A Study Assessing HMB-002 in Participants With Von Willebrand Disease

Официальное название

A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-002 in Participants With Von Willebrand Disease (Velora Pioneer)

Обзор

This is a first-in-human (FIH), Phase 1/2, 3-part open-label, dose escalation, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and efficacy study evaluating HMB-002 in participants with VWD. Part A of the study involves a single ascending dose (SAD) regimen design to establish safety, tolerability, PK, and PD effect. In Part B of the study, the safety and tolerability of repeat dosing will be established prior to cohort expansion to explore efficacy. Part C will evaluate the safety, PK, and PD of a single concomitant dose of HMB-002 and factor concentrate with Type 3 VWD or Type 1 VWD with low residual VWF and FVIII who use factor concentrate as prophylaxis.

Вмешательства

• Препарат HMB-002 (Part A)
  HMB-002 will be administered subcutaneously. Part A will utilize sentinel dosing. The planned duration of study participants in Part A is approximately 12 weeks.
• Препарат HMB-002 (Part B)
  HMB-002 will be administered subcutaneously. Part B dosing intervals will be determined following evaluation of Part A results. The planned duration of study participants in Part B will be approximately 21 weeks.
• Препарат HMB-002 with Concomitant Factor Concentrate (Part C) (Not Applicable in US)
  HMB-002 will be administered as a single dose with a concomitant single dose of factor concentrate. The planned duration of study participants in Part C will be approximately 17 weeks.

Первичные конечные точки

• Incidence of Treatment emergent adverse events (TEAE) [Срок оценки: up to Day 113]

Вторичные конечные точки (9)

• Pharmacokinetic Parameter: Maximum observed plasma concentration (Cmax) [Срок оценки: Day 1 to Day 113]
• Pharmacokinetic Parameter: Area under the curve from time zero to last quantifiable concentration (AUClast) [Срок оценки: Day 1 to Day 113]
• Pharmacokinetic Parameter: Area under the curve from time zero to extrapolated infinite time (AUCinf) [Срок оценки: Day 1 to Day 113]
• Pharmacokinetic Parameter: Time to reach maximum observed plasma concentration (Tmax) [Срок оценки: Day 1 to Day 113]
• Pharmacodynamics Parameters: Assessment of VWF antigen (VWF:Ag) [Срок оценки: Day 1 to Day 113]
• Pharmacodynamics Parameters: Assessment of VWF activity [Срок оценки: Day 1 to Day 113]
• Pharmacodynamics Parameters: Assessment of FVIII activity [Срок оценки: Day 1 to Day 113]
• Annualized Bleeding Rate Assessments [Срок оценки: Day 1 to Day 113]
• Pharmacokinetic Parameter: Terminal elimination half-life (t1/2) [Срок оценки: Day 1 to Day 113]

Критерии участия

Критерии включения

• Weight 50 to 120 kg, inclusive.
• Documented diagnosis of Congenital VWD, confirmed by laboratory testing consistent with ISTH/ASH) diagnostic guidelines).
• Vital signs are within normal ranges at Screening.
• Participants must meet the following baseline organ function, indicated by laboratory criteria as Screening:

• Renal: Estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73m\^2.
• Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin ≤1.5 upper limit of normal (ULN) at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN.
• Hematology >85 g/L and platelet count >120 x 10\^9/L.

Part A Only:

• Age: ≥18 and <70 years of age at the time of informed consent.
• VWD Subtype Eligibility:

• Cohorts A1 and A2: Participants with Type 1 VWD, only.
• Cohorts A3 and A4: Participants with Type 1 VWD (including Type 1C) and Type 2A VWD
• Residual VWF activity of ≤ 50 IU/dL and FVIII activity ≤ 70 IU/dL during screening.

Part B Only:

• Age: ≥16 and <70 years of age at the time of informed consent.
• VWD Subtype Eligibility: Participants with Type 1 VWD (including Type 1C) and Type 2A.
• Residual VWF activity of ≤50 IU/dL and FVIII activity ≤70 IU/dL during screening.
• Symptomatic Disease: Participants must be symptomatic, typically reporting bleeding events on a monthly basis.
• Bleeding History (must meet one of the following):

• Prior Observational Study Participation:

The participant must have participated in the observational study HMB-002-101\_SCR (VELORA Discover), have a minimum annualized treated bleeding event (ATBR) of 3; OR

• Medical Record-Documented Bleeding History:

The Investigator confirms that ≥3 treated bleeding events have been documented in the participant's medical record within the preceding 12 months.

Part C Only:

• Age: ≥18 and <70 years of age at the time of informed consent.
• Participants with Type 3 VWD or Type 1 VWD with low residual VWF and FVIII activity levels (VWF activity <5 IU/dL and FVIII activity <10 IU/dL).
• Receives regular VWF concentrate (at least 1/week) as part of their routine care (usual dose ≤50 IU/kg).

Критерии исключения

• Personal history of venous or arterial thrombosis or thromboembolic disease, except for catheter-associated, superficial venous thrombosis.
• High risk thrombophilia: Homozygous Factor V Leiden (FVL), compound heterozygous FVL/Prothrombin gene mutation, Antithrombin deficiency with activity <50%. Congenital Protein C and Protein S deficiency with levels <50%.
• Body mass index (BMI) >35 kg/m\^2 (obese, adjusted for ethnicity).
• Presence of other conditions that substantially increase risk of thrombosis either individually (for participants >65 years of age) or in combination (for participants ≤65 years of age), at the discretion of the Investigator or Medical Monitor.
• Clinically significant cardiovascular disease.
• Other known severe bleeding disorder(s) other than VWD.
• Requirement for concomitant medications that affect hemostasis (including, but not limited to anticoagulation, antiplatelet agents, certain non-steroidal anti-inflammatory drugs) and cannot refrain from use for 14 days prior to the first dose of study drug and throughout the study.

Exclusion Criteria for Part A and Part B Only

• Requirement for ongoing hemostatic treatment to prevent bleeding (bleed prophylaxis). Prophylaxis administered intermittently for procedures or surgery to reduce bleeding risk is permitted.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• Phoenix Children's Hospital — Phoenix
• Arkansas Children's Hospital — Little Rock
• Children's Hospital of Los Angeles — Los Angeles
• University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center — Miami
• Emory Children's Center — Atlanta
• Innovative Hematology, Inc./Indiana Hemophilia and Thrombosis Center — Indianapolis
• Tulane University School of Medicine — New Orleans
• University of Michigan Hospitals, Department of Hemophilia and Coagulation Disorders — Ann Arbor
• … и ещё 5 центров

Великобритания · 9 центров

• Basingstoke and North Hampshire Hospital — Basingstoke
• St George's Hospital — Tooting
• Royal London Hospital — Whitechapel
• University Hospitals Birmingham NHS Foundation Trust — Birmingham
• University Hospital of Wales — Cardiff
• St James's University Hospital, Leeds Haemophilia Centre — Leeds
• Royal Liverpool and Broadgreen University Hospitals NHS TRUST, The Roald Dahl Haemostasis — Liverpool
• Richmond Pharmacology — London
• … и ещё 1 центр

Австралия · 3 центра

• Fiona Stanley Hospital — Murdoch
• Royal Prince Alfred Hospital — Camperdown
• The Alfred Hospital — Melbourne

Идентификаторы

NCT: NCT06754852 · HMB-002-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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