DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia

NCT07623525 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: DIAG723-PT-CL-001
• Study Type: interventional
• Target: 93
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a Phase 1/2, randomized, double-blind, placebo-controlled, first-in-human study evaluating the safety, tolerability, pharmacokinetics, and preliminary efficacy of subcutaneously administered DIAG723 in adult patients with hereditary hemorrhagic telangiectasia (HHT). The study consists of three parts: Part A (dose escalation): Single ascending subcutaneous doses of DIAG723 are evaluated in sequential cohorts to assess safety, tolerability, and pharmacokinetics. Part B (dose expansion): Multiple doses of DIAG723 administered over 13 weeks are evaluated in patients with HHT to assess safety and preliminary efficacy. Part C (dose expansion): Multiple doses of DIAG723 administered over 13 weeks are evaluated in patients with HHT and concomitant pulmonary arterial hypertension to assess safety and exploratory clinical effects in this population. Participants will be randomized within each study part to receive DIAG723 or placebo. The study includes dose escalation in Part A and dose expansion in Parts B and C.

Conditions

Pulmonary Arterial Hypertension; Hereditary Hemorrhagic Telangiectasia

Keywords

Hereditary Hemorrhagic Telangiectasia; HHT; BMPRII; ALK1; Bone morphogenetic protein receptor type II

Outcome Measures

Primary Outcomes (18)

• Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part A (Single Dose)

  Number and proportion of participants experiencing TEAEs following single-dose administration of DIAG723.

  From first dose through Day 28

• Incidence of Serious Adverse Events (SAEs) - Part A (Single Dose)

  Number and proportion of participants experiencing SAEs following single-dose administration of DIAG723.

  From first dose through Day 28

• Incidence of Dose-Limiting Toxicities (DLTs) - Part A (Single Dose)

  Number and proportion of participants experiencing DLTs during the dose-escalation period following single-dose administration.

  From first dose through Day 28

• Number of participants with abnormal laboratory tests results - Part A (Single Dose)

  Laboratory assessments include hematology (complete blood count), clinical chemistry (basic metabolic panel; liver function tests; renal function; electrolytes; thyroid-stimulating hormone, free T4, free T3; cortisol; luteinizing hormone; lipase; amylase), coagulation (prothrombin time/international normalized ratio, activated partial thromboplastin time), and urinalysis.

  Baseline through Day 28

• Number of participants with abnormal vital signs - Part A (Single Dose)

  Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.

  Baseline through Day 28

• Change from Baseline in Electrocardiogram (ECG) Parameters - Part A (Single Dose)

  Change from baseline in ECG parameters, including QTc interval.

  Baseline through Day 28

• Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part B (Multiple Dose)

  Number and proportion of participants experiencing TEAEs following multiple-dose administration of DIAG723.

  From first dose through 28 days after final dose

• Incidence of Serious Adverse Events (SAEs) - Part B (Multiple Dose)

  Number and proportion of participants experiencing SAEs following multiple-dose administration.

  From first dose through 28 days after final dose

• Incidence of Dose-Limiting Toxicities (DLTs) - Part B (Multiple Dose)

  Number and proportion of participants experiencing DLTs during multiple-dose treatment.

  From first dose through 28 days after final dose

• Number of participants with abnormal laboratory tests results - Part B (Multiple Dose)

  Laboratory assessments include hematology (complete blood count), clinical chemistry (basic metabolic panel; liver function tests; renal function; electrolytes; thyroid-stimulating hormone, free T4, free T3; cortisol; luteinizing hormone; lipase; amylase), coagulation (prothrombin time/international normalized ratio, activated partial thromboplastin time), and urinalysis.

  Baseline through Week 15

• Number of participants with abnormal vital signs - Part B (Multiple Dose)

  Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.

  Baseline through Week 17

• Change from Baseline in Electrocardiogram (ECG) Parameters - Part B (Multiple Dose)

  Change from baseline in ECG parameters, including QTc interval.

  Baseline through Week 17

• Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part C (Multiple Dose, HHT with PAH)

  Number and proportion of participants experiencing TEAEs following multiple-dose administration in participants with HHT and pulmonary arterial hypertension.

  From first dose through 28 days after final dose

• Incidence of Serious Adverse Events (SAEs) - Part C (Multiple Dose, HHT with PAH)

  Number and proportion of participants experiencing SAEs in this population.

  From first dose through 28 days after final dose

• Incidence of Dose-Limiting Toxicities (DLTs) - Part C (Multiple Dose, HHT with PAH)

  Number and proportion of participants experiencing DLTs during treatment.

  From first dose through 28 days after final dose

• Number of participants with abnormal laboratory tests results - Part C (Multiple Dose, HHT with PAH)

  Laboratory assessments include hematology (complete blood count), clinical chemistry (basic metabolic panel; liver function tests; renal function; electrolytes; thyroid-stimulating hormone, free T4, free T3; cortisol; luteinizing hormone; lipase; amylase), coagulation (prothrombin time/international normalized ratio, activated partial thromboplastin time), and urinalysis.

  Baseline through Week 15

• Number of participants with abnormal vital signs - Part C (Multiple Dose, HHT with PAH)

  Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.

  Baseline through Week 17

• Change from Baseline in Electrocardiogram (ECG) Parameters - Part C (Multiple Dose, HHT with PAH)

  Change from baseline in ECG parameters, including QTc interval.

  Baseline through Week 17

Secondary Outcomes (20)

• Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part A

  Pre-dose through Day 28

• Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part A

  Pre-dose through Day 28

• Time to Maximum Plasma Concentration (Tmax) of DIAG723 - Part A

  Pre-dose through Day 28

• Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part B (Multiple Dose)

  Pre-dose through 28 days after final dose

• Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part B (Multiple Dose)

  Pre-dose through 28 days after final dose

Study Arms (2)

DIAG723

EXPERIMENTAL

Participants receive DIAG723 administered subcutaneously. Part A (dose-escalation): Single ascending dose across planned cohorts, randomized 3:1 DIAG723:placebo. Part B (multi-dose HHT): Multiple-dose regimens over 13 weeks (7 doses administered every other week), randomized 2:1. Part C (multi-dose HHT + PAH): Same 13-week multi-dose regimen in patients with pulmonary arterial hypertension, randomized 4:1. Doses/regimens in Parts B and C are selected based on Part A safety and PK data.

Biological: DIAG723

Placebo Comparator

PLACEBO COMPARATOR

Participants receive placebo (sterile normal saline, 0.9% NaCl) administered subcutaneously in a volume matched to DIAG723 to maintain blinding. Matching single-dose administration in Part A. Matching multi-dose regimens (every-other-week dosing for 13 weeks) in Parts B and C. Randomization ratios consistent with each study part (3:1, 2:1, 4:1).

Other: Placebo

Interventions

DIAG723 BIOLOGICAL

Bispecific agonist monoclonal antibody targeting ALK-1 and BMPRII, administered subcutaneously as: Single ascending dose in Part A; Multiple doses (7 doses over 13 weeks) in Parts B and C

DIAG723

Placebo OTHER

Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.

Placebo Comparator

Eligibility Criteria

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

You may qualify if:

• Adult patients ≥18 years with a clinical or genetic diagnosis of HHT
• Adequate hepatic and renal function
• Part B: Epistaxis and anemia or transfusion/iron history
• Part C: HHT with documented pre-capillary pulmonary arterial hypertension

You may not qualify if:

• Active or recent systemic infection
• Recent thromboembolic events
• Use of anti-angiogenic drugs within 6 weeks
• Pregnancy or lactation
• Recent participation in another investigational study

Sponsors & Collaborators

• Diagonal Therapeutics, Inc.: lead

Study Sites (5)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Scientia Clinical Research Ltd

Randwick, New South Wales, 2031, Australia

Location

Doherty Clinical Trials

East Melbourne, Victoria, 3002, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

New Zealand Clinical Research - Auckland

Grafton, Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Pulmonary Arterial Hypertension

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; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Diagonal Therapeutics

CONTACT

339-233-4291; clinicalinfo@diagonaltx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Sponsor team unblinded during Part A for safety evaluation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 3-part sequential study (Parts A, B, and C) with separate randomization within each part

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: June 3, 2026
• Study Start: June 2, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); NZ (1)