Crucell and the Aeras Global TB Vaccine Foundation today announced the start of a Phase II clinical trial of the jointly developed tuberculosis (TB) vaccine candidate AERAS-402/Crucell Ad35 in HIV infected adults.
The Phase II study is designed to test the safety and efficacy of AERAS-402/Crucell Ad35 in adults infected with HIV and will be conducted by the Aurum Institute in Klerksdorp, South Africa.
All Aeras-sponsored TB vaccine candidates have been or will be tested for safety in people living with HIV. Among people living with HIV in Africa and Asia, TB is a leading cause of death. People with HIV living in countries with high TB prevalence are 20 times more likely to develop TB than those who are HIV-negative.
According to the World Health Organization's (WHO) 2009 TB surveillance report, one in four TB deaths globally is HIV-related, twice as many as previously recognized. In 2007, there were an estimated 1.4 million new cases of TB among people living with HIV and 456 000 deaths. Seventy-one percent of people with TB in South Africa are co-infected with HIV.
"With the support of Crucell's innovative technologies, we are on a joint mission with Aeras to develop a next generation vaccine against TB," said Dr. Jaap Goudsmit, Crucell's Chief Scientific Officer. "As there are many potential uses of the new TB vaccine, it is crucial to test the safety and immune responses in those who have been infected with HIV. That is why we are extremely pleased with the initiation of this Phase II study, an important next step towards our ambition of reducing the global burden of this fatal disease."
Enrollment of study volunteers for the first stage of the Phase II trial has started. This is the first study testing the AERAS-402/Crucell Ad35 TB vaccine candidate among this study population.
In 2004, Aeras and Crucell began jointly developing this vaccine candidate using Crucell's AdVac vaccine technology and PER.C6 manufacturing technology. Data from all AERAS-402/Crucell Ad35 trials support the immunogenicity and acceptable safety profile of the TB vaccine candidate at all dose levels evaluated.
AERAS-402/Crucell Ad35 trials
In October 2008, the first Phase II study in adults who have had active TB started in South Africa. In this ongoing study, AERAS-402 has demonstrated an acceptable safety profile. Preliminary data indicate that the candidate vaccine induces CD8-cell immune responses in patients who have completed TB treatment.
To date, seven Phase I studies have been conducted in populations including healthy adults and infants and adult tuberculosis patients:
- A trial in healthy adults not previously immunized with Bacille Calmette-Guérin (BCG), the traditional TB vaccine, demonstrated that the candidate vaccine had an acceptable safety profile in this population.
- A South African study showed CD8 T cell immune responses that are much higher than those seen in humans in any previous TB vaccine study.
- US studies in healthy adults, focusing on the immunogenicity and safety of two boost doses after BCG priming, showed that two injections of the candidate vaccine are immunogenic, with an acceptable safety profile, when used in combination with a BCG prime, regardless of the boosting interval. This immune response is greater than that detected in the absence of BCG prime, supporting the possible utility of AERAS-402/Crucell Ad35 as a booster vaccine. BCG prime alone shows limited efficacy.
- Testing of the candidate vaccine's safety in BCG-vaccinated adults with or without latent TB has been completed in Kenya, with ongoing analysis. The vaccine had an acceptable safety profile in this study.
- A trial in South Africa is testing the safety of the candidate vaccine in infants previously vaccinated with BCG vaccine. The study is fully enrolled and dosing is ongoing. To date, the vaccine appears to have an acceptable safety profile in this study.
- Currently a US trial has started for more detailed analysis of the immune response to AERAS-402/Crucell Ad35, using a known immunogenic regimen of BCG and the candidate vaccine in healthy adults, followed by collection of large numbers of immune cells.
Press release issued by Crucell and Aeras Global TB Vaccine Foundation, April 14 2010.