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

• ClinicalTrials.gov Identifier: NCT06050356
• Recruitment Status: Recruiting
• First Posted: September 22, 2023
• Last Update Posted: March 18, 2024
• Sponsor: Statens Serum Institut
• Collaborators: Aurum Institute; Bill and Melinda Gates Foundation; Leiden University Medical Center; South African Tuberculosis Vaccine Initiative
• Information provided by (Responsible Party): Statens Serum Institut

Tracking Information

• First Submitted Date: September 17, 2023
• First Posted Date: September 22, 2023
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: March 14, 2024
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 17, 2023)

• Percentage of participants with solicited injection site reactions recorded up to seven days after each i.m. vaccination (phase 1a) [ Time Frame: Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose) ]
• Percentage of participants with solicited systemic reactions recorded up to seven days after each i.m. vaccination (phase 1a) [ Time Frame: Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose) ]
• Percentage of participants with unsolicited adverse events occurring up to 28 days after last i.m. vaccination (phase 1a) [ Time Frame: Up to Day 57 (28 days after second dose) ]
• Percentage of participants with adverse events of special interest occurring up to last visit (phase 1a) [ Time Frame: Up to Day 197 (196 days after first dose) ]
  Adverse events of special interest represent a subset of AEs that include autoimmune diseases and other systemic disorders of interest which could potentially have an autoimmune etiology
• Percentage of participants with serious adverse events (SAEs) occurring up to last visit (phase 1a) [ Time Frame: Up to Day 197 (196 days after first dose) ]
• Percentage of participants with solicited adverse events occurring up to seven days after i.n. mucosal recall (phase 1a) [ Time Frame: Day 85 up to Day 92 (7 days after mucosal recall) ]
  This outcome is only measured for phase 1a Arm 4a and Arm 4b. Solicited adverse events related to mucosal recall consist of local and systemic reactions
• Percentage of participants with unsolicited adverse events occurring up to 28 days after i.n. mucosal recall (phase 1a) [ Time Frame: Day 85 up to Day 113 (28 days after mucosal recall) ]
  This outcome is only measured for phase 1a Arm 4a and Arm 4b
• Percentage of participants with solicited injection site reactions recorded up to seven days after each vaccination (i.m. or i.d.) (phase 1b) [ Time Frame: Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose) ]
• Percentage of participants with solicited systemic reactions recorded up to seven days after each vaccination (i.m. or i.d.) (phase 1b) [ Time Frame: Up to Day 8 (7 days after first dose) and Day 29 up to Day 36 (7 days after second dose) ]
• Percentage of participants with unsolicited adverse events occurring up to 28 days after last vaccination (phase 1b) [ Time Frame: Up to Day 57 (28 days after second dose) ]
• Percentage of participants with adverse events of special interest occurring up to last visit (phase 1b) [ Time Frame: Up to Day 281 (280 days after first dose) ]
  Adverse events of special interest represent a subset of AEs that include autoimmune diseases and other systemic disorders of interest which could potentially have an autoimmune etiology
• Percentage of participants with SAEs occurring up to last visit (phase 1b) [ Time Frame: Up to Day 281 (280 days after first dose) ]
• Percentage of participants with solicited adverse events occurring up to seven days after i.n. mucosal recall (phase 1b) [ Time Frame: Day 211 up to Day 218 (7 days after mucosal recall) ]
  Solicited adverse events related to mucosal recall consist of local and systemic reactions
• Percentage of participants with unsolicited adverse events occurring up to 28 days after i.n. mucosal recall (phase 1b) [ Time Frame: Day 211 up to Day 239 (28 days after mucosal recall) ]
• Frequencies of H107e-specific T-cells producing IFN-γ and/or IL-17 induced by H107e/CAF®10b vs. placebo and vs. H107e/CAF®10b + BCG before first i.m. vaccination and two weeks after the second i.m. vaccination (phase 1b) [ Time Frame: Day 1 and Day 43 ]
  PBMC ELISpot or whole blood ICS is used to evaluate this outcome

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 17, 2023)

• Frequencies of H107e-specific IFN-γ producing T-cells before first i.m. vaccination and two weeks after the second i.m. vaccination (phase 1a) [ Time Frame: Day 1 and Day 43 ]
  ELISpot assay on PBMCs is used to evaluate this outcome
• Frequencies of BCG-specific T-cells producing IFN-γ and/or IL-17 induced by H107e/CAF®10b + BCG vs. BCG alone (phase 1b) [ Time Frame: Day 1 and Day 85 ]
  PBMC ELISpot or whole blood ICS is used to evaluate this outcome

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-in-Human Trial of the Novel Tuberculosis Vaccine Candidate, H107e/CAF®10b
• Official Title: A Phase 1a, Dose-finding, Open-label Trial Followed by a Phase 1b, Double-blind, Randomised, Placebo-controlled Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of the Tuberculosis Subunit Vaccine H107e/CAF®10b in Adults

Brief Summary

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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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).

Masking: None (Open Label)
Masking Description:

Phase 1a is open label

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

Primary Purpose: Prevention

• Condition: Healthy

Intervention

• Biological: H107e
  Participants will receive two i.m. injections of 20 µg unadjuvanted H107e on Day 1 and Day 29
• Biological: CAF®10b
  Participants will receive two i.m. injections of CAF®10b (full adjuvant dose) on Day 1 and Day 29
• 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
• 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
• Biological: Low dose intranasal H107e
  Participants will receive one i.n. administration of 15 µg H107e (low dose intranasal H107e) on Day 85
• Biological: Full dose intranasal H107e
  Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 85
• 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
• Biological: i.m. placebo
  Participants will receive two i.m. injections of placebo on Day 1 and Day 29
• Biological: BCG
  Participants will receive one i.d. injection of BCG on Day 1
• Biological: i.d. placebo
  Participants will receive one i.d. injection of placebo on Day 1
• Biological: Intranasal H107e
  Participants will receive one i.n. administration of 30 µg H107e (full dose intranasal H107e) on Day 211

Study Arms

• Experimental: Arm 1 (phase 1a)
  H107e
  Intervention: Biological: H107e
• Experimental: Arm 2 (phase 1a)
  CAF®10b
  Intervention: Biological: CAF®10b
• Experimental: Arm 3 (phase 1a)
  H107e/CAF®10b - low adjuvant dose
  Intervention: Biological: H107e/CAF®10b - low adjuvant dose
• Experimental: Arm 4a (phase 1a)
  H107e/CAF®10b - full adjuvant dose - low dose intranasal H107e
  Interventions:

  • Biological: H107e/CAF®10b - full adjuvant dose
  • Biological: Low dose intranasal H107e
• Experimental: Arm 4b (phase 1a)
  H107e/CAF®10b - full adjuvant dose - full dose intranasal H107e
  Interventions:

  • Biological: H107e/CAF®10b - full adjuvant dose
  • Biological: Full dose intranasal H107e
• Experimental: Arm 1 (phase 1b)
  H107e/CAF®10b
  Interventions:

  • Biological: H107e/CAF®10b
  • Biological: i.d. placebo
  • Biological: Intranasal H107e
• Experimental: Arm 2 (phase 1b)
  H107e/CAF®10b + BCG
  Interventions:

  • Biological: H107e/CAF®10b
  • Biological: BCG
  • Biological: Intranasal H107e
• Active Comparator: Arm 3 (phase 1b)
  BCG
  Interventions:

  • Biological: i.m. placebo
  • Biological: BCG
  • Biological: Intranasal H107e
• Placebo Comparator: Arm 4 (phase 1b)
  Placebo
  Interventions:

  • Biological: i.m. placebo
  • Biological: i.d. placebo
  • Biological: Intranasal H107e

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 17, 2023): 140
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2026
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pernille Tingskov; +45 3268 8505; PNT@ssi.dk

• Listed Location Countries: South Africa

Administrative Information

• NCT Number: NCT06050356
• Other Study ID Numbers: nTB-01; INV-042397 ( Other Grant/Funding Number: Bill & Melinda Gates Foundation ); DOH-27-102023-7355 ( Registry Identifier: South African National Clinical Trials Registry )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Statens Serum Institut
• Original Responsible Party: Same as current
• Current Study Sponsor: Statens Serum Institut
• Original Study Sponsor: Same as current

Collaborators

• Aurum Institute
• Bill and Melinda Gates Foundation
• Leiden University Medical Center
• South African Tuberculosis Vaccine Initiative

Investigators

• Study Chair: Gavin Churchyard, PhD; Aurum Institute
• Study Chair: Rasmus Mortensen, PhD; Statens Serum Institut

• PRS Account: Statens Serum Institut
• Verification Date: March 2024