This is a Phase 1a/1b, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of TER-1754 (a novel AKT1 inhibitor) in patients with HHT.
This is a first-in-human, Phase 1, multicenter trial that includes two parts: * Phase 1a (dose escalation) will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of TER-1754 in patients with HHT and determine the maximum tolerated or administered dose. * Phase 1b (proof of concept) will evaluate clinical activity and further characterize the safety profile of TER-1754 in patients with HHT. The Phase 1b treatment period is separated into a blinded treatment segment followed by an open-label extension (OLE) segment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
Innovative Hematology, Inc.
Indianapolis, Indiana, United States
RECRUITINGPhase 1a: Safety and Tolerability of TER-1754
Incidence of adverse events characterized by type, seriousness, relationship to study treatment, and severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time frame: up to 48 weeks
Phase 1a: Maximum Tolerated Dose (MTD) and/or Maximum Administrated Dose (MAD) of TER-1754
Incidence dose-limiting toxicities (DLTs) characterized by type, seriousness, and severity according to NCI CTCAE v5.0 (dose escalation only).
Time frame: 28 days
Phase 1b - Evaluate the Change from baseline in epistaxis and symptom-related clinical activity scores at Week 24
Assess change from baseline in epistaxis duration
Time frame: 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Peak Plasma Concentration (Cmax)
Cmax of TER-1754 following single and multiple dosing.
Time frame: up to 48 weeks
Phase 1a and 1b: Evaluate change from baseline in Daily Epistaxis (EQ) Questionnaire
Change from baseline in EQ Questionnaire based on patient self-reported epistaxis frequency, severity and duration, where: Epistaxis frequency: number of epistaxis events per week Epistaxis duration: total minutes of bleeding Epistaxis intensity - From mild to severe: Spotting, dripping, dripping quickly, steady stream, pouring, and gushing.
Time frame: up to 48 weeks
Phase 1a and 1b: Evaluate HHT-specfic quality of life
Change from baseline in HHT-specific QoL (HHT-QoL), where The total score ranges from 0 (no limitations) to 16 (severe limitations).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Time to Peak Concentration (Tmax)
Time at which maximum observed plasma concentration occurs.
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Area Under the Concentration-Time Curve (AUC0-last)
Area under the plasma concentration-time curve from time zero to last measurable concentration (AUC0-last)
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 AUC0-24
Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24)
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 AUC∞
Area under the plasma concentration versus time curve extrapolated to infinity (AUC∞) of TER-1754 following single and multiple dosing.
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Terminal Half-Life (t½)
Terminal elimination half-life (t½) of TER-1754 calculated from the terminal slope of the plasma concentration versus time profile.
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Mean Residence Time (MRT)
Mean residence time (MRT) of TER-1754.
Time frame: Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Accumulation Ratio at Steady State
Accumulation ratio of TER-1754 at steady state, calculated as the ratio of exposure at steady state to exposure after the first dose.
Time frame: Up to 48 weeks
Phase 1a and 1b: Change from baseline in Nasal Obstruction Symptom Evaluation Score for HHT (NOSE HHT)
Change from baseline in the NOSE HHT score, a validated scale measuring nasal obstruction in HHT. The score ranges from 0 to 4, with higher scores indicating more severe symptoms.
Time frame: up to 48 weeks