Tuberculosis Clinical Trial
Official title:
A Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents
Verified date | May 2019 |
Source | Aeras |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection with Mycobacterium tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents
Status | Completed |
Enrollment | 989 |
Est. completion date | October 6, 2017 |
Est. primary completion date | August 28, 2017 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 12 Years to 17 Years |
Eligibility |
Inclusion Criteria: 1. Has completed the written informed consent and assent process 2. Is age = 12 years and = 17 years on Study Day 0 3. Agrees to stay in contact with the study site for the duration of the study, provide updated contact information 4. For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and for the full duration of the study. 5. Has general good health, confirmed by medical history and physical examination 6. Had BCG vaccination at least 5 years ago documented through medical history or by presence of healed BCG scar 7. Tests QFT-GIT negative at screening, using the manufacturer's recommended threshold of 0.35 IU/mL Exclusion Criteria: 1. Acute illness on Study Day 0 2. Oral temperature =37.5°C on Study Day 0 3. Clinically significant (and no more than Grade 1 on the Toxicity Scale) abnormal laboratory values from blood collected within 21 days 4. Evidence of clinically significant (and no more than Grade 1 on the Toxicity Scale) systemic or local disease on urinalysis 5. History or evidence of any clinically significant systemic disease, or any acute or chronic illness that might affect the safety, immunogenicity, or efficacy of study vaccine in the opinion of the investigator 6. History of treatment for active TB disease or latent Mtb infection 7. History or evidence, including chest X-ray, of active TB disease 8. Shared residence with an individual receiving anti-TB treatment, or known incompletely treated culture or smear positive TB 9. History of autoimmune disease or immunosuppression 10. Used immunosuppressive medication within 42 days before Study Day 0 11. Received immunoglobulin or blood products within 42 days before Study Day 0 12. Received any investigational drug therapy or investigational vaccine within 182 days before Study Day 0 13. Received investigational TB vaccine, other than BCG 14. Planned administration/administration of a licensed vaccine in the period starting 28 days before and ending 28 days after each dose of study vaccine 15. History or laboratory evidence of any past or present possible immunodeficiency state not limited to any lab indication of HIV-1 infection 16. History of allergic disease likely to be exacerbated by any component of the study vaccine 17. History of alcohol or drug abuse 18. All female subjects: currently pregnant or lactating/nursing; or positive urine pregnancy test during screening 19. Received a (TST) within 3 months (90 days) prior to Study Day 0. 20. Any current medical, psychiatric, occupational, substance abuse problems problems that in opinion of investigator will make unlikely for the subject to comply with the protocol |
Country | Name | City | State |
---|---|---|---|
South Africa | South African Tuberculosis Vaccine Initiative , Project Office, Brewelskloof Hospital , Harlem Street, Worcester | Cape Town | Western Cape |
South Africa | Desmond Tutu HIV Foundation (DTHF) | Nyanga |
Lead Sponsor | Collaborator |
---|---|
Aeras | Sanofi Pasteur, a Sanofi Company |
South Africa,
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Ho — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety Profile of H4:IC31 and BCG Revaccination in HIV-uninfected, Remotely BCG Vaccinated Adolescents. | Number of unsolicited and solicited adverse events recorded post vaccination. Unsolicited adverse events: 28 days post each vaccination Solicited adverse events: 7 days post each vaccination (with diary cards used for 7 days after each vaccination for Safety and Immunogenicity Cohort only) Solicited and unsolicited injection site reaction adverse events: BCG Group - 84 days post vaccination; H4:IC31/Placebo Groups - 28 days post each vaccination Serious adverse events, adverse events of special interest, and SUSARs: Entire study period, with a minimum of 6 months following the last dose of study vaccine |
Study day 7 thru 6 months after last vaccination | |
Primary | Number of Participants Testing Positive for Mtb at Day 84 | Rates of conversion to Mtb-positive measured by QuantiFERON-TB Gold In-tube (QFT-GIT) assay. The primary evaluation of Mtb infection was QFT-GIT conversion from a negative to positive test, using the manufacturer's recommended threshold of =0.35 IU/mL, at any time point after Day 84 and through end of follow-up for the primary endpoint. All participants with primary QFT-GIT conversion were followed for an additional 6 months post-conversion to ascertain the sustained QFT-GIT conversion and QFT-GIT reversion endpoints. Participants with an initial QFT-GIT conversion at Month 6 or 12 were asked to return for a final QFT-GIT evaluation and assessment for TB signs and symptoms at least 24 months after their initial vaccination. H4:IC31 compared to placebo BCG revaccination compared to placebo |
Study day 84 through 6 months post-conversion | |
Secondary | Rates of Sustained Conversion to Mtb-positive | Rates of sustained conversion to Mtb-positive as measured by QFT-GIT assay. H4:IC31 compared to placebo BCG revaccination compared to placebo |
6 months after initial conversion | |
Secondary | Percentage of Participants With Immune Response to Vaccine in HIV-uninfected, Remotely BCG-vaccinated Adolescents: o H4:IC31 o BCG Revaccination | A 13 color intracellular cytokine staining assay (ICS) was performed on peripheral blood mononuclear cells (PBMC) to assess CD4+ T cells that expressed IFN-?, TNF, IL-2, IL-17, IL-22, CD107a, and/or CD154 alone or in combination in response to stimulation with peptide pools representing the entire amino acid sequence of the TB mycobacterial antigens Ag85B and TB10.4, and BCG antigens. Responders were IFN-gamma and/or IL-2 positive. An intracellular cytokine assay was performed on whole blood (WB) to measure the frequencies and patterns of CD4+ T cells expressing Th1 and Th17 cytokines following stimulation of whole blood with peptide pools representing the entire amino acid sequence of the TB mycobacterial antigens Ag85B and TB10.4, as well as viable BCG from the vaccine vial. Responders were IFN-gamma, IL-2, TNF, IL-17, and/or IL-22 positive. |
Study day 70 |
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