The randomized, observer blind, placebo-controlled Phase 2b/3 trial called HERALD will assess the safety and efficacy of CVnCoV in subjects 18 years or older at a dose of 12 micrograms.
The study is expected to include more than 35,000 participants at sites in Europe and Latin America, said the Tübingen, Germany headquartered company.
"CureVac intends to initiate a rolling submission with the European Medicines Agency (EMA) in the first quarter of 2021 based on initial analysis of data from the pivotal study," a spokesperson for the German biotech told BioPharma-Reporter.
CureVac’s vaccine is based on the same mRNA technology as the COVID-19 vaccine candidates developed by BioNTech/Pfizer and Moderna.
"With the start of the pivotal Phase 2b/3 study, we have reached another important milestone in the development of our vaccine candidate, CVnCoV," said Dr Franz-Werner Haas, CEO of CureVac. "The clinical safety and immunogenicity data achieved to date look promising and we are hopeful that this trial will continue to demonstrate the impact of mRNA technology and our vaccine to prevent COVID-19, and to help defeat this pandemic."
Study design
The company said the HERALD trial will start with an initial Phase 2b part, which is expected to seamlessly merge into a Phase 3 efficacy trial. Subjects will be enrolled at multiple sites and will receive a two-dose schedule of either SARS-CoV-2 or placebo.
Besides the primary safety objective, the study design includes two primary efficacy objectives: the demonstration of the efficacy of CVnCoV in preventing first episodes of confirmed cases of COVID-19 of any severity, as well as preventing moderate to severe confirmed cases of COVID-19 in participants who have never been infected with SARS-CoV-2, said the developer
Efficacy of CVnCoV will be assessed by an event-driven analysis based on a certain number of participants who present with laboratory confirmed symptomatic COVID-19 disease during the study. To ensure continued and close safety monitoring of the participants in the trial, data will be reviewed by an independent Data Safety Monitoring Board on a regular basis, said the company.
Following completion of the trial, it said subjects will continue to be monitored in a one-year extension study. The extension study will collect additional data to evaluate long-term safety, persistence of antibodies to SARS-CoV-2 and the occurrence of COVID-19 cases to assess the duration of vaccine efficacy.
Cold chain distribution benefits, manufacturing strategy
Last month, CureVac announced that, following testing, it found that CVnCoV was suitable for standard refrigeration and the current cold chain distribution channels. In addition, it reported that its vaccine remains stable for at least three months at +5°C (+41°F) and up to 24 hours as a ready-to-use vaccine when stored at room temperature.
That same month saw the EU Commission reach an agreement with CureVac for up to 405 million doses of its COVID-19 vaccine.
Also announced in November was the deal CureVac signed with Wacker Chemie around the manufacture of CVnCoV. Under the terms of that agreement, Wacker will ramp up GMP production of the mRNA drug substance for CVnCoV at its biotech site in Amsterdam in the first half of 2021. Preparations for the start of production, technology transfers and test runs are already underway.
CureVac said the plan is to produce more than 100 million doses of the CVnCoV per year at Wacker’s Amsterdam site. There is also further potential for expansion at the site in order to meet rising demand in the future, it added.
CureVac is building an integrated European vaccine manufacturing network with several CDMO partners. With this strategy, the company is expecting to significantly increase its existing manufacturing capacities for CVnCoV to up to 300 million doses in 2021 and up to 600 million doses in 2022, while managing potential supply chain risks.
"Geographic proximity is an important factor for facilitating alignment and technology transfers,” said Florian von der Mülbe, CureVac’s chief production officer, in a release.
An additional large-scale production facility supported by the European Investment Bank (EIB) at CureVac's HQ in Tübingen is currently in development. The EIB financing of €75m (US$89m) will be provided in three €25m tranches upon completion of pre-defined milestones.
