Posted: November 18, 2019
Last Update Posted: November 18, 2019