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DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia (DIAMOND)

2 de septiembre de 2026 actualizado por: Diagonal Therapeutics, Inc.

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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

93

Fase

  • Fase 2
  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Aún no reclutando
        • Diagonal Investigational Site
      • Randwick, New South Wales, Australia, 2031
        • Reclutamiento
        • Diagonal Investigational Site
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Aún no reclutando
        • Diagonal Investigational Site
      • Herston, Queensland, Australia, 4029
        • Retirado
        • Diagonal Investigational Site
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Reclutamiento
        • Diagonal Investigational Site
      • Parkville, Victoria, Australia, 3052
        • Aún no reclutando
        • Diagonal Investigational Site
    • Western Australia
      • West Perth, Western Australia, Australia, 6005
        • Aún no reclutando
        • Diagonal Investigational Site
  • Canadá
    • Ontario
      • Toronto, Ontario, Canadá, M5B1W8
        • Aún no reclutando
        • Diagonal Investigational Site
      • Toronto, Ontario, Canadá, M9L 3A2
        • Aún no reclutando
        • Diagonal Investigational Site
    • Quebec
      • Laval, Quebec, Canadá, H7V 4B3
        • Aún no reclutando
        • Diagonal Investigational Site
  • Nueva Zelanda
    • Auckland
      • Grafton, Auckland, Nueva Zelanda, 1010
        • Reclutamiento
        • Diagonal Investigational Site

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Triple

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Biológico: 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
Comparador de placebos: 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).
Otro: Placebo
Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part A (Single Dose)
Periodo de tiempo: From first dose through Day 28
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)
Periodo de tiempo: From first dose through Day 28
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)
Periodo de tiempo: From first dose through Day 28
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)
Periodo de tiempo: 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.
Baseline through Day 28
Number of participants with abnormal vital signs - Part A (Single Dose)
Periodo de tiempo: Baseline through Day 28
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)
Periodo de tiempo: Baseline through Day 28
Change from baseline in ECG parameters, including QTc interval.
Baseline through Day 28
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part B (Multiple Dose)
Periodo de tiempo: From first dose through 28 days after final 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)
Periodo de tiempo: From first dose through 28 days after final 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)
Periodo de tiempo: From first dose through 28 days after final 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)
Periodo de tiempo: 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.
Baseline through Week 15
Number of participants with abnormal vital signs - Part B (Multiple Dose)
Periodo de tiempo: Baseline through Week 17
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)
Periodo de tiempo: Baseline through Week 17
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)
Periodo de tiempo: 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.
From first dose through 28 days after final dose
Incidence of Serious Adverse Events (SAEs) - Part C (Multiple Dose, HHT with PAH)
Periodo de tiempo: From first dose through 28 days after final dose
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)
Periodo de tiempo: From first dose through 28 days after final dose
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)
Periodo de tiempo: 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.
Baseline through Week 15
Number of participants with abnormal vital signs - Part C (Multiple Dose, HHT with PAH)
Periodo de tiempo: Baseline through Week 17
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)
Periodo de tiempo: Baseline through Week 17
Change from baseline in ECG parameters, including QTc interval.
Baseline through Week 17

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part A
Periodo de tiempo: Pre-dose through Day 28
Plasma AUC following single-dose administration of DIAG723.
Pre-dose through Day 28
Maximum Observed Plasma Concentration (Cmax) of DIAG723 - Part A
Periodo de tiempo: Pre-dose through Day 28
Maximum observed plasma concentration following single-dose administration.
Pre-dose through Day 28
Time to Maximum Plasma Concentration (Tmax) of DIAG723 - Part A
Periodo de tiempo: Pre-dose through Day 28
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)
Periodo de tiempo: Pre-dose through 28 days after final 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)
Periodo de tiempo: Pre-dose through 28 days after final 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)
Periodo de tiempo: Pre-dose through 28 days after final 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)
Periodo de tiempo: From first dose through Day 28
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)
Periodo de tiempo: From first dose through 28 days after final 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)
Periodo de tiempo: Baseline through end of treatment (13 weeks)
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)
Periodo de tiempo: Baseline through end of treatment (13 weeks)
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)
Periodo de tiempo: Baseline through Week 15
Change from baseline in hemoglobin concentration.
Baseline through Week 15
Change from Baseline in Hematocrit - Part B (Multiple Dose)
Periodo de tiempo: Baseline through Week 15
Change from baseline in hematocrit.
Baseline through Week 15
Change in Mean Corpuscular Volume (MCV) Following Multi-dose Treatment With DIAG723 (Part B)
Periodo de tiempo: Baseline through Week 15
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
Periodo de tiempo: Baseline through Week 15
Baseline through Week 15
Change from Baseline in White Blood Cell Count Following Multi-dose Treatment With DIAG723 (Part B)
Periodo de tiempo: Baseline through Week 15
Baseline through Week 15
Change from Baseline in Platelet Count Following Multi-dose Treatment With DIAG723 (Part B)
Periodo de tiempo: Baseline through Week 15
Baseline through Week 15
Change in Red Blood Cell (RBC) Units Transfused During Treatment With DIAG723 (Part B)
Periodo de tiempo: Baseline through Week 15
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)
Periodo de tiempo: Baseline through Week 15
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)
Periodo de tiempo: Baseline through Week 17
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)
Periodo de tiempo: Baseline through Week 17
The Hematologic Impact Score ranges from 0 to 100, with higher scores indicating greater hematologic disease burden and worse outcomes.
Baseline through Week 17

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Diagonal Therapeutics, Inc.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

4 de junio de 2026

Finalización primaria (Estimado)

30 de noviembre de 2027

Finalización del estudio (Estimado)

31 de diciembre de 2027

Fechas de registro del estudio

Enviado por primera vez

19 de mayo de 2026

Primero enviado que cumplió con los criterios de control de calidad

28 de mayo de 2026

Publicado por primera vez (Actual)

3 de junio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de septiembre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

2 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • DIAG723-PT-CL-001

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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