A Trial of TER-1754 in Patients With Hereditary Hemorrhagic Telangiectasia

A Phase 1 Trial of TER-1754 in Patients With Hereditary Hemorrhagic Telangiectasia

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.

Study Overview

• Status: Withdrawn
• Conditions: Hereditary Hemorrhagic Telangiectasia (HHT)
• Intervention / Treatment: Drug: TER-1754; Drug: TER-1754; Drug: Placebo

Detailed Description

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
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Innovative Hematology, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
• A clinical diagnosis of HHT as defined by the Curaçao criteria
• Baseline (1-month) ESS ≥ 4
• ECOG ≤ 2
• Anemia or parental iron infusion of at least 500 mg or transfusion of at least 2 units of RBCs within the preceding 24 weeks.
• Adequate bone marrow function
• Adequate renal function
• Adequate hepatic function

Exclusion Criteria:

• Prior nonresponse or loss of response to an agent that inhibits AKT1 and/or AKT2 as the primary mechanism of action.
• Diagnosis of DM requiring insulin treatment
• Known significant bleeding sources other than nasal, GI, or menstrual/ uterine
• Known underlying hypoproliferative anemia or clinically significant hemolytic anemia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a (Dose Escalation) TER-1754 dose escalation; TER-1754 Oral tablets	Drug: TER-1754; QD or BID, orally in 28-day cycles; Drug: TER-1754; Phase 1b dose to be determined post Phase 1a
Placebo Comparator: Phase 1b (Proof of Concept); Placebo oral tablets	Drug: Placebo; Number of tablets will be confirmed post Phase 1a
Experimental: Phase 1b (Proof of Concept) - Phase 1b TER-1754 lower dose to begin post determination in Phase 1a; Patient will receive one of the two doses determined post Phase 1a	Drug: TER-1754; QD or BID, orally in 28-day cycles; Drug: TER-1754; Phase 1b dose to be determined post Phase 1a
Experimental: Phase 1b (Proof of Concept) - Phase 1b TER-1754 higher dose to begin post determination in Phase 1a.; Patient will receive one of the two doses determined post Phase 1a	Drug: TER-1754; QD or BID, orally in 28-day cycles; Drug: TER-1754; Phase 1b dose to be determined post Phase 1a

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 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	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).	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	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1a and 1b: Evaluate TER-1754 Peak Plasma Concentration (Cmax)	Cmax of TER-1754 following single and multiple dosing.	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.	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).	Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Time to Peak Concentration (Tmax)	Time at which maximum observed plasma concentration occurs.	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)	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)	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.	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.	Up to 48 weeks
Phase 1a and 1b: Evaluate TER-1754 Mean Residence Time (MRT)	Mean residence time (MRT) of TER-1754.	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.	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.	up to 48 weeks

Collaborators and Investigators

• Sponsor: Terremoto Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 20, 2025
• First Posted (Actual): December 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; HHT; Arteriovenous Malformation; AVM; Epistaxis; Hereditary hemorrhagic telangiectasia; Nosebleed; Osler-Weber-Rendu; ENG, ACVRL1/ALK-1 alterations
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Respiratory Tract Diseases; Hemorrhage; Hematologic Diseases; Congenital Abnormalities; Nose Diseases; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Vascular Malformations; Telangiectasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Epistaxis; Anemia; Telangiectasia, Hereditary Hemorrhagic; Arteriovenous Malformations
• Other Study ID Numbers: TER-1754-C01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No