Common Questions

What happens in a Phase 3 vaccine trial?

A Phase 3 vaccine trial tests the candidate in tens of thousands of people against a placebo, measuring how well it prevents infection or disease, whether it is SAFE at scale, and how the immune response varies across different populations. Regulators use Phase 3 results to decide whether to approve the vaccine.

Why is an H5N1 Phase 3 trial being run before a pandemic?

Running Phase 3 before an H5N1 pandemic means regulators will have existing safety and immunogenicity data when they need to authorise a vaccine rapidly. Without pre-pandemic Phase 3 data, emergency authorisation within 100 days of a pandemic declaration would be nearly impossible.Source: CEPI

Does Phase 3 data from one H5N1 strain protect against a different pandemic strain?

Not automatically. If a pandemic H5N1 strain diverges significantly from the Phase 3 trial construct, regulators would require bridging studies comparing the new strain's immunogenicity against the trial data. The value of pre-pandemic Phase 3 is in reducing the lead time for those bridging studies, not in guaranteeing direct cross-protection.Source: CEPI

Background

Phase 3 is the third and final stage of the standard clinical trial sequence used by regulators worldwide before approving a vaccine or therapeutic. In a Phase 3 vaccine trial, the candidate is tested in a large population, typically tens of thousands of participants, against placebo or comparator, to measure efficacy against infection or disease, safety at scale, and immunogenicity across diverse demographic subgroups. Phase 3 results form the core of a regulatory submission to agencies such as the FDA, EMA, or MHRA. Emergency Use Authorisation pathways allow Phase 3 data to be reviewed on accelerated timelines during a declared public health emergency, as occurred with COVID-19 vaccines in 2020.

Moderna's mRNA H5N1 candidate entered Phase 3 on 22 April 2026, the first H5N1 mRNA vaccine to reach this stage, in a trial announced by CEPI as the 100 Days Mission's first practical test. Running Phase 3 before a pandemic strain emerges inverts the conventional trial sequence; the standard model requires enough human disease to enrol a placebo-controlled efficacy study, which by definition cannot happen until a pandemic has begun. Pre-pandemic Phase 3 design instead collects immunogenicity and safety data against a pre-selected antigen, with bridging studies planned for once a pandemic strain is identified. The principal regulatory question is whether pre-existing Phase 3 data on one H5N1 antigen constitutes sufficient evidentiary basis for emergency authorisation against a divergent pandemic strain.

Source Material

CEPI vaccine portfolio Phases of clinical research — Wikipedia

How the World Sees Them

Global South

Lower-income countries note that Phase 3 in a high-income trial context does not necessarily validate the vaccine for diverse global populations; WHO prequalification and regional regulatory review remain additional steps for GAVI-eligible countries.

Pharmaceutical industry

Manufacturers value pre-pandemic Phase 3 because it resolves the commercial risk of investing in a pandemic product: CEPI financing covers the trial cost and the resulting data de-risks any emergency manufacturing commitment.

Regulatory agencies (FDA/EMA)

Regulators view pre-pandemic Phase 3 data as a necessary but not sufficient basis for emergency authorisation; bridging studies matching the pandemic strain will still be required, but they can be completed in weeks rather than months.