Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT31-1 for Treating ARDS

Summary

This Phase 1/2A, randomized, double-blind study will evaluate the safety, tolerability, and pharmacokinetics (PK) of HT31-1 (hCitH3-mAb) in healthy adult volunteers and in patients with mild-to-moderate acute respiratory distress syndrome (ARDS) due to an infectious source. The current trial (Part A) focuses on single ascending doses (SAD) in healthy volunteers to characterize the safety profile, PK parameters, and immunogenicity of HT31-1. Emerging data from this phase will inform dose selection for the subsequent Part B study in ARDS patients and help establish the recommended Phase 2 dose (RP2D). Additionally, exploratory pharmacodynamic and biomarker assessments will be performed to evaluate target engagement and potential early biological activity.

Timeline

Start

2026-05

Primary completion

2026-11

Completion

2026-11

Publications

• Background Weber M, Chen Y, Zhou X, Chun H, Wu D, Park KH, Cai C, Li Y, Ma J, Yang Z. Humanized Monoclonal Antibody Against Citrullinated Histone H3 Attenuates Myocardial Injury and Prevents Heart Failure in Rodent Models. Biomolecules. 2025 Aug 20;15(8):1196. doi: 10.3390/biom15081196.
• Background Ouyang W, Chen Y, Tan T, Song Y, Dong T, Yu X, Lee KE, Zhou X, Tetz Z, Go S, Zeng X, Shao L, Quan C, Zhao T, Tian Y, Kurabayashi K, Jin H, Ma J, Qin J, Williams B, Li Q, Zhu GD, Alam HB, Stringer KA, Li Y, Ma J. A citrullinated histone H3 monoclonal antibody for immune modulation in sepsis. Nat Commun. 2025 Aug 12;16(1):7435. doi: 10.1038/s41467-025-62788-6.
• Background Aziz DZ, Binion CC, Xu H, Wang X, Rodgers S, Gillis DC, Ledford BT, Siletzky R, Zhou X, Li Y, Cai C, Tsihlis ND, Ma J, Kibbe MR. Humanized Citrullinated Histone H3 Monoclonal Antibody Improves Respiratory Function and Attenuates Neutrophil-Mediated Inflammation in a Rodent Model of Smoke Inhalation Lung Injury. J Am Coll Surg. 2026 Jan 1;242(1):1-12. doi: 10.1097/XCS.0000000000001620. Epub 2025 Dec 17.

Drugs

Indications