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

NCT07449572 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PROT-CR-CP25101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

ARDS (Acute Respiratory Distress Syndrome)

Keywords

Acute Respiratory Distress Syndrome (ARDS); Single Ascending Dose; Monoclonal Antibody

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  The number and percentage of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) following administration of HT31-1.

  0-28 days

• Assess dose-limiting toxicities (DLTs)

  Number and percentage of participants experiencing DLTs at each dose level.

  0-28 days

Secondary Outcomes (7)

• Maximum observed concentration (Cmax)

  From pre-dose through Day 28 post-dose

• Time to maximum concentration (Tmax)

  From pre-dose through Day 28 post-dose

• Area under the curve (AUC)

  From pre-dose through Day 28 post-dose

• Half-life (t1/2)

  From pre-dose through Day 28 post-dose

• Clearance (CL)

  From pre-dose through Day 28 post-dose

Other Outcomes (2)

• Incidence of Anti-Drug Antibodies (ADA)

  From pre-dose through Day 28 post-dose

• Titer of Anti-Drug Antibodies (ADA)

  From pre-dose through Day 28 post-dose

Study Arms (6)

Cohort 1: 1 mg/kg

EXPERIMENTAL

HT31-1 1mg/kg single intravenous dosing

Drug: HT31-1

Cohort 1: Placebo

PLACEBO COMPARATOR

Saline single intravenous dosing

Other: Saline (0.9%, sterile, for infusion)

Cohort 2: 5 mg/kg

EXPERIMENTAL

HT31-1 5mg/kg single intravenous dosing

Drug: HT31-1

Cohort 2: Placebo

PLACEBO COMPARATOR

Saline single intravenous dosing

Other: Saline (0.9%, sterile, for infusion)

Cohort 3: 20 mg/kg

EXPERIMENTAL

HT31-1 20mg/kg single intravenous dosing

Drug: HT31-1

Cohort 3: Placebo

PLACEBO COMPARATOR

Saline single intravenous dosing

Other: Saline (0.9%, sterile, for infusion)

Interventions

HT31-1 DRUG

HT-1 is a humanized monoclonal antibody developed by HTIC, Inc as a treatment for Acute Respiratory Distress Syndrome (ARDS) Due to an Infectious Source

Also known as: hCitH3-mAb, humanized anti-citrullinated histone H3 monoclonal antibody

Cohort 1: 1 mg/kg; Cohort 2: 5 mg/kg; Cohort 3: 20 mg/kg

Saline (0.9%, sterile, for infusion) OTHER

Saline is as placebo control

Also known as: Placebo control

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all of the following criteria:
• Age 18 to 65 years old, inclusive, at the time of consent.
• Able and willing to provide written informed consent and to comply with all study procedures and requirements.
• Healthy as determined by medical history, physical examination, and baseline investigations. No clinically significant abnormalities on physical exam.
• Body Mass Index (BMI) between 18.0 and 32.0 kg/m², inclusive.
• Vital signs and 12-lead ECG without clinically significant abnormalities, in the investigator's judgment, at screening (e.g., resting blood pressure and heart rate within normal limits).
• Screening clinical laboratory tests (hematology, chemistry, liver and kidney function, etc.) within normal ranges or not clinically significant as judged by the investigator.
• Female volunteers must be of non-childbearing potential (either surgically sterile by tubal ligation, bilateral oophorectomy or hysterectomy at least 6 months prior, or postmenopausal for ≥1 year) OR if of childbearing potential must agree to use 2 approved effective contraceptions from screening through at least 90 days after the last dose. Acceptable methods include hormonal contraception, intrauterine device, or barrier methods with spermicide.
• Male volunteers with partners of childbearing potential must agree to use 2 approved effective contraception (e.g., condom plus spermicide) from screening through 90 days after their dose of study drug.
• Able to communicate well with the investigator and comply with study requirements (e.g., availability for all follow-up visits).

You may not qualify if:

• Participants will be excluded if they meet any of the following criteria:
• History of any severe allergy or hypersensitivity to drugs, or known hypersensitivity to any monoclonal antibody (including prior biologic therapy reactions).
• Known autoimmune disease or immunodeficiency condition, including a positive test for HIV at screening.
• Active or chronic viral hepatitis infection: positive screening test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody.
• History of tetanus infection, or receipt of tetanus toxoid vaccine within 6 months prior to first dose of study drug. (Rationale: CitH3 is associated with NETs, and recent tetanus immunization may confound immune status or antibody responses).
• Receipt of any live attenuated vaccine within 4 weeks prior to first dose, or any inactivated vaccine within 2 weeks prior to first dose. (This is to avoid confounding immune activation or risk to the volunteer's health).
• History of any significant acute or chronic illness that, in the investigator's opinion, could interfere with the trial or pose additional risk in administering the investigational drug. Examples include significant cardiovascular, hepatic, renal, gastrointestinal, hematologic, neurologic, psychiatric, or respiratory conditions that are not well-controlled.
• Recent major surgery (within 3 months prior to screening) or planned elective surgery during the study period. (Minor outpatient procedures are allowed at the investigator's discretion.)
• Difficulty with venous access or an inability to tolerate blood draws, such that required PK sampling would be compromised.
• Positive screening alcohol breath test, or history of excessive alcohol intake (more than \~14 units per week; 1 unit = 360 mL beer, 150 mL wine, or 45 mL of 40% spirit) within 6 months. Any indication of alcoholism or inability to refrain from alcohol during study participation.
• Use of any prescription or over-the-counter medications, herbal remedies, or supplements within 14 days prior to first dose, except hormonal contraceptives or occasional acetaminophen. (Any necessary medications may be reviewed by the investigator for approval if unlikely to interfere with study outcomes).
• Participation in another clinical trial of an investigational drug or device within 4 weeks (or 5 half-lives of that investigational product, whichever is longer) prior to dosing.
• Donation of \>400 mL of blood (or significant blood loss of similar volume) within 3 months prior to screening, or donation of \>200 mL within 1 month prior. (This is to avoid anemia or confounding volume loss).
• Receipt of any blood products or immunoglobulin therapy within 90 days before dosing.
• Chronic use of immunosuppressive medications (systemic corticosteroids, immunomodulators) within 45 days before dosing (inhaled/topical steroids for mild conditions may be permitted).

Sponsors & Collaborators

• HTIC, Inc: lead

Study Sites (2)

Virginia Commonwealth University (VCU Health)

Richmond, Virginia, 23298, United States

NOT YET RECRUITING

Virginia Commonwealth University (VCU Health)

Richmond, Virginia, 23298, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 40867640 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.

  PMID: 40796783 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.

  PMID: 41051091 BACKGROUND

Related Links

• Sponsor website

MeSH Terms

Conditions

Acute Lung Injury; Respiratory Distress Syndrome

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Jianjie Ma, PhD

  HTIC, Inc

  STUDY DIRECTOR

Central Study Contacts

Lacey Harris, MPH, BSN

CONTACT

804-828-0404; Lacey.Harris@vcuhealth.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: March 4, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)