Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT31-1 for Treating ARDS
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-65
SponsorHTIC, Inc
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Sequential
Treatments tested in this trial
HT31-1
DrugHT-1 is a humanized monoclonal antibody developed by HTIC, Inc as a treatment for Acute Respiratory Distress Syndrome (ARDS) Due to an Infectious Source
Saline (0.9%, sterile, for infusion)
Other interventionSaline is as placebo control
Treatment groups
24 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Cohort 1: 1 mg/kgExperimental treatment 1 intervention
Group B: Cohort 1: PlaceboPlacebo comparator 1 intervention
Group C: Cohort 2: 5 mg/kgExperimental treatment 1 intervention
Group D: Cohort 2: PlaceboPlacebo comparator 1 intervention
Group E: Cohort 3: 20 mg/kgExperimental treatment 1 intervention
Group F: Cohort 3: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
0-28 days2
Assess dose-limiting toxicities (DLTs)
Number and percentage of participants experiencing DLTs at each dose level.
Time frame
0-28 daysSecondary outcomes
1
Maximum observed concentration (Cmax)
Maximum observed plasma concentration (Cmax) of HT31-1 following single intravenous administration.
Time frame
From pre-dose through Day 28 post-dose2
Time to maximum concentration (Tmax)
Time to reach the maximum observed plasma concentration (Tmax) of HT31-1 following single intravenous administration.
Time frame
From pre-dose through Day 28 post-dose3
Area under the curve (AUC)
Area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t )and from time zero extrapolated to infinity (AUC0-∞) of HT31-1 following single intravenous administration.
Time frame
From pre-dose through Day 28 post-dose4
Half-life (t1/2)
Time for serum concentration to decrease by half in the terminal phase.
Time frame
From pre-dose through Day 28 post-doseOther outcomes
1
Incidence of Anti-Drug Antibodies (ADA)
Incidence of treatment-emergent anti-drug antibodies (ADA) against HT31-1.
Time frame
From pre-dose through Day 28 post-dose2
Titer of Anti-Drug Antibodies (ADA)
Titer of treatment-emergent anti-drug antibodies (ADA) against HT31-1.
Time frame
From pre-dose through Day 28 post-dose Source ClinicalTrials.gov