Aeras Announces Results from Innovative Phase 2 Tuberculosis Vaccine Trial Offer Potential for New BCG Revaccination Strategies
Feb 19 18
Aeras announced results from an innovative clinical trial that provides encouraging new evidence that TB vaccines could prevent sustained infections in high-risk adolescents. In a prevention-of-infection Phase 2 trial conducted in South Africa, revaccination with the Bacille Calmette-Guerin (BCG) vaccine significantly reduced sustained TB infections in adolescents. An experimental vaccine candidate, H4:IC31, also reduced sustained infections, although not at statistically significant levels. However, the trend observed for H4:IC31 is the first time a subunit vaccine has shown any indication of ability to protect against TB infection or disease in humans. TB infections that developed during the study were determined using a QuantiFERON®-TB Gold in Tube (QFT-GIT) test, a commercially available blood test that helps diagnose TB infections. In the trial, individuals who tested negative for QFT-GIT were considered to not have a TB infection. The trial measured the rate by which individuals converted to QFT-GIT positive, implying evidence of TB infection. Those individuals who tested QFT-GIT positive consecutively over 6 months were considered to have a sustained infection. The results will be presented at the 5thGlobal Forum on TB Vaccines in New Delhi, India. The study evaluated H4:IC31 vaccination and BCG revaccination for safety, immunogenicity and the ability to prevent initial and sustained TB infections among healthy adolescents in the Western Cape Province of South Africa. H4:IC31 is an investigative subunit vaccine candidate being developed jointly by Aeras and Sanofi Pasteur, the vaccines business of Sanofi and the Statens Serum Institut. BCG is the only licensed tuberculosis vaccine available globally. The clinical trial was conducted at SATVI and at the Emavundleni Research Centre (part of the Desmond Tutu HIV Centre). It was funded by Sanofi Pasteur, the United Kingdom'sDepartment for International Development, The Bill & Melinda Gates Foundation and Aeras. The study was approved by the Medicines Control Council of South Africa and the relevant local independent ethics committees. The study involved 990 HIV-negative, healthy adolescents (12 to 17 years of age) who had been vaccinated as infants with BCG. All participants were randomized evenly into three study arms: placebo, H4:IC31, or BCG revaccination. All participants were screened to ensure they were not infected with Mycobacterium tuberculosis (Mtb) prior to vaccination in the study. At the outset of this innovative proof-of-concept study, statistical significance was set at one-sided p<0.1 to favor the risk of observing a false positive efficacy signal rather than a false negative. The data showed that both vaccines appeared to be safe and produced an immune response in the adolescents studied. No vaccine-related serious adverse events were reported in the study, and the most common vaccine-related adverse event was injection site swelling in BCG revaccinated participants, typical for BCG vaccination. For the primary efficacy endpoint, 134 participants tested positive for an initial Mtb infection as measured by QFT-GIT conversion from negative to positive (placebo=49; BCG=41; H4:IC31=44). When compared to placebo, neither vaccine achieved statistical significance in preventing an initial QFT-GIT conversion. Observed vaccine efficacy was 20.1% (p=0.15) for BCG revaccination and 9.4% (p=0.32) for H4:IC31. For the secondary efficacy endpoint, 82 participants exhibited a sustained QFT-GIT conversion lasting at least 6 months following initial conversion (placebo=36; BCG=21; H4:IC31=25). These participants were evaluated to see if they would revert to negative as measured by the QFT-GIT test. In the BCG revaccination arm, the vaccine efficacy for preventing a sustained infection was 45.4% (p=0.013) and in the H4:IC31 arm the vaccine efficacy was 30.5% (p=0.08).
Aeras Presents at VACCINES R&D-2017, Nov-14-2017 08:00 AM
Nov 13 17
Aeras Presents at VACCINES R&D-2017, Nov-14-2017 08:00 AM. Venue: Sheraton Reston Hotel, 11810 Sunrise Valley Dr, Reston, Virginia, United States. Speakers: Ann M. Ginsberg.