NCT02414828

Brief Summary

This was a double-blind, randomized, placebo-controlled dose-escalation study in adults recently treated for pulmonary TB. The dose of AERAS-402 increased in successive dose groups. Enrollment into a dose group was sequential. Enrollees were stratified based on time from the start of TB treatment. The "on-TB-treatment" stratum started TB treatment between 1 and 4 months (30 to 120 calendar days) prior to Study Day 0. The "post-TB-treatment" stratum started TB treatment at least 12 months (360 calendar days) prior to Study Day 0. Subjects were randomized to receive a placebo or AERAS-402 vaccine. In Dose Groups 1 and 2, subjects were randomized to receive a single injection of AERAS-402 or placebo. Dose Group 3 subjects were randomized to receive two injections on study day 0 and study day 42 of AERAS-402 or placebo.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Oct 2008

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2008

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2010

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2010

Completed
4.4 years until next milestone

First Submitted

Initial submission to the registry

April 8, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 13, 2015

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 4, 2016

Completed
Last Updated

May 4, 2016

Status Verified

April 1, 2016

Enrollment Period

1.7 years

First QC Date

April 8, 2015

Results QC Date

March 4, 2016

Last Update Submit

April 1, 2016

Conditions

Outcome Measures

Primary Outcomes (4)

  • Number of Participants With Solicited and Unsolicited AEs

    All adverse events will be summarized to examine the relationship between dose levels including number (percentage) of solicited and unsolicited adverse events (AEs), and number (percentage) of subjects with newly abnormal post-vaccination laboratory values based on predefined toxicity criteria.

    182 days

  • Forced Expiratory Volume in One Second (FEV1)

    Maximum number of subjects with deterioration \>10% from baseline, at any time point. in forced expiratory volume in one second (FEV1)

    182 days

  • Forced Vital Capacity (FVC)

    Maximum number of subjects with deterioration \>10% from baseline, at any time point, in forced vital capacity (FVC)

    182 days

  • Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Maximum number of subjects with deterioration \>15% from baseline, at any time point, in diffusing capacity of the lung for carbon monoxide (DLCO)

    182 Days

Secondary Outcomes (4)

  • Immunogenicity of AERAS-402 Based on the Percentage of CD4 Cells of Participants in the "on TB Treatment" Stratum

    42 days post dose

  • Immunogenicity of AERAS-402 Based on the Percentage of CD8 Cells of Participants in the "on TB Treatment" Stratum

    42 days post dose

  • Immunogenicity of AERAS-402 Based on the Percentage of CD4 Cells of Participants in the "Post TB Treatment" Stratum

    42 days post dose

  • Immunogenicity of AERAS-402 Based on the Percentage of CD8 Cells of Participants in the "Post TB Treatment" Stratum

    42 days post dose

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo control: 1.0 mL sterile buffer containing 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non animal source) and water.

Biological: Placebo

AERAS-402 3 x 10^8 vp

EXPERIMENTAL

AERAS-402: 1.0 mL containing 3 x 10\^8 vp/mL suspended in 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non animal source) and water.

Biological: AERAS-402 3 x 10^8 vp

AERAS-402 3 x 10^9 vp

EXPERIMENTAL

AERAS-402: 1.0 mL containing 3 x 10\^9 vp/mL suspended in 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non animal source) and water.

Biological: AERAS-402 3 x 10^9 vp

AERAS-402 3 x 10^10 vp

EXPERIMENTAL

AERAS-402: 1.0 mL containing 3 x 10\^10 vp/mL suspended in 20 mM Tris buffer, 2 mM MgCl2, 25 mM NaCl, 10% w/v sucrose, 0.02% w/v PS-80 (polysorbate-80, non animal source) and water.

Biological: AERAS-402 3 x 10^10 vp

Interventions

PlaceboBIOLOGICAL

This is the identical buffer solution in which AERAS-402 is formulated. The placebo (1.0 mL volume) was administered by intramuscular (IM) injection to the deltoid area on Study Day 0 for groups 1 and 2 and Study Day 0 and 42 for group 3.

Also known as: Sterile buffer
Placebo

AERAS-402 was administered by single intramuscular (IM) injection to the deltoid area on Study Day 0

Also known as: AERAS-402
AERAS-402 3 x 10^8 vp

AERAS-402 was administered by single intramuscular (IM) injection to the deltoid area on Study Day 0

Also known as: AERAS-402
AERAS-402 3 x 10^9 vp

AERAS-402 was administered by intramuscular (IM) injection to the deltoid area on Study Days 0 and 42.

Also known as: AERAS-402
AERAS-402 3 x 10^10 vp

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Is male or female.
  • Is age 18 through 45 years on Study Day 0.
  • Has completed the written informed consent process.
  • Has a history of pulmonary tuberculosis diagnosed by either a sputum smear positive for acid-fast bacilli (AFB) or a sputum culture positive for Mtb.
  • Has initiated effective chemotherapy for tuberculosis between one month (30 days) and four months (120 days) before Study Day 0, with improvement in clinical signs and/or symptoms of disease,
  • OR:
  • has initiated effective chemotherapy for tuberculosis at least 12 months (360 days) before Study Day 0, and is considered cured.
  • For subjects currently receiving chemotherapy for tuberculosis they must have been fully compliant with previously prescribed tuberculosis therapy and agree to complete currently prescribed tuberculosis therapy.
  • Agrees to avoid elective surgery for the full duration of the study.
  • For female subjects: agrees to avoid pregnancy for the full duration of the study.
  • Agrees to stay in contact with the study site for the full duration of the study, providing updated contact information as necessary, and has no current plans to move from the study area during the duration of the study.
  • Has completed simultaneous enrollment in Aeras Vaccine Development Registry Protocol.

You may not qualify if:

  • Fever ≥37.5°C.
  • Evidence of a new acute illness that may compromise the safety of the subject in the study.
  • Evidence of any significant active infection other than tuberculosis.
  • Evidence of central nervous system tuberculosis or pleural tuberculosis.
  • Previous medical history that may compromise the safety of the subject in the study, including but not limited to: severe impairment of pulmonary function from tuberculosis infection or other pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected progressive neurological disease; or uncontrolled epilepsy or infantile spasms.
  • Evidence of any systemic disease or any acute or chronic illness that may interfere with the evaluation of the safety of the vaccine.
  • History or laboratory evidence of any past, present or future possible immunodeficiency state, including but not limited to any laboratory indication of HIV-1 infection.
  • History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine.
  • Received any investigational drug therapy or vaccine within 182 days before the first dose of study vaccine in this protocol.
  • Received any adenovirus-based vaccine previously.
  • For female subjects: Currently pregnant, lactating/nursing, or a positive serum or urine βhCG
  • Severe anemia, defined as a hemoglobin less than 10 g/dL or a hematocrit less than 30 percent.
  • Urine toxicology screen positive for opiates, cocaine, or amphetamines.
  • Anal intercourse with another man at least one time (with or without condoms).
  • Exchange of goods, money, services or drugs for sex.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Cape Town Lung Institute Pty (Ltd)

Cape Town, Mowbray, 7700, South Africa

Location

Related Publications (1)

  • van Zyl-Smit RN, Esmail A, Bateman ME, Dawson R, Goldin J, van Rikxoort E, Douoguih M, Pau MG, Sadoff JC, McClain JB, Snowden MA, Benko J, Hokey DA, Rutkowski KT, Graves A, Shepherd B, Ishmukhamedov S, Kagina BMN, Abel B, Hanekom WA, Scriba TJ, Bateman ED. Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial. Am J Respir Crit Care Med. 2017 May 1;195(9):1171-1180. doi: 10.1164/rccm.201603-0654OC.

MeSH Terms

Conditions

Tuberculosis

Interventions

AERAS-402

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Results Point of Contact

Title
Ann Ginsberg, Chief Medical Officer
Organization
Aeras

Study Officials

  • Eric Bateman, MD

    University of Cape Town Lung Institute Pty (Ltd)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2015

First Posted

April 13, 2015

Study Start

October 1, 2008

Primary Completion

July 1, 2010

Study Completion

November 1, 2010

Last Updated

May 4, 2016

Results First Posted

May 4, 2016

Record last verified: 2016-04

Locations