2022-11-15-世界卫生组织-Solidarity_Trials_Core_Protocol_-_Randomized_trial_to_evaluate_the_efficacy_and_safety_of_select_therapeutic_agents_in_the_treatment_of_Ebola_Disease_41页_665kb

SOLIDARITY TRIALS: Ebola Disease Therapeutics CORE Protocol Summary

This summary outlines the key elements of the SOLIDARITY Ebola Disease CORE Protocol.

Overview

• Trial Type: Adaptive, platform, randomized controlled clinical trial.
• Purpose: To evaluate the efficacy and safety of therapeutic agents for Ebola Disease caused by Zaire (EBOV) and Sudan (SUDV) Ebolaviruses.
• Mechanism: Co-sponsored by the World Health Organization (WHO) and the Uganda Ministry of Health. Coordinated via a central office. Funded by WHO.

Key Context

• Previous successful therapies (REGN-EB3, MAB114) target EBOV and are ineffective against SUDV.
• No approved therapies for SUDV exist.
• Protocol designed as a "platform" to potentially adapt treatments (add/remove arms) based on evolving evidence and outbreak needs.
• Current implementation focuses on Uganda due to the SUDV outbreak.

Study Design

• Eligibility: Inpatients with lab-confirmed Ebola Disease.
• Treatment Arms (Factorial Design - Subject to availability & patient suitability):
  • Virus-directed Therapy (SUDV infection only): Remdesivir vs. MBP134 (Monoclonal Antibody) vs. Remdesivir+MBP134 (1:1:1).
  • Host-directed Therapy (All eligible patients): Low-dose Corticosteroids vs. No additional treatment (1:1).
• Standard of Care: All patients receive WHO-recommended supportive care. Licensed therapies, if available, may be administered appropriately.
• Outcomes:
  • Primary: Mortality at 28 days post-randomization.
  • Secondary: Time to viral clearance (first negative PCR test).

Safety Considerations

• Focus on Suspected Serious Adverse Reactions (SSARs) and Suspected Unexpected Serious Adverse Reactions (SUSARs).
• Limited recording of non-serious or non-related events due to the severity of the disease.
• Interim analyses monitored by an independent Data Monitoring Committee (DMC) for potential early stopping based on efficacy/futility. Study team/staff/patients remain blinded (except DMC/PI) until potential outcome decisions.
• Specific concerns raised for Remdesivir (infusion/blood reaction risk - pending confirmation) and MBP134 (potential infusion reaction risk).

Organisation

• Sponsors: WHO, Uganda Ministry of Health.
• Coordinators: Central Coordinating Office (CCO).
• Principal Investigators: Dr. Paska Apiyo (Gulu, Uganda), Prof. Pauline Byakika-Kibwika (Makerere University, Uganda). Site Principal Investigators planned for other countries/outbreaks.

Summary

The protocol details an adaptive, landmark platform trial designed to rapidly generate robust evidence on the best available therapies for the current SUDV outbreak in Uganda and future Ebola outbreaks globally. It uses a streamlined approach to accommodate Uganda's resource setting and follow a factorial design to test a combination of antiviral (Remdesivir, MBP134) and potential host-directed therapies (Corticosteroids). The study emphasizes monitoring patient safety and aims to inform clinical practice for Ebola patients until clear trial outcomes are achieved.