TuberculosisPhase 1C-013-404NCT02420444
A Study for Safety and Immunogenicity of BCG and AERAS-404 in HIV-Negative, TB-Negative, BCG-Naive Adults
A Phase 1 study testing BCG SSI and AERAS-404 in people with Tuberculosis, run by Aeras at 1 site in Switzerland.
Trial summary
70 subjects received BCG intradermally at Study Day -42, then at Study Day 0 were randomized to receive AERAS-404 50 mcg H4/500 nmol IC31 intramuscularly as a 3-dose (N=30) or 2-dose (N=30) regimen, or placebo (N=10). Subjects were vaccinated on Study Days 0, 56, and 231, and followed through Study Day 259. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- BCG SSI and AERAS-404
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2011to Nov 2013
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Had completed the written informed consent process.
- Was male or female.
- Was age ≥ 18 years and ≤ 50 years.
- Agreed to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and had no current plans to move from the study area for the duration of the study.
- Agreed to avoid elective surgery for the duration of the study.
- Had completed simultaneous enrollment in Aeras Vaccine Development Registry protocol.
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- For female subjects: agreed to avoid pregnancy from 28 days prior to Study Day 0 through the duration of the study.
- Had general good health, confirmed by medical history and physical examination.
- Had body mass index (BMI) between 18 and 33 (weight/height2) by nomogram.
Who cannot join
- Oral temperature ≥37.5°C.
- Abnormal CBC laboratory values (per local laboratory parameters) from blood collected at screening (>5% above ULN or >5% below LLN).
- Abnormally elevated laboratory values (per local laboratory parameters) from blood collected at screening for ALT, AST, GGT, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, prothrombin time (PT), or partial thromboplastin time (PTT) (>10% above ULN).
- Abnormal urinalysis that, in the opinion of the investigator, was clinically significant.
- Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines).
- History or evidence of active or latent tuberculosis infection, including a positive QuantiFERON-TB test, a history of a positive TST, or abnormal chest X-ray findings that in the opinion of the investigator were evidence of tuberculosis.
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- Residence longer than 6 months in a high-burden country (per WHO 2010 TB Report).
- Shared a residence within 1 year prior to Study Day -42 with an individual on anti-tuberculosis treatment or with culture- or smear-positive pulmonary tuberculosis.
- Previous treatment for active or latent tuberculosis infection.
- History or evidence of autoimmune disease.
- History or evidence of any past, present, or future possible immunodeficiency state, including laboratory evidence of HIV 1 infection.
- History or evidence of chronic hepatitis, including hepatitis B core antibody or hepatitis C antibody.
- Received a TST within 90 days prior to Study Day -42.
- Received a systemic antibiotic with 14 days prior to Study Day -42.
- Received BCG vaccination or BCG immunotherapy prior to Study Day -42.
- Received investigational Mtb vaccine.
- Participation in any other investigational study during the study period.
- Current household contact with an individual with known significant immunosuppression.
- Occupational exposure that would have put an immunocompromised individual at risk, unless measures could be taken to reduce this risk to an acceptable level (e.g., plaster on the injection site).
- Received immunoglobulin or blood products within 90 days prior to Study Day -42.
- Received any investigational drug therapy or investigational vaccine within 180 days prior to Study Day -42.
- Received any licensed vaccine within 45 days prior to Study Day -42 (note: the use of licensed vaccines medically indicated during the study was permitted at any time).
- Received immunosuppressive medications other than inhaled or topical immunosuppressants within 45 days prior to Study Day -42.
- Inability to discontinue daily medications other than the following during the study: oral contraceptives, vitamins, nonprescription nutritional supplements, aspirin, antihistamines, antihypertensives, antidepressants.
- All female subjects: currently pregnant or lactating/nursing; positive screening urine pregnancy test; or positive urine pregnancy test on the day of any study vaccination.
- History or evidence of allergic disease or reaction that, in the opinion of the investigator, may have compromised the safety of the subject.
- History or evidence of dermatologic disease that, in the opinion of the investigator, may have interfered with the assessment of injection site reactions.
- History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may have interfered with the evaluation of the safety or immunogenicity of the vaccine or compromise the safety of the subject.
- Medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, would make it unlikely that the subject would comply with the protocol.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Centre Hosptialier Universitaire Vaudois (CHUV)
Lausanne, Canton of Vaud
About this study
Official title: A Phase I Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of BCG and AERAS-404 Administered as a Prime-Boost Regimen to HIV-Negative, TB-Negative, BCG-Naive Adults
70 subjects received BCG intradermally at Study Day -42, then at Study Day 0 were randomized to receive AERAS-404 50 mcg H4/500 nmol IC31 intramuscularly as a 3-dose (N=30) or 2-dose (N=30) regimen, or placebo (N=10). Subjects were vaccinated on Study Days 0, 56, and 231, and followed through Study Day 259.
Read the detailed description
A total of 70 subjects who had received BCG at Study Day -42 were randomized on Study Day 0 to receive 3 doses of placebo (N=10); 1 dose of placebo followed by 2 doses of AERAS-404 (N=30; AERAS-404 2 dose regimen); or 3 doses of AERAS-404 (N=30; AERAS-404 3 dose regimen). A total of 69 (98.6%) subjects completed the study; the remaining subject, in the AERAS-404 2 dose regimen, withdrew consent. All 70 subjects received the first and second vaccinations with placebo or AERAS-404 on Study Days 0 and 56, and 67 (95.7%) subjects received the third vaccination on Study Day 231. Three subjects did not receive the Study Day 231 vaccination (2 in the AERAS-404 2 dose regimen, 1 due to withdrawal of consent and 1 due to pregnancy [the subject delivered a healthy boy without complications and was followed to study completion]; and 1 in the AERAS-404 3 dose regimen, due to inability to discontinue daily isotretinoin started after the second vaccination [the subject was followed to study completion]).
- Conditions
- Tuberculosis
- Being tested
- BCG SSI, Placebo, AERAS-404
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG SSIBiological
Also called BCG Vaccine SSI Danish, bacillus Calmette-Guérin
The dose volume administered for BCG was 0.1 mL, and the mode of administration was ID injection to the deltoid area.
PlaceboBiological
Also called Sterile buffered saline
This is the identical buffer solution in which H4:IC31 was formulated. The dose volume administered for Placebo was 0.5mL, and the mode of administration was an IM injection.
AERAS-404Biological
Also called H4:IC31
AERAS-404 vaccine was reconstituted on site by adding 0.2 mL H4 antigen solution to 0.8 mL IC31 adjuvant solution. The dose volume administered for AERAS-404 was 0.5mL, and the mode of administration was an IM injection.
| Study group | Role | What they receive |
|---|---|---|
| BCG SSI prime with Placebo | Placebo comparator | All subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42.
Placebo containing 0,8 mL sterile buffer consisting of 10 mmol Tris and 169 mmol NaCl aqueous solution was administered on Study Days 0, 56, and 231. Receives: Biological: BCG SSI; Biological: Placebo |
| BCG SSI prime with Placebo and AERAS-404 | Experimental | All subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42.
Placebo on Study Day 0 followed by AERAS-404 50/500 on Study Days 56 and 231.
AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows:
* H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3.
* IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. Receives: Biological: BCG SSI; Biological: Placebo; Biological: AERAS-404 |
| BCG SSI prime with AERAS-404 | Experimental | All subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42.
AERAS-404 50/500 on Study Days 0, 56, and 231.
AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows:
* H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3.
* IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. Receives: Biological: BCG SSI; Biological: AERAS-404 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of unsolicited, solicited, and serious adverse events (SAEs).
Includes injection site AEs and systemic AEs.
Measured: 259 days
Secondary outcomes (1)
Immunogenicity of BCG and a 2- or 3-dose regimen of AERAS-404 measured by intracellular staining assay (ICS).
ICS permits the detection of antigen-specific cytokine responses with a distinction between CD4+ and CD8+ T cells.
Measured: 259 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study startJan 2011
- Primary completionMay 2012
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi Pasteur, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Giuseppe Pantaleo, MD, Principal investigator, Centre Hosptialier Universitaire Vaudois (CHUV)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420444
- Sponsor's protocol ID
- C-013-404
- Acronym
- C-013-404
- Status last verified
- Jan 2017
- First submitted
- 15 Apr 2015
- Last updated
- 24 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of BCG and AERAS-404 Administered as a Prime-Boost Regimen to HIV-Negative, TB-Negative, BCG-Naive Adults
- ClinicalTrials.gov ID
- NCT02420444
- Acronym / sponsor ID
- C-013-404 / C-013-404
- Conditions
- Tuberculosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Sanofi Pasteur, a Sanofi Company
- Study start
- Jan 2011
- Primary completion
- May 2012 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 17 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.
70 subjects received BCG intradermally at Study Day -42, then at Study Day 0 were randomized to receive AERAS-404 50 mcg H4/500 nmol IC31 intramuscularly as a 3-dose (N=30) or 2-dose (N=30) regimen, or placebo (N=10). Subjects were vaccinated on Study Days 0, 56, and 231, and followed through Study Day 259.
Detailed description
A total of 70 subjects who had received BCG at Study Day -42 were randomized on Study Day 0 to receive 3 doses of placebo (N=10); 1 dose of placebo followed by 2 doses of AERAS-404 (N=30; AERAS-404 2 dose regimen); or 3 doses of AERAS-404 (N=30; AERAS-404 3 dose regimen). A total of 69 (98.6%) subjects completed the study; the remaining subject, in the AERAS-404 2 dose regimen, withdrew consent. All 70 subjects received the first and second vaccinations with placebo or AERAS-404 on Study Days 0 and 56, and 67 (95.7%) subjects received the third vaccination on Study Day 231. Three subjects did not receive the Study Day 231 vaccination (2 in the AERAS-404 2 dose regimen, 1 due to withdrawal of consent and 1 due to pregnancy [the subject delivered a healthy boy without complications and was followed to study completion]; and 1 in the AERAS-404 3 dose regimen, due to inability to discontinue daily isotretinoin started after the second vaccination [the subject was followed to study completion]).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BCG SSI prime with Placebo | Placebo comparator | Biological: BCG SSI, Biological: PlaceboAll subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42. Placebo containing 0,8 mL sterile buffer consisting of 10 mmol Tris and 169 mmol NaCl aqueous solution was administered on Study Days 0, 56, and 231. |
| BCG SSI prime with Placebo and AERAS-404 | Experimental | Biological: BCG SSI, Biological: Placebo, Biological: AERAS-404All subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42. Placebo on Study Day 0 followed by AERAS-404 50/500 on Study Days 56 and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. |
| BCG SSI prime with AERAS-404 | Experimental | Biological: BCG SSI, Biological: AERAS-404All subjects received BCG Vaccine SSI, 2-8 x 10^5 CFU (BCG) on Study Day -42. AERAS-404 50/500 on Study Days 0, 56, and 231. AERAS-404 50/500 was a fixed dose combination of H4 50 mcg and IC31 500 nmol (KLK equivalent). H4 and IC31 adjuvant were supplied as separate single-dose vials containing frozen product as follows: * H4 antigen: 500 mcg/mL (100 mcg/0.2 mL), in 10 mmol/L Tris-HCl, pH 8.3. * IC31 adjuvant: 1250 nmol/mL (1000 nmol/0.8 mL) KLK equivalent, in 10 mmol/L Tris-HCl and 169 mmol/L NaCl. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Had completed the written informed consent process.
- Was male or female.
- Was age ≥ 18 years and ≤ 50 years.
- Agreed to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and had no current plans to move from the study area for the duration of the study.
- Agreed to avoid elective surgery for the duration of the study.
Key exclusion criteria (29 listed)
- Oral temperature ≥37.5°C.
- Abnormal CBC laboratory values (per local laboratory parameters) from blood collected at screening (>5% above ULN or >5% below LLN).
- Abnormally elevated laboratory values (per local laboratory parameters) from blood collected at screening for ALT, AST, GGT, total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, prothrombin time (PT), or partial thromboplastin time (PTT) (>10% above ULN).
- Abnormal urinalysis that, in the opinion of the investigator, was clinically significant.
- Positive screening urine test for illicit drugs (opiates, cocaine, amphetamines).
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 |
|---|---|---|
| BCG SSIAlso: BCG Vaccine SSI Danish, bacillus Calmette-GuérinThe dose volume administered for BCG was 0.1 mL, and the mode of administration was ID injection to the deltoid area. | Biological | BCG SSI prime with AERAS-404, BCG SSI prime with Placebo, BCG SSI prime with Placebo and AERAS-404 |
| PlaceboAlso: Sterile buffered salineThis is the identical buffer solution in which H4:IC31 was formulated. The dose volume administered for Placebo was 0.5mL, and the mode of administration was an IM injection. | Biological | BCG SSI prime with Placebo, BCG SSI prime with Placebo and AERAS-404 |
| AERAS-404Also: H4:IC31AERAS-404 vaccine was reconstituted on site by adding 0.2 mL H4 antigen solution to 0.8 mL IC31 adjuvant solution. The dose volume administered for AERAS-404 was 0.5mL, and the mode of administration was an IM injection. | Biological | BCG SSI prime with AERAS-404, BCG SSI prime with Placebo and AERAS-404 |
Primary outcome
Number of unsolicited, solicited, and serious adverse events (SAEs).
Time frame: 259 days
Includes injection site AEs and systemic AEs.
1 secondary outcome
Immunogenicity of BCG and a 2- or 3-dose regimen of AERAS-404 measured by intracellular staining assay (ICS).
Time frame: 259 Days
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 24 Jan 2017.
- Individual participant dataSharing planned: Undecided
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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.
Giuseppe Pantaleo, MD principal investigator
Centre Hosptialier Universitaire Vaudois (CHUV)
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 BCG SSI and AERAS-404 in people with Tuberculosis, run by Aeras at 1 site in Switzerland.
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 9 inclusion and 29 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 24 Jan 2017. 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 Switzerland. 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?
Number of unsolicited, solicited, and serious adverse events (SAEs). (time frame: 259 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jan 2017.