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First-in-Human Trial of the Novel Tuberculosis Vaccine Candidate, H107e/CAF®10b (nTB-01)

S

Statens Serum Institut

Status and phase

Enrolling
Phase 1

Conditions

Healthy

Treatments

Biological: H107e/CAF®10b - low adjuvant dose
Biological: i.m. placebo
Biological: Full dose intranasal H107e
Biological: Low dose intranasal H107e
Biological: H107e/CAF®10b - full adjuvant dose
Biological: BCG
Biological: CAF®10b
Biological: Intranasal H107e
Biological: H107e/CAF®10b
Biological: H107e
Biological: i.d. placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT06050356
INV-042397 (Other Grant/Funding Number)
nTB-01
DOH-27-102023-7355 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment

140 estimated patients

Sex

All

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Prevention

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

140 participants in 9 patient groups, including a placebo group

Arm 1 (phase 1a)
Experimental group
Description:
H107e
Treatment:
Biological: H107e
Arm 2 (phase 1a)
Experimental group
Description:
CAF®10b
Treatment:
Biological: CAF®10b
Arm 3 (phase 1a)
Experimental group
Description:
H107e/CAF®10b - low adjuvant dose
Treatment:
Biological: H107e/CAF®10b - low adjuvant dose
Arm 4a (phase 1a)
Experimental group
Description:
H107e/CAF®10b - full adjuvant dose - low dose intranasal H107e
Treatment:
Biological: H107e/CAF®10b - full adjuvant dose
Biological: Low dose intranasal H107e
Arm 4b (phase 1a)
Experimental group
Description:
H107e/CAF®10b - full adjuvant dose - full dose intranasal H107e
Treatment:
Biological: H107e/CAF®10b - full adjuvant dose
Biological: Full dose intranasal H107e
Arm 1 (phase 1b)
Experimental group
Description:
H107e/CAF®10b
Treatment:
Biological: i.d. placebo
Biological: H107e/CAF®10b
Biological: Intranasal H107e
Arm 2 (phase 1b)
Experimental group
Description:
H107e/CAF®10b + BCG
Treatment:
Biological: H107e/CAF®10b
Biological: Intranasal H107e
Biological: BCG
Arm 3 (phase 1b)
Active Comparator group
Description:
BCG
Treatment:
Biological: Intranasal H107e
Biological: BCG
Biological: i.m. placebo
Arm 4 (phase 1b)
Placebo Comparator group
Description:
Placebo
Treatment:
Biological: i.d. placebo
Biological: Intranasal H107e
Biological: i.m. placebo

Trial contacts and locations

1

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Central trial contact

Pernille Tingskov

Data sourced from clinicaltrials.gov

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