NEW DELHI, Feb. 19, 2018 /PRNewswire-USNewswire/ -- Aeras, a
nonprofit organization dedicated to developing vaccines against
tuberculosis (TB), today 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 5th Global Forum
on TB Vaccines in New Delhi,
India.
According to the World Health Organization (WHO), about
one-third of the world's population has what is called a latent TB
infection, which means people have been infected by TB bacteria but
are not (yet) ill with the disease and cannot transmit the disease.
People infected with TB bacteria have a lifetime risk of falling
ill with TB of 10 percent. People ill with TB can infect 10–15
other people through close contact over the course of a year.
Without proper treatment, 45% of HIV-negative people with TB on
average and nearly all HIV-positive people with TB will die.
Mark Hatherill, MD, Director of
the South African Tuberculosis Vaccine Initiative (SATVI) at the
University of Cape Town, and the
study's principal investigator, said: "We are pleased to have
performed the first-known randomized, placebo-controlled
prevention-of-infection trial for TB and to have demonstrated that
vaccination has the potential to reduce the rate of sustained
TB infection in a high-transmission setting. While neither vaccine
proved to be statistically significant in preventing an initial TB
infection, we are extremely encouraged by the signals observed for
both vaccines in preventing sustained TB infections. We believe the
results from this novel trial design will provide significant
scientific benefit to the field in understanding TB infection, and
based on this positive signal, we look forward to testing the
potential of such vaccines to prevent TB disease among uninfected
adolescents in a larger, more traditional prevention-of-disease
clinical trial."
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 (EURONEXT: SAN) (NYSE: SNY), 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's Department 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.
Linda-Gail Bekker, MD, PhD, a
lead investigator for the trial, the Chief Operating Officer at the
Desmond Tutu HIV Foundation and President of the International AIDS
Society, said: "We would like to thank all the study participants
and their families for participating in this novel clinical trial.
We believe the results are important and warrant further
investigation into other subunit vaccines and a reevaluation of BCG
revaccination as a potential strategy to prevent TB in
high-incidence countries. An effective TB vaccine remains an urgent
global goal."
Jacqui Shea, PhD, CEO of Aeras,
stated: "New TB vaccines are essential to end this deadly epidemic,
especially with the rise of drug-resistant strains. In this
innovative study, we not only observed important results for BCG,
we also saw the first early efficacy signal against infection to be
shown by a subunit TB vaccine candidate (H4:IC31). Further, we
established that the novel prevention-of-infection trial design has
the potential to provide evidence of a biological signal earlier
and at lower cost than traditionally designed TB vaccine prevention
of disease efficacy studies. The data collected will inform the
next series of clinical studies as well as enable the search for
correlates of protection against sustained infection. Later this
year, Aeras and its partners look forward to announcing primary
results from a Phase 2b prevention of
disease trial with M72/AS01E, another subunit vaccine candidate,
and to commencing two Phase 2 clinical trials with an additional,
promising subunit vaccine candidate."
Study Design and Results for H4:IC31 Vaccination and BCG
Revaccination
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).
About TB and Vaccine Development
Tuberculosis is designated a priority infectious disease by the WHO
(www.who.int/tb/en/). It causes more deaths than any other single
infectious disease and is increasingly characterized by
antimicrobial resistance. There were 10.4 million new cases of TB
in 2016 and 1.7 million deaths.
Introduced in 1921, BCG is the only vaccine currently licensed
to prevent TB disease. Past observational studies have indicated
that primary BCG vaccination may offer partial protection against
initial Mtb infection. It has also been hypothesized that
revaccination with BCG might provide additional protection against
Mtb infection. However, prior to this proof-of-concept trial, this
hypothesis had not been tested in a prospective, randomized,
placebo-controlled trial. The results presented at the
5th Global Forum on TB Vaccines indicating that
sustained QFT-GIT conversions are preventable by BCG revaccination
provide novel insights into possible mechanisms of protection in
humans. These results are consistent with the hypothesis that
vaccine-induced immune responses may increase the ability to
control or clear an Mtb infection.
About Aeras
Aeras is a nonprofit organization advancing the development of new
tuberculosis vaccines for the world in partnership with other
biotech, pharmaceutical and academic organizations. Aeras is
primarily funded by The Bill & Melinda Gates Foundation, the UK
Department for International Development (DFID), and other parties
committed to ending the TB epidemic. Aeras also receives support
from the U.S. government and through partnerships and
collaborations with universities and pharmaceutical companies
around the world. Aeras is headquartered in Rockville, Maryland (USA), with a clinical
development and operations office in Cape
Town, South Africa. For more information, please visit
www.aeras.org.
About Sanofi
Sanofi is dedicated to supporting people through their health
challenges. We are a global biopharmaceutical company focused on
human health. We prevent illness with vaccines, provide innovative
treatments to fight pain and ease suffering. We stand by the few
who suffer from rare diseases and the millions with long-term
chronic conditions.
With more than 100,000 people in 100 countries, Sanofi is
transforming scientific innovation into healthcare solutions around
the globe.
About Statens Serum Institut (SSI)
SSI is under the auspices of the Danish Ministry of Health. Its
main duty is to ensure preparedness against infectious diseases and
biological threats as well as control of congenital disorders.
About South African Tuberculosis Vaccine Institute (SATVI)
SATVI is a world leader in TB vaccine clinical research located
within the Health Sciences Faculty at the University of
Cape Town. The goal of SATVI is
the development of new and effective vaccination strategies against
TB through conduct of clinical trials of new vaccine candidates and
immunology studies to better understand risk for and protection
against TB. For more information visit www.satvi.uct.ac.za.
About Desmond Tutu HIV Foundation
The Desmond Tutu HIV Foundation, housed within the Desmond Tutu HIV
Centre at the University of Cape
Town, is committed to the pursuit of excellence in research,
treatment, training and prevention of HIV and related infections in
South Africa.
Fully self-funded by grants and other investigator raised funds,
its vision for the future includes the continuation of current
TB/HIV related work of treatment, care, prevention and education
particularly in the most vulnerable populations, whilst staying
abreast of new developments and continuing to contribute to cutting
edge information in HIV and TB public health, social and clinical
research.
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