DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia (DIAMOND)

A Phase 1/2, First-in-Human, Multicenter, Ascending Single-Dose and Multi-Dose Study to Assess the Safety of DIAG723, a Novel Bispecific ALK-1 and BMPRII Agonist Antibody in Adult Patients With Hereditary Hemorrhagic Telangiectasia (DIAMOND Trial)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pulmonary Arterial Hypertension; Hereditary Hemorrhagic Telangiectasia
• Intervention / Treatment: Biological: DIAG723; Other: Placebo

Detailed Description

This is a Phase 1/2, randomized, double-blind, placebo-controlled, first-in-human, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of DIAG723, a bispecific agonist monoclonal antibody targeting activin receptor-like kinase 1 (ALK-1) and bone morphogenetic protein receptor type II (BMPRII), in adult patients with hereditary hemorrhagic telangiectasia (HHT).

The study is conducted in three sequential parts (Parts A, B, and C), each evaluating different dosing strategies and patient populations.

Part A (Single Ascending DoseDose in HHT):

Part A is a dose-escalation phase evaluating ascending single-dose levels of DIAG723 administered subcutaneously in sequential cohorts. Within each cohort, participants are randomized to receive DIAG723 or placebo. Dose escalation proceeds in a stepwise manner following review of safety, tolerability, and pharmacokinetic data. Sentinel dosing is implemented to allow for early safety assessment prior to dosing additional participants. Participants are monitored in an inpatient setting following dosing, with continued outpatient follow-up through the end of the assessment period.

Part B (Multiple-Dose Expansion in HHT):

Part B evaluates the safety, tolerability, pharmacokinetics, and preliminary clinical activity of DIAG723 administered as a multiple-dose regimen in patients with HHT symptoms. Participants are randomized to receive DIAG723 or placebo and receive repeated subcutaneous administrations over a planned treatment period of approximately 13 weeks. Dose levels and regimens evaluated in Part B are informed by available safety, pharmacokinetic, and pharmacodynamic data from Part A. An independent data monitoring process is used to support dose selection and cohort progression.

Part C (Multiple-Dose Expansion in HHT with Pulmonary Arterial Hypertension):

Part C evaluates the safety, tolerability, pharmacokinetics, and clinical effects of DIAG723 in a population of patients with HHT and concomitant pulmonary arterial hypertension. Participants are randomized to receive DIAG723 or placebo and receive the same general multiple-dose treatment approach as in Part B. Dose selection for Part C is informed by cumulative data from Part A and Part B, with additional assessments conducted to characterize effects in this specific patient population.

Across all study parts, participants are randomized using an interactive response system, and study treatment is administered under double-blind conditions. A Safety Review Committee and an independent Data Safety Monitoring Board provide ongoing review of safety data and support dose-escalation and progression decisions throughout the study. Dose escalation and cohort progression are guided by predefined safety criteria and overall risk-benefit assessment.

All doses are administered by subcutaneous injection, and participants undergo safety monitoring, pharmacokinetic sampling, and clinical assessments at scheduled study visits. The study includes both inpatient and outpatient components depending on the study part and stage of participation.

This study is designed to characterize the safety profile and pharmacokinetic properties of DIAG723 and to support selection of appropriate doses and regimens for further clinical development in HHT.

• Study Type: Interventional
• Enrollment (Estimated): 93
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Diagonal Therapeutics; Phone Number: 339-233-4291; Email: clinicalinfo@diagonaltx.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
      • Principal Investigator: Edmund Lau, MD
      • Contact: Phone Number: +61 (02) 9382 5800; Email: contactus@scientiaclinicalresearch.com.au
    • Randwick, New South Wales, Australia, 2031
      • Scientia Clinical Research Ltd
      • Principal Investigator: Christopher Argent, MD
      • Contact: Phone Number: +61 (02) 9382 5800; Email: contactus@scientiaclinicalresearch.com.au
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Doherty Clinical Trials
      • Principal Investigator: James McCarthy, MD
      • Contact: Phone Number: (03) 9970 4200; Email: info@dohertyclinicaltrials.com
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • New Zealand Clinical Research - Auckland
      • Contact: Emily Randell; Phone Number: 7153 +64 9 373 3474; Email: dream.auckland@nzcr.co.nz
      • Principal Investigator: Rohit Katial, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DIAG723; 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; 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
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; Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part A	Plasma AUC following single-dose administration of DIAG723.	Pre-dose through Day 28
Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part A	Maximum observed plasma concentration following single-dose administration.	Pre-dose through Day 28
Time to Maximum Plasma Concentration (Tmax) of DIAG723 - Part A	Time to reach maximum plasma concentration following single-dose administration.	Pre-dose through Day 28
Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part B (Multiple Dose)	Plasma AUC following repeated dosing of DIAG723.	Pre-dose through 28 days after final dose
Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part B (Multiple Dose)	Maximum observed plasma concentration following multiple-dose administration.	Pre-dose through 28 days after final dose
Time to Maximum Plasma Concentration (Tmax) of DIAG723 - Part B (Multiple Dose)	Time to reach maximum plasma concentration following multiple-dose administration.	Pre-dose through 28 days after final dose
Incidence of Anti-Drug Antibodies (ADA) to DIAG723 - Part A (Single Dose)	Number and proportion of participants with detectable anti-drug antibodies following single-dose administration.	From first dose through Day 28
Incidence of Anti-Drug Antibodies (ADA) to DIAG723 - Part B (Multiple Dose)	Number and proportion of participants with detectable anti-drug antibodies following multiple-dose administration.	From first dose through 28 days after final dose
Change from Baseline in Epistaxis Frequency - Part B (Multiple Dose)	Change from baseline in frequency of epistaxis events as recorded in a participant-reported electronic daily diary.	Baseline through end of treatment (13 weeks)
Change from Baseline in Epistaxis Flow Intensity, Duration, and Intensity-Adjusted Duration - Part B (Multiple Dose)	Change from baseline in epistaxis flow intensity, event duration, and intensity-adjusted duration as recorded in an electronic daily diary.	Baseline through end of treatment (13 weeks)
Change from Baseline in Hemoglobin - Part B (Multiple Dose)	Change from baseline in hemoglobin concentration.	Baseline through Week 15
Change from Baseline in Hematocrit - Part B (Multiple Dose)	Change from baseline in hematocrit.	Baseline through Week 15
Change in Mean Corpuscular Volume (MCV) Following Multi-dose Treatment With DIAG723 (Part B)	Change from baseline in mean corpuscular volume (MCV, fL) during Part B following multi-dose treatment with DIAG723.	Baseline through Week 15
Change from Baseline in Red Blood Cell Count Following Multi-dose Treatment With DIAG723		Baseline through Week 15
Change from Baseline in White Blood Cell Count Following Multi-dose Treatment With DIAG723 (Part B)		Baseline through Week 15
Change from Baseline in Platelet Count Following Multi-dose Treatment With DIAG723 (Part B)		Baseline through Week 15
Change in Red Blood Cell (RBC) Units Transfused During Treatment With DIAG723 (Part B)	Change from baseline in the number of RBC units transfused, comparing a pre-treatment baseline period to the on-treatment period during Part B.	Baseline through Week 15
Change in Elemental Iron Infused During Treatment With DIAG723 (Part B)	Change from baseline in total milligrams of elemental iron administered via infusion, comparing a pre-treatment baseline period to the on-treatment period during Part B.	Baseline through Week 15
Change in Hematologic Support Score (HSS) Following Treatment With DIAG723 (Part B)	The Hematologic Support Score ranges from 0 to 100, with higher scores indicating greater transfusion and iron supplementation burden and worse outcomes.	Baseline through Week 17
Change in Hematologic Impact Score (HIS) Following Treatment With DIAG723 (Part B)	The Hematologic Impact Score ranges from 0 to 100, with higher scores indicating greater hematologic disease burden and worse outcomes.	Baseline through Week 17

Collaborators and Investigators

• Sponsor: Diagonal Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 2, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: HHT; Hereditary Hemorrhagic Telangiectasia; BMPRII; ALK1; Bone morphogenetic protein receptor type II
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Vascular Malformations; Hypertension, Pulmonary; Telangiectasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Pulmonary Arterial Hypertension; Telangiectasia, Hereditary Hemorrhagic
• Other Study ID Numbers: DIAG723-PT-CL-001

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