A Phase 1/2 interventional study of DIAG723 and Placebo in Hereditary Hemorrhagic Telangiectasia and Pulmonary Arterial Hypertension, sponsored by Diagonal Therapeutics, Inc.. Recruiting at 11 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.
Sponsored by Diagonal Therapeutics, Inc. · Phase 1/2, Interventional, and Treatment
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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.
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.
106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.
This study's planned enrollment of 93 is above the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.
Browse Telangiectasia, Hereditary Hemorrhagic studies →This is the only study on the registry with Diagonal Therapeutics, Inc. as lead sponsor.
Counted across the registry records on this site, refreshed daily.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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
Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part A (Single Dose)
Number and proportion of participants experiencing TEAEs following single-dose administration of DIAG723.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through Day 28
Change from Baseline in Electrocardiogram (ECG) Parameters - Part A (Single Dose)
Change from baseline in ECG parameters, including QTc interval.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through Week 17
Change from Baseline in Electrocardiogram (ECG) Parameters - Part B (Multiple Dose)
Change from baseline in ECG parameters, including QTc interval.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through Week 17
Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part A
Plasma AUC following single-dose administration of DIAG723.
Time frame: Pre-dose through Day 28
Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part A
Maximum observed plasma concentration following single-dose administration.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through end of treatment (13 weeks)
Change from Baseline in Hemoglobin - Part B (Multiple Dose)
Change from baseline in hemoglobin concentration.
Time frame: Baseline through Week 15
Change from Baseline in Hematocrit - Part B (Multiple Dose)
Change from baseline in hematocrit.
Time frame: 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.
Time frame: Baseline through Week 15
Change from Baseline in Red Blood Cell Count Following Multi-dose Treatment With DIAG723
Time frame: Baseline through Week 15
Change from Baseline in White Blood Cell Count Following Multi-dose Treatment With DIAG723 (Part B)
Time frame: Baseline through Week 15
Change from Baseline in Platelet Count Following Multi-dose Treatment With DIAG723 (Part B)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline through Week 17
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Plan to share: No
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Started Jun 2026 (actual). Primary completion is estimated for Nov 2027, 17 months after the start.
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Telangiectasia, Hereditary Hemorrhagic →