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DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia (DIAMOND)

28. května 2026 aktualizováno: 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Odhadovaný)

93

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní místa

  • Austrálie
    • New South Wales
      • Camperdown, New South Wales, Austrálie, 2050
      • Randwick, New South Wales, Austrálie, 2031
    • Victoria
      • East Melbourne, Victoria, Austrálie, 3002
        • Doherty Clinical Trials
        • Vrchní vyšetřovatel:
          • James McCarthy, MD
        • Kontakt:
      • Parkville, Victoria, Austrálie, 3050
        • Royal Melbourne Hospital
  • Nový Zéland
    • Auckland
      • Grafton, Auckland, Nový Zéland, 1010
        • New Zealand Clinical Research - Auckland
        • Kontakt:
        • Vrchní vyšetřovatel:
          • Rohit Katial, MD

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

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

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Trojnásobný

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Biologický: 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
Komparátor placeba: 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).
Jiný: Placebo
Sterile normal saline (0.9% NaCl) administered subcutaneously in volumes matched to DIAG723 to maintain study blinding.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Incidence of Treatment-Emergent Adverse Events (TEAEs) - Part A (Single Dose)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: Baseline through Week 17
Change from baseline in ECG parameters, including QTc interval.
Baseline through Week 17

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Area Under the Plasma Concentration-Time Curve (AUC) of DIAG723 - Part A
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: Baseline through Week 15
Change from baseline in hemoglobin concentration.
Baseline through Week 15
Change from Baseline in Hematocrit - Part B (Multiple Dose)
Časové okno: 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)
Časové okno: 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
Časové okno: Baseline through Week 15
Baseline through Week 15
Change from Baseline in White Blood Cell Count Following Multi-dose Treatment With DIAG723 (Part B)
Časové okno: Baseline through Week 15
Baseline through Week 15
Change from Baseline in Platelet Count Following Multi-dose Treatment With DIAG723 (Part B)
Časové okno: Baseline through Week 15
Baseline through Week 15
Change in Red Blood Cell (RBC) Units Transfused During Treatment With DIAG723 (Part B)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Diagonal Therapeutics, Inc.

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

2. června 2026

Primární dokončení (Odhadovaný)

30. listopadu 2027

Dokončení studie (Odhadovaný)

31. prosince 2027

Termíny zápisu do studia

První předloženo

19. května 2026

První předloženo, které splnilo kritéria kontroly kvality

28. května 2026

První zveřejněno (Aktuální)

3. června 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

3. června 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

28. května 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • DIAG723-PT-CL-001

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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