2022-11-14-世界卫生组织-Sudan_Ebolavirus_–_Experts_deliberations. _Candidate_treatments_prioritization_and_trial_design_discussions_11页_352kb

Sudan Ebolavirus Treatment Deliberations Summary

October & November 2022

Background

No definitive treatment exists for Sudan ebolavirus (SUDV) infection. In response to the Uganda outbreak, expert consultations assessed candidate therapeutics, trial designs, and developed a proposed clinical trial protocol.

Candidate Treatment Prioritization Criteria

1. Non-human primate (NHP) efficacy data
2. Human safety and pharmacokinetic data
3. Human clinical efficacy (limited for SUDV)
4. Feasibility (including GMP availability)

Prioritised Treatments Available

1. Remdesivir: Recommended for both monotherapy and combination trials
2. Combination monoclonal antibodies (MAbs): MBP134 (Mappbio) prioritized
3. Low-dose corticosteroids (dexamethasone): Recommended for secondary randomization

Investigational Treatments Evaluated

Table 1: Summary of Recommended/Outstanding Status

Therapeutic	Category	Key Outcomes	Status
MBP134	Monoclonal Antibody	Strong NHP efficacy, available soon	PRIORITIZED (both mono & combo)
Inmazeb/MAb	MAb Cocktail	Limited against SUDV	NOT RECOMMENDED FOR TRIAL
CM-JLD1	MAb Cocktail	Incomplete NHP needed	DELAYED
Molnupiravir	Antiviral	Limited SUDV evidence	MONITOR PROGRESS
FX-06	Host Response	Limited clinical data	MONITOR PROGRESS
Convalescent Plasma	Immune-Based	Valid strategy but not prioritized	CONSIDER LATER

Trial Design Recommendations

4 options evaluated, with design 3 selected as the most feasible while maintaining randomization benefits:

1. SOC + Monoclonal Antibody + Antiviral (3 arms) - Recommended Primary Design
2. SOC + Monoclonal Antibody (2 arms) - Limited information
3. SOC + Antiviral only (1 arm) - Conservation strategy
4. No SOC alone arm (only treatment combinations) - Not selected

Proposed Clinical Trial Protocol

• Three-arm design evaluating:
  • Inmazeb/Maftivimab (antibody)
  • Remdesivir (antiviral)
  • Dexamethasone (host-directed)

Conclusions

1. Focus on antibody treatments shows the most promise
2. Co-primary endpoints recommended for future trials
3. Dexamethasone evaluation as a secondary outcome to be confirmed

Key Next Steps

WHO Actions Pending

• Protocol refinement
• Developer coordination
• National regulatory discussions