TuberculosisPhase 1C-012-402NCT02430506
A Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QFT (+) and (-) Adults Without Evidence of TB
A Phase 1 study testing AERAS-402 in people with Tuberculosis, run by Aeras at 1 site in Kenya.
Trial summary
The available live tuberculosis vaccine Bacillus Calmette-Guérin (BCG) provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- AERAS-402
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteKenya
- Study dates
- Sep 2008to Jul 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Is male or female
- Is age 18 through 45 years on Study Day 0
- Has completed the written informed consent process
- Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
- Females: Ability to avoid pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
- Has general good health, confirmed by medical history and physical examination.
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- Has Body Mass Index (BMI) between 18 and 30 (wt./ht.2) by nomogram
- Has ability to complete follow-up period of 182 days as required by the protocol
- Is able and willing to commit to avoiding elective surgery for the duration of the study.
- Is able and willing to stay in contact with the study site for the duration of the study.
- Has completed simultaneous enrollment in Aeras Vaccine Development Registry Protocol.
Who cannot join
- Acute illness on the day of randomization.
- Fever ≥37.5°C on the day of randomization.
- Evidence of any significant active infection on the day of randomization.
- Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted).
- Received immunoglobulin or blood products within 45 days before entry into the study.
- Received any investigational drug therapy or vaccine within 182 days before the first dose of study vaccine in this protocol.
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- Received any standard vaccine within 45 days before the first dose of study vaccine in this protocol, through the last study visit (the use of licensed drugs or vaccines medically indicated during the study is permitted).
- Received any adenovector based vaccine previously.
- Current chronic drug therapy including hormones such as thyroxin, insulin, etc. (Estrogen and progesterone replacement and contraceptives are permitted)
- History or laboratory evidence of any past, present or future possible immunodeficiency state which will include, but is 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.
- Previous medical history that may compromise the safety of the subject in the study.
- Evidence of a new acute illness that may compromise the safety of the subject in the study.
- Pregnant or lactating/nursing females.
- Evidence of chronic hepatitis including a positive test for hepatitis B core antibody, or hepatitis C antibody.
- Inability to discontinue daily medications except contraceptives during the study.
- History of alcohol or drug abuse within the past 2 years.
- Tobacco or cannabis smoking three or more days per week
- Positive urine test for illicit drugs (opiates, cocaine, amphetamines).
- History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, including axillary lymphadenopathy
- History or evidence (including chest X-ray) of active or past tuberculosis
- Abnormal hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, absolute lymphocyte count, PT, PTT, GGT, ALT, AST, total bilirubin, ALP, and creatinine drawn within 36 hours of randomization. CPK must be drawn but the CPK value is not an exclusion criteria.
- History of high risk sexual behaviors.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Randomized Placebo-controlled Double-blind Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold (+) and QuantiFERON®-TB Gold (-) Adults Without Evidence of Tuberculosis.
The available live tuberculosis vaccine Bacillus Calmette-Guérin (BCG) provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication deficient adenovirus vaccine that may increase T cell immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals in Kenya who have already been vaccinated with BCG.
Read the detailed description
This Phase I study will be conducted as a double-blind, randomized, placebo-controlled study in 20 healthy adult subjects. The study will enroll 10 subjects who are QFT-G positive at screening and 10 subjects who are QFT-G negative at screening. Within QFT-G group, subjects will be randomized to receive AERAS-402 or placebo in a ratio of 4:1. One dose level of AERAS-402 (3 x 10^10 vp) will be investigated in this study. All subjects will receive a single dose of study vaccine (AERAS-402 or placebo) on Study Day 0 and a second dose of study vaccine (AERAS-402 or placebo) on Study Day 56. All vaccinations will be administered by IM injection into the deltoid muscle.
The sample size was selected as adequate for preliminary safety evaluations and initial immunogenicity reviews for this phase study, rather than for statistical reasons. If no serious adverse events are observed in 16 subjects who receive AERAS-402, the upper bound of the 95% confidence interval on the rate of serious adverse event occurrence is 17.1 percent.
The selection of AERAS-402 dose level for evaluation in this study was derived from animal studies and based on the safety profile for the completed and ongoing clinical studies in the U.S. and South Africa.The total duration of follow-up is 182 days for each subject with a total of eleven follow-up clinic visits. The study is planned at a single site in Kisumu, Kenya.
- Conditions
- Tuberculosis
- Being tested
- Placebo, AERAS-402
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboBiological
This is the identical buffer solution in which AERAS-402 is formulated.
AERAS-402Biological
Given to 8 participants that were QFT-G(-) at screening and 8 participants that were GFT-G(+) at screening.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 1.0 mL sterile buffer administered by intramuscular (IM) injection to deltoid area on days 0 and 56. Receives: Biological: Placebo |
| AERAS-402 | Experimental | 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. Administered intramuscular (IM) injection to deltoid area on days 0 and 56. Receives: Biological: AERAS-402 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold In-Tube test (QFT-G)(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Collection of solicited and unsolicited adverse events.
Measured: Day 0 thru Day 182
Secondary outcomes (1)
Immunogenicity profile of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QFT-G(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Percentage of CD4 and CD8 T cells that produce any of three cytokines (IFN-γ, TNF-α, and/or IL-2) or a combination of the three cytokines simultaneously.
Measured: Day 0 thru day 182
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2015 (estimated)
- Study startSep 2008
- Primary completionJun 2009
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Doug Walsh, MD, Principal investigator, U. S. Army Medical Research Unit- Kenya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02430506
- Sponsor's protocol ID
- C-012-402
- Acronym
- C-012-402
- Status last verified
- Apr 2016
- First submitted
- 27 Apr 2015
- Last updated
- 27 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Walsh DS, Owira V, Polhemus M, Otieno L, Andagalu B, Ogutu B, Waitumbi J, Hawkridge A, Shepherd B, Pau MG, Sadoff J, Douoguih M, McClain JB; Aeras C-012-402 Study Team. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON((R))-TB Gold (+) Kenyan adults without evidence of tuberculosis. Vaccine. 2016 May 5;34(21):2430-2436. doi: 10.1016/j.vaccine.2016.03.069. Epub 2016 Mar 26.
PubMed 27026148
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized Placebo-controlled Double-blind Study to Evaluate Safety and Immunogenicity of AERAS-402 Administered in HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold (+) and QuantiFERON®-TB Gold (-) Adults Without Evidence of Tuberculosis.
- ClinicalTrials.gov ID
- NCT02430506
- Acronym / sponsor ID
- C-012-402 / C-012-402
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 30 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The available live tuberculosis vaccine Bacillus Calmette-Guérin (BCG) provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication deficient adenovirus vaccine that may increase T cell immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals in Kenya who have already been vaccinated with BCG.
Detailed description
This Phase I study will be conducted as a double-blind, randomized, placebo-controlled study in 20 healthy adult subjects. The study will enroll 10 subjects who are QFT-G positive at screening and 10 subjects who are QFT-G negative at screening. Within QFT-G group, subjects will be randomized to receive AERAS-402 or placebo in a ratio of 4:1. One dose level of AERAS-402 (3 x 10^10 vp) will be investigated in this study. All subjects will receive a single dose of study vaccine (AERAS-402 or placebo) on Study Day 0 and a second dose of study vaccine (AERAS-402 or placebo) on Study Day 56. All vaccinations will be administered by IM injection into the deltoid muscle.
The sample size was selected as adequate for preliminary safety evaluations and initial immunogenicity reviews for this phase study, rather than for statistical reasons. If no serious adverse events are observed in 16 subjects who receive AERAS-402, the upper bound of the 95% confidence interval on the rate of serious adverse event occurrence is 17.1 percent.
The selection of AERAS-402 dose level for evaluation in this study was derived from animal studies and based on the safety profile for the completed and ongoing clinical studies in the U.S. and South Africa.The total duration of follow-up is 182 days for each subject with a total of eleven follow-up clinic visits. The study is planned at a single site in Kisumu, Kenya.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Biological: Placebo1.0 mL sterile buffer administered by intramuscular (IM) injection to deltoid area on days 0 and 56. |
| AERAS-402 | Experimental | Biological: AERAS-4021.0 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. Administered intramuscular (IM) injection to deltoid area on days 0 and 56. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Is male or female
- Is age 18 through 45 years on Study Day 0
- Has completed the written informed consent process
- Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
- Females: Ability to avoid pregnancy from 28 days prior to administration of the study vaccine through the end of the study.
Key exclusion criteria (23 listed)
- Acute illness on the day of randomization.
- Fever ≥37.5°C on the day of randomization.
- Evidence of any significant active infection on the day of randomization.
- Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted).
- Received immunoglobulin or blood products within 45 days before entry into the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboThis is the identical buffer solution in which AERAS-402 is formulated. | Biological | Placebo |
| AERAS-402Given to 8 participants that were QFT-G(-) at screening and 8 participants that were GFT-G(+) at screening. | Biological | AERAS-402 |
Primary outcome
Safety of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold In-Tube test (QFT-G)(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Time frame: Day 0 thru Day 182
Collection of solicited and unsolicited adverse events.
1 secondary outcome
Immunogenicity profile of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QFT-G(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya.
Time frame: Day 0 thru day 182
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2016.
- Background: PubMed 27026148Walsh DS, Owira V, Polhemus M, Otieno L, Andagalu B, Ogutu B, Waitumbi J, Hawkridge A, Shepherd B, Pau MG, Sadoff J, Douoguih M, McClain JB; Aeras C-012-402 Study Team. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON((R))-TB Gold (+) Kenyan adults without evidence of tuberculosis. Vaccine. 2016 May 5;34(21):2430-2436. doi: 10.1016/j.vaccine.2016.03.069. Epub 2016 Mar 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Doug Walsh, MD principal investigator
U. S. Army Medical Research Unit- Kenya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AERAS-402 in people with Tuberculosis, run by Aeras at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of AERAS-402 in healthy, HIV-negative, BCG-vaccinated, QuantiFERON®-TB Gold In-Tube test (QFT-G)(+) and QFT-G(-) adults without evidence of tuberculosis disease in Kenya. (time frame: Day 0 thru Day 182). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02430506, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2016.