TuberculosisPhase 1NCT02074956
A Phase I Study to Evaluate Safety and Immunogenicity of AERAS 404 Administered in Adults
A Phase 1 study testing AERAS-404 in people with Tuberculosis, run by Aeras at 1 site in Finland.
Trial summary
This Phase I study will be conducted as a randomized, double-blind, dose-escalation study in five groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. 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-404
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteFinland
- Study dates
- May 2008to Oct 2009
- 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
- Has completed written informed consent
- Is male or female
- Is age 18 through 45 years on Study Day 0
- Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
- Has general good health, confirmed by medical history and physical examination
- Has a Body Mass Index (BMI) between 19 and 33
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- Agrees to complete a follow-up period of 182 days as required by the protocol
- Females: Agrees to avoid pregnancy from 28 days prior to Study Day 0 through the follow-up period of 182 days. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses) must agree to avoid pregnancy using an acceptable method
- Agrees to avoid elective surgery for the duration of the study
- Agrees to stay in contact with the investigative site for the study duration
- Completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
Who cannot join
- Acute illness on Study Day 0
- Axillary temperature >=37.5 degrees Celsius on Study Day 0
- Evidence of significant active infection
- Used immunosuppressive medication within 42 days before Study Day 0
- Received immunoglobulin or blood products within 42 days before Study Day 0
- Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0
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- Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study, or any other standard vaccine within 42 days before Study Day 0
- Current chronic drug therapy including hormone replacement such as thyroxin, insulin
- History or laboratory evidence of past, present or future possible immunodeficiency state which include any laboratory indication of HIV infection
- History of allergic disease or reactions, including eczema
- Previous medical history that may compromise safety of the subject in the study
- Evidence of new acute illness that may compromise the safety of subject in the study
- Evidence of chronic hepatitis
- Inability to discontinue daily medications except contraceptives during study period
- History of alcohol or drug abuse within past 2 years
- Tobacco or cannabis smoking three or more days per week
- Positive urine test for illicit drugs
- History or evidence of any systemic disease on physical examination
- History or evidence of active tuberculosis
- Shared a residence within the last year with a individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis
- All females: Positive urine pregnancy test during screening
- Abnormal (per local laboratory parameters) chemistry and hematology parameters
- QuantiFERON®-TB Gold evidence of Mtb infection
- Received a tuberculin skin test within 3 months (90 days) prior to Study Day 0
Trial locations and contacts
1 site in 1 country.
Finland1 site
University of Tampere Vaccine Research Clinic
Biokatu, Pirkanmaa, 33100
About this study
Official title: A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS 404 When Administered as Different IC31 Adjuvant Amounts With Different AERAS-404 (HyVac4) Antigen Amounts in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
This Phase I study will be conducted as a randomized, double-blind, dose-escalation study in five groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. Since BCG-vaccinated individuals are the target population for which AERAS 404 might be indicated, AERAS 404 will be administered to individuals already vaccinated with BCG
Read the detailed description
Sixty subjects will be sequentially enrolled into one of five study groups (i.e., Group 1, Group 2, Group 3, Group 4, or Group 5) with 10 subjects per group in Groups 1-4 and 20 subjects in Group 5. Within each study group, subjects will be randomized to a treatment assignment of either AERAS-404 or placebo control at a ratio of 4:1 (Groups 1-4) or two different dose amounts of AERAS-404 or placebo control at a ratio of 9:9:2 (Group 5) administered by intramuscular injection on Study Day 0 and Study Day 56. The principal investigator will determine an appropriate interval between the vaccinations such that the entire group is not dosed at the same time. All subjects will receive the same treatment on Study Day 0 as they receive on Study Day 56. All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects
- Conditions
- Tuberculosis
- Being tested
- AERAS-404, Placebo
- Keywords
- BCG Vaccinated, HIV Negative
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AERAS-404Biological
Also called H4
AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide.
PlaceboBiological
Also called Sterile Buffer
Sterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 AERAS-404 | Experimental | H4 Antigen at 5 ug IC31 Adjuvant 500 nmol
2 doses at Study days 0 and 56 Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 2 AERAS-404 | Experimental | H4 Antigen at 15 ug IC31 Adjuvant 500 nmol
2 doses at Study days 0 and 56 Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 3 AERAS-404 | Experimental | H4 Antigen at 50 ug IC31 Adjuvant 500 nmol
2 doses at Study days 0 and 56 Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 4 AERAS-404 | Experimental | H4 Antigen at 150 ug IC31 Adjuvant 500 nmol
2 doses at Study days 0 and 56 Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 5 AERAS-404 | Experimental | H4 Antigen at 5 ug or 15 ug IC31 Adjuvant 100 nmol Placebo - sterile buffer
2 doses at Study days 0 and 56 Receives: Biological: AERAS-404; Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events are captured 28 days post each vaccination. The safety profile of AERAS-404 will be summarized by treatment regimen. The number (percentage) of subjects with adverse events will be summarized by MedDRA system organ class (SOC), and preferred term (PT). Additional summaries will present the number (percentage) of subjects with adverse events by severity and by relationship to study vaccine.
Measured: Total duration of study follow up for all subjects is 182 days.
Secondary outcomes (1)
Immunogenicity of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Intracellular cytokine staining will be used to assess immunogenicity. Immune response based on percentages of CD4+ and CD8+ T cells that produced one, two, or three cytokines (IFN-γ, TNF-α, and/or IL-2) in response to stimulation with one of 2 antigenic peptide pools (Ag85B and TB10.4) derived from and representing the entire amino acid sequences of the mycobacterial antigens Ag85B and TB10.4, respectively.
Measured: Immunogenicity was evaluated from blood collected at Study Days 0, 7, 14, 28, 56, 63, 70, 84, and 182. For all subjects, a QuantiFERON-TB Gold test was performed during screening and at Study Day 182
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2014 (estimated)
- Study startMay 2008
- Primary completionOct 2009
- Study completionOct 2009
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
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut
- Responsible party
- Sponsor
- Investigators
- Zhongkai Shi, MD, Study director, AerasTimo Vesikari, MD, Principal investigator, University of Tampere Vaccine Research Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02074956
- Sponsor's protocol ID
- C 006 404
- Other IDs
- C-006-404
- Status last verified
- Mar 2014
- First submitted
- 27 Feb 2014
- Last updated
- 17 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S, Bennett S, McClain JB, Shepherd BM, Li D, Hokey DA, Kromann I, Hoff ST, Andersen P, de Visser AW, Joosten SA, Ottenhoff THM, Andersson J, Brighenti S. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials. Vaccine. 2017 Mar 14;35(12):1652-1661. doi: 10.1016/j.vaccine.2017.01.055. Epub 2017 Feb 17.
PubMed 28216183
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2014. 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 404 When Administered as Different IC31 Adjuvant Amounts With Different AERAS-404 (HyVac4) Antigen Amounts in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
- ClinicalTrials.gov ID
- NCT02074956
- Acronym / sponsor ID
- C 006 404
- Conditions
- Tuberculosis
- Keywords
- BCG Vaccinated, HIV Negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Statens Serum Institut
- Study start
- May 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 28 Feb 2014 (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.
This Phase I study will be conducted as a randomized, double-blind, dose-escalation study in five groups of healthy adult male and female subjects who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection. Since BCG-vaccinated individuals are the target population for which AERAS 404 might be indicated, AERAS 404 will be administered to individuals already vaccinated with BCG
Detailed description
Sixty subjects will be sequentially enrolled into one of five study groups (i.e., Group 1, Group 2, Group 3, Group 4, or Group 5) with 10 subjects per group in Groups 1-4 and 20 subjects in Group 5. Within each study group, subjects will be randomized to a treatment assignment of either AERAS-404 or placebo control at a ratio of 4:1 (Groups 1-4) or two different dose amounts of AERAS-404 or placebo control at a ratio of 9:9:2 (Group 5) administered by intramuscular injection on Study Day 0 and Study Day 56. The principal investigator will determine an appropriate interval between the vaccinations such that the entire group is not dosed at the same time. All subjects will receive the same treatment on Study Day 0 as they receive on Study Day 56. All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 AERAS-404 | Experimental | Biological: AERAS-404, Biological: PlaceboH4 Antigen at 5 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
| Cohort 2 AERAS-404 | Experimental | Biological: AERAS-404, Biological: PlaceboH4 Antigen at 15 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
| Cohort 3 AERAS-404 | Experimental | Biological: AERAS-404, Biological: PlaceboH4 Antigen at 50 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
| Cohort 4 AERAS-404 | Experimental | Biological: AERAS-404, Biological: PlaceboH4 Antigen at 150 ug IC31 Adjuvant 500 nmol 2 doses at Study days 0 and 56 |
| Cohort 5 AERAS-404 | Experimental | Biological: AERAS-404, Biological: PlaceboH4 Antigen at 5 ug or 15 ug IC31 Adjuvant 100 nmol Placebo - sterile buffer 2 doses at Study 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)
- Has completed written informed consent
- Is male or female
- Is age 18 through 45 years on Study Day 0
- Had BCG vaccination at least 5 years ago, documented through medical history or presence of scar
- Has general good health, confirmed by medical history and physical examination
Key exclusion criteria (24 listed)
- Acute illness on Study Day 0
- Axillary temperature >=37.5 degrees Celsius on Study Day 0
- Evidence of significant active infection
- Used immunosuppressive medication within 42 days before Study Day 0
- Received immunoglobulin or blood products within 42 days before Study Day 0
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 |
|---|---|---|
| AERAS-404Also: H4AERAS-404 is comprised of the H4 antigen, a fusion protein of Mycobacterium tuberculosis antigens 85B and TB10.4; and IC31 adjuvant, a combination of a leucine-rich peptide and a synthetic oligonucleotide. | Biological | Cohort 1 AERAS-404, Cohort 2 AERAS-404, Cohort 3 AERAS-404, Cohort 4 AERAS-404, Cohort 5 AERAS-404 |
| PlaceboAlso: Sterile BufferSterile buffer containing 10 mmol Tris and 169 mmol of NaCl in 0.8 mL of aqueous solution. This is the identical buffer solution in which H4 and IC31 are formulated. | Biological | Cohort 1 AERAS-404, Cohort 2 AERAS-404, Cohort 3 AERAS-404, Cohort 4 AERAS-404, Cohort 5 AERAS-404 |
Primary outcome
Safety profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Time frame: Total duration of study follow up for all subjects is 182 days.
Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited adverse events are captured 28 days post each vaccination. The safety profile of AERAS-404 will be summarized by treatment regimen. The number (percentage) of subjects with adverse events will be summarized by MedDRA system organ class (SOC), and preferred term (PT). Additional summaries will present the number (percentage) of subjects with adverse events by severity and by relationship to study vaccine.
1 secondary outcome
Immunogenicity of two injections of AERAS 404 at different dose levels of antigen and adjuvant.
Time frame: Immunogenicity was evaluated from blood collected at Study Days 0, 7, 14, 28, 56, 63, 70, 84, and 182. For all subjects, a QuantiFERON-TB Gold test was performed during screening and at Study 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 17 Mar 2014.
- Derived from this study: PubMed 28216183Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S, Bennett S, McClain JB, Shepherd BM, Li D, Hokey DA, Kromann I, Hoff ST, Andersen P, de Visser AW, Joosten SA, Ottenhoff THM, Andersson J, Brighenti S. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials. Vaccine. 2017 Mar 14;35(12):1652-1661. doi: 10.1016/j.vaccine.2017.01.055. Epub 2017 Feb 17.
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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.
Zhongkai Shi, MD study director
Aeras
Timo Vesikari, MD principal investigator
University of Tampere Vaccine Research Clinic
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-404 in people with Tuberculosis, run by Aeras at 1 site in Finland.
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 24 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 17 Mar 2014. 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 Finland. 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. 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 profile of two injections of AERAS 404 at different dose levels of antigen and adjuvant. (time frame: Total duration of study follow up for all subjects is 182 days.). 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 NCT02074956, 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 17 Mar 2014.