MVA85A Aerosol vs Intramuscular Vaccination in Adults With Latent Mycobacterium Tuberculosis (M. tb) Infection

• Sponsor: University of Oxford (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02532036
• Collaborator: University of Birmingham (Other)
• Enrollment: 2
• Locations: 5
• Arms: 3
• Duration (Months): 37.1
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

TB040 is a clinical trial to investigate and compare the effects of a candidate Tuberculosis (TB) vaccine, MVA85A, administered by the aerosol inhaled route and the intramuscular route in healthy adult volunteers who are latently infected with Mycobacterium tuberculosis.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Biological: Aerosol inhaled MVA85A; Biological: Intramuscular MVA85A; Biological: Intramuscular Saline placebo; Biological: Aerosol inhaled Saline placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Phase I Trial to Compare the Safety and Immunogenicity of Candidate TB Vaccine MVA85A Administered by the Aerosol Inhaled Route and the Intramuscular Route in Healthy Adult Volunteers Who Are Latently Infected With Mycobacterium Tuberculosis
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Oct 4, 2018
• Actual Study Completion Date: Oct 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Starter Group Receive 1x10^7 pfu aerosol inhaled MVA85A at day 0.	Biological: Aerosol inhaled MVA85A; Other Names: MVA85A
Experimental: Group A Receive 5x10^7 pfu aerosol inhaled MVA85A, and intramuscular saline placebo both at day 0.	Biological: Aerosol inhaled MVA85A; Other Names: MVA85A ; Biological: Intramuscular Saline placebo; Other Names: Saline
Experimental: Group B Receive 5x10^7 pfu intramuscular MVA85A, and aerosol inhaled saline placebo both at day 0.	Biological: Intramuscular MVA85A; Other Names: MVA85A ; Biological: Aerosol inhaled Saline placebo; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Adverse Events (AE) [Up to Day 168]

   Actively and passively collected data on adverse events via diary card for 14 days after vaccination and at each visit over 6 months.

Secondary Outcome Measures

1. Laboratory Markers of Immunity [Up to Day 168]

   Evaluation of ex-vivo ELISpot and intracellular cytokine staining in blood and bronchoalveolar lavage (BAL) samples.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Volunteers must meet all of the following criteria to enter the trial:

• Healthy adult aged 18-55 years

• Resident in or near Oxford, Birmingham or London for the duration of the trial period

• Screening IGRA positive

• Ineligible for chemoprophylaxis for latent M.tb infection, declined prophylaxis or considered low risk due to distant contact history

• Chest Computed Tomography (CT) normal; or abnormal with features consistent with primary M.tb infection but no features suggestive of active disease

• No relevant findings in medical history or on physical examination

• Allow the Investigators to discuss the individual's medical history with their General Practitioner

• Use effective contraception for the duration of the trial period (females only)

• Refrain from blood donation during the trial

• Give written informed consent

• Allow the Investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical trials

• Able and willing (in the Investigator's opinion) to comply with all the trial requirements

Exclusion Criteria:

Volunteers must meet none of the following criteria to enter the trial:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the trial period

• Prior vaccination with candidate vaccine MVA85A, candidate vaccine FP85A,any other recombinant MVA vaccine or any other candidate TB vaccine

• Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date

• Clinically significant history of skin disorder, allergy, atopy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, neurological illness, psychiatric disorder, drug or alcohol abuse

• 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 trial vaccine, sedative drugs, or any local or general anaesthetic agents

• Pregnancy, lactation or intention to become pregnant during trial period

• Any respiratory disease, including asthma

• Current smoker

• Clinically significant abnormality on screening CT thorax

• Clinically significant abnormality of pulmonary function tests

• Any nasal, pharyngeal, or laryngeal finding which precludes bronchoscopy

• Current use of any medication taken through the nasal or inhaled route including cocaine or other recreational drugs

• Clinical, radiological, or laboratory evidence of current active TB disease

• Past treatment for TB disease

• Any clinically significant abnormality of screening blood or urine tests

• Positive HBsAg, HCV or HIV antibodies

• Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the trial or impair interpretation of the trial data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LE
2	John Warin Ward, Churchill Hospital	Oxford	Oxfordshire	United Kingdom	OX3 7LE
3	NIHR Wellcome Trust Clinical Research Facility, University of Birmingham	Birmingham	West Midlands	United Kingdom	B15 2TH
4	NIHR/Wellcome Trust King's Clinical Research Facility	London		United Kingdom
5	Royal Free Hospital NHS Foundation Trust	London		United Kingdom

Sponsors and Collaborators

• University of Oxford
• University of Birmingham

Investigators

• Study Director: Helen McShane, University of Oxford
• Principal Investigator: Paul Moss, University of Birmingham
• Principal Investigator: Marc Lipman, Royal Free Hostpital
• Principal Investigator: Felicity Perrin, King's College Hospital NHS Trust

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 19, 2017

More Information

Publications

None provided.

• Responsible Party: University of Oxford
• ClinicalTrials.gov Identifier: NCT02532036
• Other Study ID Numbers: TB040
• First Posted: Aug 25, 2015
• Last Update Posted: Aug 31, 2020
• Last Verified: Nov 1, 2018

• Keywords provided by University of Oxford: MVA85A; Tuberculosis; Vaccine; Aerosol
• Additional relevant MeSH terms: Tuberculosis

Study Results

Participant Flow

Arm/Group Title	Starter Group	Group A
Arm/Group Description	Receive 1x10^7 pfu aerosol inhaled MVA85A at day 0.	Receive 5x10^7 pfu aerosol inhaled MVA85A
Period Title: Overall Study
STARTED	2	0
COMPLETED	2	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Starter Group
Arm/Group Description	Received 1x10^7 pfu aerosol inhaled MVA85A at day 0.
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United Kingdom	2 100%

Outcome Measures

1. Primary Outcome

Title	Adverse Events (AE)
Description	Actively and passively collected data on adverse events via diary card for 14 days after vaccination and at each visit over 6 months.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Starter Group
Arm/Group Description	Receive 1x10^7 pfu aerosol inhaled MVA85.
Measure Participants	2
Count of Participants [Participants]	2 100%

2. Secondary Outcome

Title	Laboratory Markers of Immunity
Description	Evaluation of ex-vivo ELISpot and intracellular cytokine staining in blood and bronchoalveolar lavage (BAL) samples.
Time Frame	Up to Day 168

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	All AEs occurring for 6 months following the vaccination that were observed by the investigator or reported by the volunteer, whether or not attributed to study medication, were recorded by volunteers on electronic diary cards or by staff on CRFs.
Arm/Group Title	Starter Group
Arm/Group Description	Received 1x10^7 pfu aerosol inhaled MVA85A at day 0.
All Cause Mortality
	Starter Group
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Starter Group
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Starter Group
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Investigations
radiological changes	1/2 (50%)	1

Limitations/Caveats

Due to significant challenges with recruitment at all UK sites this study has been terminated early.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.