A Phase 1b Trial to Evaluate Safety and Effect of SAR443122 on Immune System in Severe COVID-19

Summary

Primary Objective: To evaluate the effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by C-reactive protein (CRP) levels in adult patients hospitalized with severe coronavirus disease 2019 (COVID-19) Secondary Objectives: * To evaluate the time to onset of effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by CRP levels * To evaluate the time to onset of effect of SAR443122 relative to the control arm on oxygenation status * To evaluate the effect of SAR443122 relative to the control arm on oxygenation status * To evaluate the effect of SAR443122 relative to the control arm on total duration of supplemental oxygen requirement * To evaluate the effect of SAR443122 relative to the control arm on length of ventilator support needed * To evaluate the effect of SAR443122 relative to the control arm on laboratory markers of severe COVID-19 * To evaluate the effect of SAR443122 relative to the control arm on mortality * To evaluate the effect of SAR443122 relative to the control arm on need for thrombolytic therapy * To evaluate the effect of SAR443122 relative to the control arm on need for vasopressor treatment * To evaluate the safety of SAR443122 as compared to the control arm up to End of Study * To evaluate the effect of SAR443122 relative to the control arm on total duration without high flow supplemental oxygen requirements

Timeline

Start

2020-07-17

Primary completion

2020-10-23

Completion

2020-10-23

Outcome

Missed primary endpoint

paper Geometric mean ratio (point estimate [90% confidence interval]) of the relative change from baseline in C-reactive protein with eclitasertib vs. placebo on Day 7 was 0.85 (0.49-1.45; p = 0.30). PMID 38419035 ↗

release “Although the Phase 1b study did not meet its primary endpoint, DNL758 ( SAR443122 )” denalitherapeutics.com ↗

Publications

• Clot PF, Farenc C, Suratt BT, Krahnke T, Tardat A, Florian P, Pomponio R, Patel N, Wiekowski M, Lin Y, Terrier B, Staudinger H. Immunomodulatory and clinical effects of receptor-interacting protein kinase 1 (RIPK1) inhibitor eclitasertib (SAR443122) in patients with severe COVID-19: a phase 1b, randomized, double-blinded, placebo-controlled study. Respir Res. 2024 Feb 28;25(1):107. doi: 10.1186/s12931-024-02670-z.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	eclitasertib	Small molecule	300 mg	Oral

Indications