A Controlled Human Infection Model (CHIM) With Intradermal BCG in Malawi

NCT06178666 | Not Yet Recruiting DMC

• 2 other identifiers: 23-Marvels-00323-083
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Despite tremendous efforts, an effective tuberculosis (TB) vaccine remains elusive. TB continues to infect and kill many. In 2021, TB infected more than 10 million and killed 1.6 million people. To date, the M.bovis bacille Calmette Guerin (BCG) is the only licensed vaccine against tuberculosis (TB). Efforts to come up with new and effective vaccines have not been successful. Partially, the lack of suitable disease models and protection correlates hinders the research of new vaccines. Controlled human infection model studies (CHIM) involve administering disease-causing microbes to healthy individuals, with continued monitoring of disease response. These studies have been used to study malaria, typhoid, pneumococcal pneumonia and the recent SARS-CoV-2 vaccines. The BCG-Controlled Human Infection Model (BCG-CHIM) will allow accurate dosing with safe mycobacteria as well as minimal tissue sampling to understand immunity to mycobacteria. Considering that the M. bovis BCG is a safe living Mycobacteria, it can be used as a CHIM against which to test new vaccines.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Culture and PCR ascertainment of BCG load

  BCG will be quantified in 4mm skin punch biopsy

  14 days

Secondary Outcomes (1)

• Immunological response to BCG

  14 days

Other Outcomes (2)

• Microbiology and immunology

  Day 2, 7, 14, 21, 28

• Lung cellular and humoral immune response

  Day 14 after inoculation

Study Arms (3)

Low dose of BCG being tested in dose ranging study

EXPERIMENTAL

The lowest dose of BCG (standard Malawi BCG vaccine (BCG Bulgaria 150000-600000 cfu) given as intradermal injection) will be used to determine safety and feasibility. The investigators do not expect to be able to meet study endpoints in this arm which will recruit 10 subjects.

Biological: BCG

Mid-range dose BCG being tested in dose ranging study

EXPERIMENTAL

The mid-range dose of BCG (4x standard Malawi dose (BCG Bulgaria 600000-2400000 cfu intradermal) and equal to the model tested in Oxford, UK) will be used to determine safety and feasibility. The investigators hope to to be able to meet study endpoints (measuring microbiological and immunological features of BCG skin lesion) in this arm which will recruit 10 subjects.

Biological: BCG

High dose BCG being tested in dose ranging study

EXPERIMENTAL

The highest dose of BCG (10x standard Malawi dose (BCG Bulgaria 2400000-9600000 cfu intradermal) and equal to USA dose used in Seattle) will be used to determine safety and feasibility. The investigators expect to be able to meet study endpoints in this arm which will recruit 10 subjects. In the event that study endpoints are met in the mid-range dose, the investigators will introduce a rifampicin dosing schedule to this arm.

Biological: BCG

Interventions

BCG BIOLOGICAL

Three dose levels of intradermal BCG

Also known as: Bacille Calmette Guerin

High dose BCG being tested in dose ranging study; Low dose of BCG being tested in dose ranging study; Mid-range dose BCG being tested in dose ranging study

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18-50 (inclusive)
• Resident near QECH, Blantyre (\<1 hour drive) for the duration of the study period
• Allows the investigators to review the volunteer's medical history in the health passport book.
• Females of childbearing potential with a negative urine pregnancy test at screening and willing to practice adequate birth control measures during the study.
• Fluent spoken English or Chichewa - to ensure a comprehensive understanding of the research project and their proposed involvement.
• Capacity to provide informed consent before joining the study.
• Able and willing (in the investigators opinion) to comply with all the study requirements.

You may not qualify if:

• Laboratory evidence at screening of subclinical M. tb infection as indicated by a positive ELISPOT response to ESAT-6 or CFP-10 antigens. Volunteers discovered to have evidence of latent M. tb infection as defined by a positive ELISPOT test will be referred to the chest clinic for investigation for tuberculosis according to Malawi standard protocols.
• Clinical, radiological, or laboratory evidence of current active TB disease
• Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer, cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, or psychiatric disorder.
• Current medical issues. Volunteers who are excluded from the study because they have been discovered to have a previously undiagnosed condition thought to require further medical attention will be referred appropriately to QECH specialist services for further investigation and treatment.
• Acute respiratory tract infection in the four weeks preceding recruitment
• Any uncontrolled medical or surgical condition at the discretion of the study doctor
• Female participants who are pregnant, or intending to become pregnant, lactating or who Female participants who are unable to take contraception measures during the study.
• Smoking: Current (defined as ≥5/week) or ex-smoker (cigarettes / cigars / smoking of recreational drugs) in the last 6 months. Previous significant smoking history (more than 20 cigarettes per day for 20 years or the equivalent \[\>20 pack years\]).Current alcohol and recreational drug use
• Regularly drinks ≥3units/day (male) or ≥2units/day (female)
• Uses recreational drugs.
• Participants may be excluded at the discretion of the research clinician.
• Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents
• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the challenge agent.
• Has received any vaccination within one month of screening visit.
• Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the study.

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• Liverpool School of Tropical Medicine, United Kingdom: collaborator
• Fred Hutchinson Cancer Center: collaborator
• University of Liverpool: collaborator
• Malawi-Liverpool-Wellcome Trust Clinical Research Programme: collaborator
• University of Oxford: collaborator

Study Sites (1)

Queen Elizabeth Central Hospital

Blantyre, BT3, Malawi

Location

Related Publications (2)

• Lin LL, Prow TW, Raphael AP, Harrold Iii RL, Primiero CA, Ansaldo AB, Soyer HP. Microbiopsy engineered for minimally invasive and suture-free sub-millimetre skin sampling. F1000Res. 2013 May 2;2:120. doi: 10.12688/f1000research.2-120.v2. eCollection 2013.

  PMID: 24627782 BACKGROUND

• Lei BUW, Yamada M, Hoang VLT, Belt PJ, Moore MH, Lin LL, Flewell-Smith R, Dang N, Tomihara S, Prow TW. Absorbent Microbiopsy Sampling and RNA Extraction for Minimally Invasive, Simultaneous Blood and Skin Analysis. J Vis Exp. 2019 Feb 21;(144). doi: 10.3791/58614.

  PMID: 30855573 BACKGROUND

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Stephen Gordon, MD

  Malawi Liverpool Wellcome Programme

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen B Gordon, MD

CONTACT

265992552382; sgordon@mlw.mw

Neema Toto, BSc Nursing

CONTACT

+265992892117; ntoto@mlw.mw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A feasibility study of a controlled human infection model (CHIM) with intradermal bacillus Calmette-Guérin (BCG) injection in Malawi

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 21, 2023
• Study Start: March 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2026
• Last Updated: December 21, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)