Clinical trials
Rigorous clinical trials in the field are vital to ensure the vaccine is safe and efficacious
Clinical trials are a critical step in developing a vaccine. Vaccine clinical trials assess primarily the safety of a new vaccine, its ability to induce an immune response, and its efficacy in human subjects. Trials may also assess how best to integrate the vaccine in existing healthcare systems, such as national immunization programs.
MVP coordinates vaccine trials with a wide range of partners to the highest scientific and ethical international standards, including the most recent version of International Conference on Harmonization guidelines for good clinical practice and the Declaration of Helsinki (external pdf, 101 kb).
Read more about the scientific and ethical review process used in MVP's clinical studies.
Vaccine clinical trials are commonly carried out in four phases. The trials at each phase have a different purpose and help scientists answer different questions, but occasionally phases may be merged in a single study, such as a study that includes a Phase 2/3 design.
Phase 1
Phase 1 clinical trials are principally designed to assess the safety and tolerability of the vaccine in humans. While Phase 1 trials do not have efficacy end points as primary objectives, they can also be used to evaluate the vaccine's ability to produce an immune response and to determine an appropriate dose range. These early trials usually involve 20–80 subjects who may be healthy volunteers, and they may last up to one year.
The MVP Phase 1 trial, PsA-TT-001, took place in India in 2005–2006 in 74 healthy adult volunteers. Read more about PsA-TT-001.
Phase 2
Phase 2 clinical trials are primarily designed to collect efficacy and immunogenicity data on the vaccine and to further evaluate vaccine tolerability and safety. Phase 2 trials typically involve up to several hundred volunteers who are followed up for two or more years.
MVP's first Phase 2 trial, PsA-TT-002, was carried out in Mali and the Gambia in 601 subjects aged between 12 and 23 months in 2006–2009. Read more about PsA-TT-002.
MVP's second Phase 2 trial, PsA-TT-004, was carried out in Ghana in 1,200 subjects aged between 14 and 18 weeks in 2008–2012. Read more about PsA-TT-004.
Phase 3
Phase 3 clinical trials typically have efficacy and immunogenicity as primary end points, but they are also used to confirm vaccine tolerability and safety on a large scale (from several hundred to several thousand participants).
MVP launched two Phase 2/3 trials in 2007. PsA-TT-003 enrolled 909 subjects aged between 2 and 29 years in Mali, Senegal, and the Gambia; while PsA-TT-003a enrolled 345 subjects aged 2 to 10 years in India. Read more about PsA-TT-003 and PsA-TT-003a.
MVP's first Phase 3 trial, PsA-TT-005, was completed in India on 830 subjects aged 5 to 10 years of age. MVP's second Phase 3 trial, PsA-TT-006, enrolled 6,000 subjects aged between 1 and 29 years in Mali. MVP's third Phase 3 trial, PsA-TT-007, was completed in Mali on 1,500 participants aged 9 to 12 months. It was the last MVP clinical trial. Read more on PsA-TT-005, PsA-TT-006, and PsA-TT-007.
If Phase 3 results confirm vaccine safety, immunogenicity, and efficacy, the manufacturer applies to regulatory authorities for permission to license and market the product.
It is worth noting that in some cases, vaccines can be licensed without a full Phase 3 efficacy study. For instance, in 1999 regulatory authorities in the United Kingdom licensed three group C meningococcal conjugate vaccines based on safety and immunogenicity data, without a Phase 3 efficacy study. More recently in 2005, a meningococcal tetravalent conjugate vaccine (Menactra®) was licensed in the United States on the basis that it was not inferior to a meningococcal polysaccharide vaccine in terms of immunogenicity and safety. This is the strategy that has been followed for MenAfriVac®, the meningococcal A conjugate vaccine, as Serum Institute of India Ltd applied for vaccine licensure in the summer of 2009, based on safety and immunogenicity data from Phase 1, Phase 2, and Phase 2/3 studies.
Phase 4
Phase 4 clinical trials, also referred to as "postmarketing studies," are conducted after the vaccine has been marketed and gather additional information on any rare, serious adverse reaction or side-effect that had not been detected during Phases 1, 2, and 3, and on the vaccine's effects in various populations—i.e., the trial examines the protection it confers to vaccinees (direct effect), to non-vaccinees (indirect effect), and to the community overall (herd immunity). Phase 4 studies look at durability of protection and vaccine effectiveness—i.e., how well the vaccine works in real field conditions, as opposed to how well it works in clinical trials (efficacy). Phase 4 studies may last four to six years.
Three safety studies done after field use of about 1.1 million doses of MenAfriVac® in the fall of 2010 did not identify any safety concerns with the vaccine; and postmarketing data obtained since the December 2010 official launch of MenAfriVac® in Africa continue to indicate the vaccine is very safe and highly effective.