LONDON – Companies represented in the expert group brought together by the World Health Organization (WHO) to work on the development of COVID-19 vaccines have signed a pledge to strengthen collaboration and sharing of data.
In a declaration on WHO’s website, companies including Sanofi SA, Moderna Inc., Inovio Inc., Clover Biopharmaceuticals Inc., Cansino Biologics Inc., Curevac AG and Novavax Inc., which have some of the most advanced vaccine candidates, say they will continue efforts to strengthen the “unprecedented” cooperation, “to help reduce inefficiencies and duplication of effort.”
The declaration also is signed by academic groups developing vaccines and by drug regulators, funding agencies and scientists from around the world.
The statement was published as WHO released the draft design for the Solidarity vaccines trial. It is intended that the large, international randomized study will enable the concurrent evaluation of the benefits and risks of each candidate vaccine within three to six months of it being available for testing.
WHO’s landscape analysis of vaccines in development lists 70 products, of which Cansino, Moderna and Inovio’s have advanced to phase I.
A WHO spokesman said the adaptive design of the Solidarity trial will allow products to be added at any time. “Candidate vaccines may be added to the trial as they become available if they meet prioritization criteria, to be defined via the WHO vaccine prioritization group,” he told BioWorld.
For reference, WHO also released a target product profile, setting out the criteria products should meet.
Randomization in the study will be managed centrally, so that each participant has the same chance of receiving a placebo as they have of receiving each individual vaccine.
WHO said the trial design is “consistent with the collaborative spirit” underlying COVID-19 vaccine development, and will “foster international deployment with equity of access.”
In comparison with conducting separate trials, evaluating products in parallel increases the likelihood that a participant will receive a vaccine candidate. At the same time as improving the efficiency of the study, that will promote better use of clinical trial resources worldwide.
In addition, the scale of the trial reduces uncertainties about endpoints and increases the likelihood of enrolling enough participants to rapidly assess the efficacy of each vaccine.
That also will make it possible to rank the relative efficacy of different products, increasing the risks for their developers.
On the other hand, the chance to join an ongoing trial, with sites up and running, will reduce companies’ costs.
WHO is appealing for $4.74 million to accelerated priority research and innovation in developing vaccines for COVID-19. “This resource requirement does not include the costs associated with the actual development, manufacturing, testing, and licensing of research and development products,” the spokesman said.
Choice of sites
Any site with “sufficient” transmission rates of COVID-19 at the time of entering the trial will be able to participate. The primary outcome will be confirmed COVID-19 infection, regardless of severity. The number of confirmed infections for each vaccine will be compared to the infection rate for all patients in the placebo arm.
Secondary endpoints will include severity of disease, immunogenicity and viral shedding.
Follow-up will involve weekly contact, with the study remaining blinded for up to one year, unless a vaccine appears to be protective, when unblinding could be sooner.
The trial will be overseen by a steering committee, which will remain blinded to the data, and a data monitoring committee.
WHO has applied a similar adaptive design to the assessment of potential therapies against COVID-19, promising to reduce the time taken to deliver results by 80%, compared to standard trials.
As of April 9, more than 90 countries are participating in the study, which is testing remdesivir, the HIV combination drug lopinavir/ritonavir, interferon beta 1, and chloroquine or hydroxychloroquine (depending on which a hospital has available).
A central computer randomly allocates consented patients to one of the arms.
The speed with which centrally controlled studies can recruit patients is illustrated by the U.K. Recovery trial, which also is testing approved drugs as potential therapies. Since getting underway three weeks ago, the study has recruited 4,513 patients at 161 sites.
Patients admitted to hospital with a suspected or confirmed COVID-19 infection are invited to participate. To reduce the amount of bureaucracy for hard-pressed health care workers, consent forms have been slimmed down. As with the WHO trial, a central system, run from Oxford University, allocates patients to one of the active arms or control.
Initially the study was evaluating lopinavir/ritonavir, interferon beta 1, and hydroxychloroquine, but now the antibiotic azithromycin has replaced interferon-beta, while an inhaled formulation of interferon-beta is being tested in a separate trial.
It is hoped that by enrolling a large number of patients it will be possible to identify benefits that may be modest, but can improve overall outcomes. Endpoints are death and the need for ventilation.
The need for such large trials was underlined when Gilead Sciences Inc. announced results from a cohort of 53 COVID-19 patients who received remdesivir on a compassionate use basis. While there were indications of positive effects, the company said data from randomized phase III trials is needed to provide a scientifically robust understanding of the clinical impact of remdesivir treatment.