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Therapeutics Clinical Working Group
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Charge
Prioritize therapeutic agents for testing within an adaptive master protocol strategy that will be jointly designed by the partnership and quickly launched in networks identified by the Clinical Trial Capacity Working Group.
Objectives
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✓ Agent Prioritization
The working group developed a process (see image below) to prioritize clinical agents for rapid testing:
An overview of the sources used to identify agents for prioritization in the ACTIV master protocols. The clinical therapeutics fall into four categories (antivirals, immunomodulators, supportive therapies, and neutralizing antibodies). The activities of the prioritizations team is also described as refining the process and criteria, scoring the candidates, and assessing logistical needs.
Wave 1
- Using publicly available sources, approximately 400 candidate agents were identified. Compounds already FDA-approved were the focus to allow for quick repurposing to treat patients. An agent prioritization review committee selected by the working group used an agent triage process to narrow the list to 39 therapeutic candidates. Prioritizing the most promising candidates not already in existing clinical trials was also a focus in order to maximize the number of therapeutic agents in development to ultimately find successful treatments.
- Using a rigorous set of prioritization criteria and a scoring system developed by the working group, the 39 candidates were split into four groups (antivirals, host targeted therapies/immune modulators, and symptomatic/supportive therapies) and scored to determine prioritization for deployment in master protocols.
- Following a final prioritization review, the most promising agents were identified to move into clinical testing.
Wave 2 and Beyond
The prioritization process was refined, tailored to each therapy class, and applied to additional therapies submitted through the ACTIV Clinical & Preclinical Candidate Compound Survey. In addition, a new agent prioritization sub-team was formed to analyze neutralizing monoclonal and polyclonal antibodies; new prioritization criteria were developed specifically for these neutralizing antibody candidates.
An overview of the actual steps in the evaluation process that generates the final list of highly promising therapeutics for testing in the ACTIV master protocols. Each step acts as a gate for the next step and leads to either more detailed consideration or removal from consideration. The types of questions that need to be addressed are shown to be related to current status in human clinical trials, efficacy data in COVID-19 treatment, and other more detailed criteria (for example human delivery data or manufacturing issues). The process that ends in initiation of the therapeutic in an ACTIV master protocol is a reproducible, scientific, data-driven process.
Based on the results of the first and subsequent waves of agent prioritization, ACTIV clinical trials are now underway.
✓ Clinical and Preclinical Candidates Survey
To assist in developing and prioritizing a complete inventory of potential candidates with different approaches to preventing or mitigating COVID-19 infection, ACTIV created a Clinical & Preclinical Candidate Compound Survey in conjunction with the Preclinical Working Group. The survey collected detailed information, such as preclinical and clinical data, on therapeutic candidates. ACTIV is no longer accepting submissions for clinical and preclinical candidate compounds.
Master Protocols for Therapeutics
The working group has assessed and designed multiple master protocols for ACTIV clinical trials, as well as selected clinical trial networks for these protocols. Using master protocols allows for the standardization of primary endpoints to enable the comparison of trial data, as well as the customization of secondary endpoints appropriate for each trial. ACTIV master protocols have been designed with a portfolio approach in mind and are intended to test all classes of agents in and appropriate patient population and setting, including immunomodulators, anticoagulants, antivirals, and neutralizing monoclonal antibodies.
Six master protocols to test the agents selected through the above prioritization process were designed (ACTIV-1, -2, -3, -4, -5, and -6); these are described further on the ACTIV Therapeutics Page. View the clinical trial sites participating in the ACTIV master protocols.
Members
This page last reviewed on November 20, 2023