TuberculosisPhase 1/2C-015-404NCT01861730
Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants
A Phase 1/2 study testing AERAS-404 in people with Tuberculosis, run by Aeras at 4 sites in South Africa.
Trial summary
Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants. Read more about this study
- Who is it for?
- Ages 64 to 196 daysHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- AERAS-404
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 243 participants
- Where
- 4 sitesSouth Africa
- Study dates
- 1 Jul 2013to 22 Dec 2017
- Phase
- Phase 1/2
- 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 64 to 196 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age at time of entry:
- Cohorts 1 to 6
- Cohorts 1 and 2: ≥ 168 to ≤ 196 days
- Cohorts 3A and 3B: ≥ 168 to ≤ 189 days
- Cohorts 4 and 5: ≥ 84 to ≤ 98 days (≥ 2 weeks after receipt of EPI vaccine doses at 10 weeks of age)
- Cohort 6 - coincident with EPI vaccine doses at 10 weeks of age (≥ 64 to ≤ 83 days of age)
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- Source documentation of birth weight ≥ 2.5 kg.
- Documented BCG vaccination within 72 hours of birth.
- Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
- Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.
- Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.
- Parent or legal guardian able and willing to provide signed informed consent.
- Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.
Who cannot join
- History of TB exposure in household or non-household contact.
- History/Evidence of TB disease or infection.
- Quantiferon positive.
- Prior TST test.
- Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
- Receipt of a live vaccine within 28 days prior to randomization.
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- Receipt or planned receipt of any investigational vaccine.
- Known or suspected congenital immunodeficiency.
- Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
- Known or suspected autoimmune disease
- Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances as the vaccine used in the trial.
- Participation in another clinical trial for an investigational product (IP).
- Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
- Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) within 24 hours prior to randomization.
- Note: A subject may enroll after recovery from febrile illness if the subject is still within the age window.
- Systemic antibiotic use within 48 hours prior to randomization.
Trial locations and contacts
4 sites in 1 country.
South Africa4 sites
KID-CRU, Tygerberg Hospital
Cape Town, Tygerberg, 7505
PHRU, Chris Hani Baragwanath Hospital
Johannesburg, Guateng, 2091
Shandukani Research
Johannesburg, Hillbrow, 2001
South African TB Vaccine Initiative (SATVI)
Worcester
About this study
Official title: Phase 1/II, Safety and Immunogenicity Study of a Recombinant Protein Tuberculosis Vaccine (AERAS-404) in BCG-Primed Infants
Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants.
Read the detailed description
This is a Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study in HIV-uninfected, HIV-unexposed, BCG-primed infants. The study vaccine AERAS-404 or placebo will be administered without concomitant EPI vaccines (Cohorts 1 to 5, N = 159 subjects) and with concomitant EPI vaccines (Cohort 6, N = 70 subjects). Study vaccine or placebo will be administered as a single dose (injection) at Study Day 0 ( ≥168 to ≤ 196 days of age, Cohorts 1 and 2), a 2-dose schedule at Study Day 0 (≥ 168 to ≤ 189 days of age) and Study Day 28 (Cohorts 3A and 3B) or a 3-dose schedule at Study Day 0 (≥ 84 to ≤ 98 days of age), Study Day 42 and Study Day 98 (Cohorts 4 and 5). Subjects in Cohort 6 will receive the study vaccine or placebo at Study Day 0 (≥ 64 to ≤ 83 days of age), Study Day 28 (≥ 91 to ≤ 105 days of age), and Study Day 210 (≥ 273 to ≤ 287 days of age). A cohort will enroll once safety in the previous cohort has been established. AERAS-404 is an investigational vaccine manufactured by Sanofi Pasteur (SP) and Statens Serum Institute (SSI).
- 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 has two components: the H4 antigen and the IC31 adjuvant. The reconstitution of the vaccine components, H4 antigen (manufactured at SP) and IC31 adjuvant (supplied by SSI), will take place at the clinical research site (CRS) prior to injection.
PlaceboBiological
Also called Tris buffered saline
Tris buffered saline (10mM Tris, pH 7.4, 150nm sodium chloride).
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo | Experimental | 1 Dose; Subject ≥ 168 to ≤ 196 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo | Experimental | 1 Dose; Subject ≥ 168 to ≤ 196 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo | Experimental | 2 Doses; Subject ≥ 168 to ≤ 189 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo | Experimental | 2 Doses; Subject ≥ 168 to ≤ 189 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo | Experimental | 3 Doses; Subject ≥ 84 to ≤ 98 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo | Experimental | 3 Doses; Subject ≥ 84 to ≤ 98 days of age Receives: Biological: AERAS-404; Biological: Placebo |
| Cohort 6 AERAS-404 (dose level pending) or Placebo | Experimental | 3 Doses; Subject ≥ 64 to ≤ 83 days of age Receives: Biological: AERAS-404; Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited adverse events are captured 28 days post each vaccination. Evaluation of the safety profile of AERAS-404 will be performed using data from all subjects who received at least one dose and has 7 days of safety data, and will be summarized by cohort and treatment group. The number (percentage) of subjects with any adverse event (including solicited, unsolicited, and serious adverse events) will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and Preferred Term. Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine; parameters evaluable by the Aeras 404 Pediatric Toxicity Table provided in the protocol, will be summarized by severity corresponding to Toxicity Grade, as appropriate.
Measured: Subjects will be followed for up to 1 year and 4 months.
Secondary outcomes (1)
Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants
The number and percentage of subjects who are enrolled into the three-dose regimen (Cohorts 4-6) with solicited and unsolicited AEs (including serious adverse events [SAEs], local and systemic reactions, and clinical laboratory values or vital sign values recorded as newly abnormal following study vaccination) recorded post-vaccination will be summarized to address the secondary safety objective of the study. Subjects in Cohorts 4 and 5 will be followed for : 1 year and 3 months, Cohort 6: 1 year 4 months and Solicited adverse events are captured 28 days post each vaccination.
Measured: Subjects will be followed for up to 1 year and 4 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2013 (estimated)
- Study start1 Jul 2013
- Primary completion22 Dec 2017
- Study completion22 Dec 2017
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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeras
- Sponsor type
- University, hospital or other
- Collaborators
- Statens Serum Institut, Sanofi Pasteur, a Sanofi Company, National Institute of Allergy and Infectious Diseases (NIAID), International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Responsible party
- Sponsor
- Investigators
- Ann Ginsberg, MD, PhD, Study director, AerasAvy Violari, MD, Principal investigator, Perinatal HIV Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01861730
- Sponsor's protocol ID
- C-015-404/ IMPAACT P1113
- Other IDs
- U01AI068632, C-015-404
- Acronym
- C-015-404
- Status last verified
- Apr 2018
- First submitted
- 21 May 2013
- Last updated
- 9 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/II, Safety and Immunogenicity Study of a Recombinant Protein Tuberculosis Vaccine (AERAS-404) in BCG-Primed Infants
- ClinicalTrials.gov ID
- NCT01861730
- Acronym / sponsor ID
- C-015-404 / C-015-404/ IMPAACT P1113
- Conditions
- Tuberculosis
- Keywords
- BCG Vaccinated, HIV Negative
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 243 participants (actual)
- Lead sponsor
- AerasUniversity, hospital or other
- Collaborators
- Statens Serum Institut, Sanofi Pasteur, a Sanofi Company, National Institute of Allergy and Infectious Diseases (NIAID), International Maternal Pediatric Adolescent AIDS Clinical Trials Group
- Study start
- 1 Jul 2013 (actual)
- Primary completion
- 22 Dec 2017 (actual)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 24 May 2013 (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.
Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants.
Detailed description
This is a Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study in HIV-uninfected, HIV-unexposed, BCG-primed infants. The study vaccine AERAS-404 or placebo will be administered without concomitant EPI vaccines (Cohorts 1 to 5, N = 159 subjects) and with concomitant EPI vaccines (Cohort 6, N = 70 subjects). Study vaccine or placebo will be administered as a single dose (injection) at Study Day 0 ( ≥168 to ≤ 196 days of age, Cohorts 1 and 2), a 2-dose schedule at Study Day 0 (≥ 168 to ≤ 189 days of age) and Study Day 28 (Cohorts 3A and 3B) or a 3-dose schedule at Study Day 0 (≥ 84 to ≤ 98 days of age), Study Day 42 and Study Day 98 (Cohorts 4 and 5). Subjects in Cohort 6 will receive the study vaccine or placebo at Study Day 0 (≥ 64 to ≤ 83 days of age), Study Day 28 (≥ 91 to ≤ 105 days of age), and Study Day 210 (≥ 273 to ≤ 287 days of age). A cohort will enroll once safety in the previous cohort has been established. AERAS-404 is an investigational vaccine manufactured by Sanofi Pasteur (SP) and Statens Serum Institute (SSI).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo1 Dose; Subject ≥ 168 to ≤ 196 days of age |
| Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo1 Dose; Subject ≥ 168 to ≤ 196 days of age |
| Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo2 Doses; Subject ≥ 168 to ≤ 189 days of age |
| Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo2 Doses; Subject ≥ 168 to ≤ 189 days of age |
| Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo3 Doses; Subject ≥ 84 to ≤ 98 days of age |
| Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo3 Doses; Subject ≥ 84 to ≤ 98 days of age |
| Cohort 6 AERAS-404 (dose level pending) or Placebo | Experimental | Biological: AERAS-404, Biological: Placebo3 Doses; Subject ≥ 64 to ≤ 83 days of age |
Who may qualify
- Ages
- 64 to 196 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Age at time of entry:
- Cohorts 1 to 6
- Source documentation of birth weight ≥ 2.5 kg.
- Documented BCG vaccination within 72 hours of birth.
- Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
Key exclusion criteria (17 listed)
- History of TB exposure in household or non-household contact.
- History/Evidence of TB disease or infection.
- Quantiferon positive.
- Prior TST test.
- Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
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 has two components: the H4 antigen and the IC31 adjuvant. The reconstitution of the vaccine components, H4 antigen (manufactured at SP) and IC31 adjuvant (supplied by SSI), will take place at the clinical research site (CRS) prior to injection. | Biological | Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo, Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo, Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo, Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo, Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo, Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo, Cohort 6 AERAS-404 (dose level pending) or Placebo |
| PlaceboAlso: Tris buffered salineTris buffered saline (10mM Tris, pH 7.4, 150nm sodium chloride). | Biological | Cohort 1 Aeras404 (5ug H4/100nmol IC31) or Placebo, Cohort 2 AERAS-404 (5ug H4/500nmol IC31) or Placebo, Cohort 3A AERAS-404 (5ug H4/500nmol IC31) or Placebo, Cohort 3B AERAS-404 (15ug H4/500nmol IC31) or Placebo, Cohort 4 AERAS-404 (15ug H4/500nmol IC31) or Placebo, Cohort 5 AERAS-404 (50ug H4/500nmol IC31) or Placebo, Cohort 6 AERAS-404 (dose level pending) or Placebo |
Primary outcome
Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants.
Time frame: Subjects will be followed for up to 1 year and 4 months.
Adverse Events and Serious Adverse Events (SAE) will be collected on subjects throughout their participation in the study. Solicited adverse events are captured 28 days post each vaccination. Evaluation of the safety profile of AERAS-404 will be performed using data from all subjects who received at least one dose and has 7 days of safety data, and will be summarized by cohort and treatment group. The number (percentage) of subjects with any adverse event (including solicited, unsolicited, and serious adverse events) will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) system organ class and Preferred Term. Additional summaries will present the number (percentage) of subjects with any adverse events by severity and by relationship to study vaccine; parameters evaluable by the Aeras 404 Pediatric Toxicity Table provided in the protocol, will be summarized by severity corresponding to Toxicity Grade, as appropriate.
1 secondary outcome
Investigate the safety of a 3-dose AERAS-404 regimen in HIV-uninfected, HIV-unexposed, BCG-primed infants
Time frame: Subjects will be followed for up to 1 year and 4 months.
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 9 Apr 2018.
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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.
Ann Ginsberg, MD, PhD study director
Aeras
Avy Violari, MD principal investigator
Perinatal HIV Research Unit
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AERAS-404 in people with Tuberculosis, run by Aeras at 4 sites in South Africa.
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 13 inclusion and 17 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 9 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Africa. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Investigate the safety of AERAS-404 in HIV-uninfected, HIV-unexposed, BCG-primed infants. (time frame: Subjects will be followed for up to 1 year and 4 months.). 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 9 Apr 2018.