Trial Outcomes & Findings for Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents (NCT NCT02378207)

Last Updated: 2019-11-18

Results Overview

The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

84 participants

Primary outcome timeframe

Up to 8 months

Results posted on

2019-11-18

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1 H4:IC31 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 2 H56:IC31 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 3 BCG (2-8 x 105 CFU) Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Group 4 Control Sodium Chloride 0.9% Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Overall Study STARTED	24	24	24	12
Overall Study COMPLETED	24	21	22	11
Overall Study NOT COMPLETED	0	3	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1 H4:IC31 n=24 Participants 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	Group 2 H56:IC31 n=24 Participants 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	Group 3 BCG (2-8 x 105 CFU) n=24 Participants Administered ID as 0.1 mL in either deltoid muscle at Day 0. n=24	Group 4 Control Sodium Chloride 0.9% n=12 Participants Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. n=24	Total n=84 Participants Total of all reporting groups
Age, Categorical <=18 years	24 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	12 Participants n=4 Participants	84 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	13.8 years STANDARD_DEVIATION 1.42 • n=5 Participants	13.7 years STANDARD_DEVIATION 1.46 • n=7 Participants	14.5 years STANDARD_DEVIATION 1.47 • n=5 Participants	13.2 years STANDARD_DEVIATION 1.11 • n=4 Participants	13.9 years STANDARD_DEVIATION 1.45 • n=21 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	13 Participants n=7 Participants	11 Participants n=5 Participants	6 Participants n=4 Participants	45 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	6 Participants n=4 Participants	39 Participants n=21 Participants
Region of Enrollment South Africa	24 participants n=5 Participants	24 participants n=7 Participants	24 participants n=5 Participants	12 participants n=4 Participants	84 participants n=21 Participants
Participants: QuantiFERON-TB Gold In-Tube (QFT-GIT)-negative, HIV-negative, and BCG vaccinated	24 Participants n=5 Participants	24 Participants n=7 Participants	24 Participants n=5 Participants	12 Participants n=4 Participants	84 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 8 months

The number of solicited and unsolicited adverse events (AEs), including serious adverse events (SAEs), recorded post-vaccination for all participants.

Outcome measures

Outcome measures
Measure	Group 1 H4:IC31 n=24 Participants 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 2 H56:IC31 n=24 Participants 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 3 BCG (2-8 x 105 CFU) n=24 Participants Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Group 4 Control Sodium Chloride 0.9% n=12 Participants Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Number of Participants With Adverse Events	22 participants	20 participants	24 participants	10 participants

PRIMARY outcome

Timeframe: Days 70 and 168

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.

Outcome measures

Outcome measures
Measure	Group 1 H4:IC31 n=24 Participants 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 2 H56:IC31 n=24 Participants 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.	Group 3 BCG (2-8 x 105 CFU) n=24 Participants Administered ID as 0.1 mL in either deltoid muscle at Day 0.	Group 4 Control Sodium Chloride 0.9% n=12 Participants Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56.
Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline Response rates to Ag85B on Day 70	40.0 percentage of participants Interval 21.9 to 61.3	45.0 percentage of participants Interval 25.8 to 65.8	0.0 percentage of participants Interval 0.0 to 17.6	0.0 percentage of participants Interval 0.0 to 25.95
Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline Response rates to TB10.4 on Day 70	21.1 percentage of participants Interval 8.5 to 43.3	5.6 percentage of participants Interval 1.0 to 25.8	5.9 percentage of participants Interval 1.0 to 27.0	0.0 percentage of participants Interval 0.0 to 25.9
Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline Response rates to Ag85B on Day 168	21.7 percentage of participants Interval 9.7 to 41.9	9.5 percentage of participants Interval 2.7 to 28.9	4.3 percentage of participants Interval 0.8 to 21.0	0.0 percentage of participants Interval 0.0 to 27.8
Percentage of Participants With Response Rates to TB Antigens as Compared to Baseline Response rate to TB10.4 on Day 168	8.7 percentage of participants Interval 2.4 to 26.8	0.0 percentage of participants Interval 0.0 to 15.5	0.0 percentage of participants Interval 0.0 to 14.3	0.0 percentage of participants Interval 0.0 to 27.8

SECONDARY outcome

Timeframe: Up to day 168.

Vaccine-specific binding antibodies elicited by the vaccine regimens as determined by multiplex antibody assay and/or enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to day 168

* 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..

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to day 168

Blood concentrations of innate immune cell populations including lymphocyte populations, dendritic cells, monocytes, and granulocytes before and after vaccination

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to day 168

* 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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to day 168

* 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.

Outcome measures

Outcome data not reported

Adverse Events

Group 1 H4:IC31

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Group 2 H56:IC31

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Group 3 BCG (2-8 x 105 CFU)

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Group 4 Control Sodium Chloride 0.9%

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1 H4:IC31 n=24 participants at risk 15 mcg H4/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. H4:IC31	Group 2 H56:IC31 n=24 participants at risk 5 mcg H56/500 nmol IC31 administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. H56:IC31	Group 3 BCG (2-8 x 105 CFU) n=24 participants at risk Administered ID as 0.1 mL in either deltoid muscle at Day 0. BCG	Group 4 Control Sodium Chloride 0.9% n=12 participants at risk Administered IM as 0.5 mL in alternating deltoid muscle at Days 0 and 56. Control Sodium Chloride 0.9%
Infections and infestations Impetigo	0.00% 0/24 • 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	4.2% 1/24 • Number of events 1 • 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	0.00% 0/24 • 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	0.00% 0/12 • 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
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/24 • 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	0.00% 0/24 • 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	4.2% 1/24 • Number of events 1 • 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	0.00% 0/12 • 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
Investigations Cardiac murmur functional	0.00% 0/24 • 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	4.2% 1/24 • Number of events 1 • 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	0.00% 0/24 • 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	0.00% 0/12 • 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

Other adverse events

Additional Information

Dr. Linda-Gail Bekker

Desmond Tutu HIV Foundation, Cape Town, South Africa

Phone: +27214066959

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place