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: Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part A (Single Dose) — From first dose through Day 28 Number and proportion of participants experiencing TEAEs following single-dose administration of DIAG723.
Incidence of Serious Adverse Events (SAEs) - Part A (Single Dose) — From first dose through Day 28 Number and proportion of participants experiencing SAEs following single-dose administration of DIAG723.
Incidence of Dose-Limiting Toxicities (DLTs) - Part A (Single Dose) — From first dose through Day 28 Number and proportion of participants experiencing DLTs during the dose-escalation period following single-dose administration.
Number of participants with abnormal laboratory tests results - Part A (Single Dose) — Baseline through Day 28 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.
Number of participants with abnormal vital signs - Part A (Single Dose) — Baseline through Day 28 Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.
Change from Baseline in Electrocardiogram (ECG) Parameters - Part A (Single Dose) — Baseline through Day 28 Change from baseline in ECG parameters, including QTc interval.
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part B (Multiple Dose) — From first dose through 28 days after final dose Number and proportion of participants experiencing TEAEs following multiple-dose administration of DIAG723.
Incidence of Serious Adverse Events (SAEs) - Part B (Multiple Dose) — From first dose through 28 days after final dose Number and proportion of participants experiencing SAEs following multiple-dose administration.
Incidence of Dose-Limiting Toxicities (DLTs) - Part B (Multiple Dose) — From first dose through 28 days after final dose Number and proportion of participants experiencing DLTs during multiple-dose treatment.
Number of participants with abnormal laboratory tests results - Part B (Multiple Dose) — Baseline through Week 15 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.
Number of participants with abnormal vital signs - Part B (Multiple Dose) — Baseline through Week 17 Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.
Change from Baseline in Electrocardiogram (ECG) Parameters - Part B (Multiple Dose) — Baseline through Week 17 Change from baseline in ECG parameters, including QTc interval.
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part C (Multiple Dose, HHT with PAH) — From first dose through 28 days after final dose Number and proportion of participants experiencing TEAEs following multiple-dose administration in participants with HHT and pulmonary arterial hypertension.
Incidence of Serious Adverse Events (SAEs) - Part C (Multiple Dose, HHT with PAH) — From first dose through 28 days after final dose Number and proportion of participants experiencing SAEs in this population.
Incidence of Dose-Limiting Toxicities (DLTs) - Part C (Multiple Dose, HHT with PAH) — From first dose through 28 days after final dose Number and proportion of participants experiencing DLTs during treatment.
Number of participants with abnormal laboratory tests results - Part C (Multiple Dose, HHT with PAH) — Baseline through Week 15 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.
Number of participants with abnormal vital signs - Part C (Multiple Dose, HHT with PAH) — Baseline through Week 17 Vital sign measurements include body temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation.
Change from Baseline in Electrocardiogram (ECG) Parameters - Part C (Multiple Dose, HHT with PAH) — Baseline through Week 17 Change from baseline in ECG parameters, including QTc interval.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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