First-in-Human Trial of the Novel Tuberculosis Vaccine Candidate, H107e/CAF®10b

NCT ID: NCT06050356

Last Updated: 2025-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-14

Study Completion Date

2026-11-30

Brief Summary

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Tuberculosis (TB) is an infection caused by bacteria passed from one person to another through the air when an infected person for instance coughs, speaks, or sneezes. This study tests the safety and vaccine-induced immune response of a new preventive TB vaccine called H107e/CAF®10b. H107e is a copy of protein parts from the bacterium causing tuberculosis, Mycobacterium tuberculosis, which are also called antigens. CAF®10b is an adjuvant which helps the body discover the antigen. The adjuvant and antigen are mixed together to formulate the final vaccine. The final formulated vaccine enhances the immune system's response against the antigen.

This is a first-in-human study, meaning this vaccine is being given to people for the first time. The primary objective is to evaluate the safety of the vaccine and its components; however, the study will also evaluate the specific immune responses generated by the new vaccine. The study is divided into two parts, phase 1a and phase 1b. Phase 1a investigates unadjuvanted H107e, CAF®10b adjuvant, H107e/CAF®10b vaccine (low adjuvant dose), and H107e/CAF®10b vaccine (full adjuvant dose). The trial products are administered twice intramuscularly. H107e is also administered intranasally in one of the groups on Day 85. Phase 1b investigates H107e/CAF®10b, H107e/CAF®10b+Bacillus Calmette-Guérin (BCG), BCG, and placebo. A placebo is a look-alike substance that contains no active drug. All groups in phase 1b receive H107e intranasally on Day 211.

A preventive TB vaccine such as H107e/CAF®10b should be able to introduce the body's immune system to antigens from Mycobacterium tuberculosis. This will result in memory in the immune system, meaning that when a person gets infected with Mycobacterium tuberculosis, the immune system will recognise and target the bacteria to prevent disease, thereby avoiding the need for antibiotic treatment and/or other treatments and their side effects.

Detailed Description

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Conditions

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Healthy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Phase 1a proceeds as sequential dosing to determine early safety signals (Arms 1, 2, 3, 4a, and 4b).

Phase 1b proceeds as parallel assignment. Participants are randomised to one of four treatment arms (H107e/CAF®10b; H107e/CAF®10b + BCG; BCG; placebo).
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Phase 1a is open label

Phase 1b is double-blind, randomised, and placebo controlled

Study Groups

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Arm 1 (phase 1a)

H107e

Group Type EXPERIMENTAL

H107e

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg unadjuvanted H107e on Day 1 and Day 29

Arm 2 (phase 1a)

CAF®10b

Group Type EXPERIMENTAL

CAF®10b

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of CAF®10b (full adjuvant dose) on Day 1 and Day 29

Arm 3 (phase 1a)

H107e/CAF®10b - low adjuvant dose

Group Type EXPERIMENTAL

H107e/CAF®10b - low adjuvant dose

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (low adjuvant dose) on Day 1 and Day 29

Arm 4a (phase 1a)

H107e/CAF®10b - full adjuvant dose - low dose intranasal H107e

Group Type EXPERIMENTAL

H107e/CAF®10b - full adjuvant dose

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

Low dose intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 15 µg H107e (low dose intranasal H107e) on Day 85

Arm 4b (phase 1a)

H107e/CAF®10b - full adjuvant dose - full dose intranasal H107e

Group Type EXPERIMENTAL

H107e/CAF®10b - full adjuvant dose

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

Full dose intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 85

Arm 1 (phase 1b)

H107e/CAF®10b

Group Type EXPERIMENTAL

H107e/CAF®10b

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

i.d. placebo

Intervention Type BIOLOGICAL

Participants will receive one i.d. injection of placebo on Day 1

Intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Arm 2 (phase 1b)

H107e/CAF®10b + BCG

Group Type EXPERIMENTAL

H107e/CAF®10b

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

BCG

Intervention Type BIOLOGICAL

Participants will receive one i.d. injection of BCG on Day 1

Intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Arm 3 (phase 1b)

BCG

Group Type ACTIVE_COMPARATOR

i.m. placebo

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of placebo on Day 1 and Day 29

BCG

Intervention Type BIOLOGICAL

Participants will receive one i.d. injection of BCG on Day 1

Intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Arm 4 (phase 1b)

Placebo

Group Type PLACEBO_COMPARATOR

i.m. placebo

Intervention Type BIOLOGICAL

Participants will receive two i.m. injections of placebo on Day 1 and Day 29

i.d. placebo

Intervention Type BIOLOGICAL

Participants will receive one i.d. injection of placebo on Day 1

Intranasal H107e

Intervention Type BIOLOGICAL

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Interventions

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H107e

Participants will receive two i.m. injections of 20 µg unadjuvanted H107e on Day 1 and Day 29

Intervention Type BIOLOGICAL

CAF®10b

Participants will receive two i.m. injections of CAF®10b (full adjuvant dose) on Day 1 and Day 29

Intervention Type BIOLOGICAL

H107e/CAF®10b - low adjuvant dose

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (low adjuvant dose) on Day 1 and Day 29

Intervention Type BIOLOGICAL

H107e/CAF®10b - full adjuvant dose

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

Intervention Type BIOLOGICAL

Low dose intranasal H107e

Participants will receive one i.n. administration of 15 µg H107e (low dose intranasal H107e) on Day 85

Intervention Type BIOLOGICAL

Full dose intranasal H107e

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 85

Intervention Type BIOLOGICAL

H107e/CAF®10b

Participants will receive two i.m. injections of 20 µg H107e/CAF®10b (full adjuvant dose) on Day 1 and Day 29

Intervention Type BIOLOGICAL

i.m. placebo

Participants will receive two i.m. injections of placebo on Day 1 and Day 29

Intervention Type BIOLOGICAL

BCG

Participants will receive one i.d. injection of BCG on Day 1

Intervention Type BIOLOGICAL

i.d. placebo

Participants will receive one i.d. injection of placebo on Day 1

Intervention Type BIOLOGICAL

Intranasal H107e

Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Healthy adults aged ≥18 years and ≤ 45 years of age on the day of the screening visit
* Completed the written informed consent process
* Confirmed HIV-negative at screening
* Confirmed Xpert MTB/RIF Ultra-negative at screening
* Laboratory values within the indicated ranges obtained at screening:

* Absolute neutrophil count (ANC) ≥800 cells/mm3
* Haemoglobin ≥ 11 g/dL for females and \>10.5 g/dL for males
* Platelet count ≥ 100,000/mm3
* Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
* AST (SGOT), ALT (SGPT), and alkaline phosphatase, ≤ 2.5 X ULN
* Total bilirubin ≤ 2 X ULN)
* Agrees to refrain from blood donation during the course of the trial
* Women of child-bearing potential must use a highly effective form of birth control (confirmed by the investigator) throughout the trial

* A highly effective method of birth control is defined as hormonal contraceptives (oral, injection, transdermal patch, or implant), bilateral tubal occlusion or intrauterine device. The participants must have used the contraceptive method continuously for at least 21 days prior to the pregnancy test at baseline (Day 1)
* A female is defined as not being of child-bearing potential if she is postmenopausal (aged 50 and above with at least 12 months with no menses without an alternative medical cause prior to screening. If less than 50 years old, then confirmatory Follicular stimulating hormone testing is required)
* A female is defined as not being of child-bearing potential if she is surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Written evidence of surgical sterility would be optimal
* Agrees to give access to medical records for trial related purposes
* Agrees to stay in contact with the trial site for the duration of the trial, provide updated contact information as necessary and has no current plans to move from the area for the duration of the trial

Exclusion Criteria

* Previous diagnosis or current diagnosis of TB, including suspected subclinical TB
* Reported current household contact with TB. Note: Daily caregivers to TB infected persons will be considered as household contacts
* 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 trial product
* Insulin-dependent diabetes
* History of allergic disease or reactions likely to be exacerbated by any component of the trial product
* History of chronic allergic rhinitis likely to interfere with the assessment of the mucosal recall
* History of frequent or severe epistaxis
* History or laboratory evidence of primary and/or acquired immunodeficiency, autoimmune disease, or immunosuppression
* History of a malignant condition (e.g. lymphoma, leukaemia, Hodgkin's disease or other tumours of the reticuloendothelial system)
* History of chronic hepatitis
* Has a body mass index ≤18 or ≥35 at screening (weight \[kg\] / (height \[m\] \* height \[m\]))
* Abnormal chest X-ray at screening
* Receipt or planned receipt of any other investigational TB vaccine
* Receipt or planned receipt of any other investigational drug
* Receipt of emergency use authorised/emergency use listed \[EUA/EUL\] vaccines or licensed live attenuated vaccines (e.g., measles, mumps, and rubella \[MMR\], oral polio vaccine \[OPV\], varicella, yellow fever, live attenuated influenza vaccine, live attenuated COVID-19 vaccine) within 30 days prior to screening
* Receipt of any EUA/EUL or licensed vaccines that are not live attenuated vaccines (e.g., tetanus, pneumococcal, Hepatitis A or B, not live attenuated COVID-19 vaccine) within 14 days prior to screening
* Receipt of anticoagulant therapy, including daily acetylsalicylic acid product. NOTE: Intermittent symptomatic use is permitted
* Receipt of treatment likely to modify the immune response (e.g. blood products, immunoglobulins) within 42 days before screening
* Receipt of immunosuppressive medications, including radiotherapy, nasal corticosteroids and inhaled corticosteroids. NOTE: Use of the following is permitted:

* Topical corticosteroids for mild, uncomplicated dermatologic conditions except if administered on the site of injection of trial products
* A single course of oral/parenteral prednisone or equivalent at doses \<60 mg/day and for \<11 days with completion at least 30 days prior to screening
* Female participants: if lactating/nursing, or pregnant as per positive pregnancy test
* Not suitable for inclusion in the opinion of the investigator
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Aurum Institute

OTHER

Sponsor Role collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

South African Tuberculosis Vaccine Initiative

OTHER

Sponsor Role collaborator

Statens Serum Institut

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gavin Churchyard, PhD

Role: STUDY_CHAIR

Aurum Institute

Rasmus Mortensen, PhD

Role: STUDY_CHAIR

Statens Serum Institut

Locations

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Aurum Institute

Pretoria, Gauteng, South Africa

Site Status RECRUITING

Countries

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South Africa

Central Contacts

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Pernille Tingskov

Role: CONTACT

+45 3268 8505

Facility Contacts

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Vaneshree Govender

Role: primary

+27 (0) 10 590 1300

Other Identifiers

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INV-042397

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DOH-27-102023-7355

Identifier Type: REGISTRY

Identifier Source: secondary_id

nTB-01

Identifier Type: -

Identifier Source: org_study_id

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