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

NCT07255846 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: TER-1754-C01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hereditary Hemorrhagic Telangiectasia (HHT)

Keywords

Hereditary hemorrhagic telangiectasia; ENG, ACVRL1/ALK-1 alterations; Osler-Weber-Rendu; HHT; Anemia; Nosebleed; Epistaxis; AVM; Arteriovenous Malformation

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Phase 1a and 1b: Evaluate TER-1754 Peak Plasma Concentration (Cmax)

  up to 48 weeks

• Phase 1a and 1b: Evaluate change from baseline in Daily Epistaxis (EQ) Questionnaire

  up to 48 weeks

• Phase 1a and 1b: Evaluate HHT-specfic quality of life

  Up to 48 weeks

• Phase 1a and 1b: Evaluate TER-1754 Time to Peak Concentration (Tmax)

  Up to 48 weeks

• Phase 1a and 1b: Evaluate TER-1754 Area Under the Concentration-Time Curve (AUC0-last)

  Up to 48 weeks

Study Arms (4)

Phase 1a (Dose Escalation) TER-1754 dose escalation

EXPERIMENTAL

TER-1754 Oral tablets

Drug: TER-1754

Phase 1b (Proof of Concept)

PLACEBO COMPARATOR

Placebo oral tablets

Drug: Placebo

Phase 1b (Proof of Concept) - Phase 1b TER-1754 lower dose to begin post determination in Phase 1a

EXPERIMENTAL

Patient will receive one of the two doses determined post Phase 1a

Drug: TER-1754

Phase 1b (Proof of Concept) - Phase 1b TER-1754 higher dose to begin post determination in Phase 1a.

EXPERIMENTAL

Patient will receive one of the two doses determined post Phase 1a

Drug: TER-1754

Interventions

Placebo DRUG

Number of tablets will be confirmed post Phase 1a

Phase 1b (Proof of Concept)

TER-1754 DRUG

QD or BID, orally in 28-day cycles

Phase 1a (Dose Escalation) TER-1754 dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Terremoto Biosciences Inc.: lead

Study Sites (1)

Innovative Hematology, Inc.

Indianapolis, Indiana, 46260, United States

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Anemia; Epistaxis; Arteriovenous Malformations

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Phase 1a is open label, dose escalation. The Phase 1b treatment period is separated into a blinded treatment segment followed by an open-label extension (OLE) segment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1a is an open-label dose-escalation trial. Phase 1b is a 3-arm randomized placebo-controlled design. The Phase 1b treatment period is separated into a blinded treatment segment followed by an open-label extension (OLE) segment

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 1, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)