A Phase 1/2 Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Glanzmann Thrombasthenia

NCT06211634 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HMB-001-CL101
• Study Type: interventional
• Target: 57
• Locations: 6 countries
• Sites: 17

Brief Summary

The goal of this clinical trial is to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia. The main questions it aims to answer are:

• Parts A, B, and C: To determine the safety and tolerability of HMB-001
• Part A: To establish the dose level(s) and dosing interval(s) of HMB-001 to be investigated in Parts B and C
• Parts B and C: To estimate the ability of HMB-001 to prevent the number and severity of bleeds Part A will assess differing singular doses of HMB-001 in small groups of participants. The dose administered to a newly enrolled participant (or groups of participants) may only increase if analysis of data from previous dosing shows it is safe to do so. The planned duration of participation in Part A is approximately 6 months, which consists of a Screening Period, an optional Run-in Observation Period, and a follow-up period of 8 weeks. Part B is similar to Part A as it involves testing different dose levels of HMB-001 in small groups of participants. However, in Part B, HMB-001 is given multiple times over a 3-month period, either weekly, every 2 weeks, or every 4 weeks. Part B consists of a Screening Period, a Run-in Observation Period, a 3-month Treatment Period, and a Safety Follow-up following the last dose of HMB-001. Part C is open to participants from Part B and consists of approximately a 18-month Treatment Period and a Safety Follow-up following the last dose of HMB-001.

Conditions

Glanzmann Thrombasthenia

Outcome Measures

Primary Outcomes (9)

• Part A: Safety as assessed by the incidence of treatment-emergent adverse events (TEAEs)

  From baseline to Day 57

• Part A: Safety as assessed by the changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters

  From baseline to Day 57

• Part B: Safety as assessed by the incidence of treatment-emergent AEs

  From baseline to Day 106/Early Termination (ET)/End of Study (EOS)

• Part B: Safety as assessed by the changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters

  From baseline to Day 106/ET/EOS

• Part B: Preliminary prophylactic effect of HMB-001 as assessed via Bleed frequency: annualized bleed rate (ABR)

  From baseline to Day 106/ET/EOS

• Part B: Preliminary prophylactic effect of HMB-001 as assessed via Bleed frequency: annualized treated bleed rate (ATBR)

  From baseline to Day 106/ET/EOS

• Part C: Safety as assessed by the incidence of treatment-emergent AEs

  Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS)

• Part C: Safety as assessed by the changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters

  Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS)

• Part C: Preliminary prophylactic effect of HMB-001 as assessed via Bleed frequency: annual treated bleed rate (ATBR) and annualized bleed rate (ABR)

  Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS)

Secondary Outcomes (41)

• Part A: Plasma concentrations of HMB-001

  From baseline to Day 57

• Part A: Pharmacokinetics (PK) parameters: Maximum observed plasma concentration (Cmax)

  From baseline to Day 57

• Part A: PK parameters: Area under the curve from time zero to last quantifiable concentration (AUClast)

  From baseline to Day 57

• Part A: PK parameters: Area under the curve from time zero to extrapolated infinite time (AUCinf)

  From baseline to Day 57

• Part A: PK parameters: Time to reach maximum observed plasma concentration (Tmax)

  From baseline to Day 57

Study Arms (1)

Single or Multiple ascending dose of HMB-001

EXPERIMENTAL

Open-label, single or multiple ascending dose of HMB-001

Drug: HMB-001

Interventions

HMB-001 DRUG

HMB-001 is a bispecific antibody being developed as a prophylactic treatment option to prevent and reduce bleeding events in patients with Glanzmann thrombasthenia.

Single or Multiple ascending dose of HMB-001

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years, at the time of signing informed consent.
• Glanzmann thrombasthenia; documented abnormal, diagnostic platelet aggregometry plus deficiency of the αIIbβ3 (GPIIb/GPIIIa) receptor via flow cytometry; or genetic diagnosis.
• Has the ability to provide informed consent.
• Has an understanding, ability, and willingness to fully comply with trial procedures and restrictions.
• Vital signs are within the following ranges at Screening:
• Resting heart rate ≤ 105 bpm (after at least 5 minutes of resting).
• Blood pressure (BP): Resting BP (after at least 5 minutes of resting or based on 24 hours monitor demonstrating normotensive BP): i. Systolic BP: 90 - 140 mmHg. ii. Diastolic BP: 40 - 90 mmHg.
• Women of child-bearing potential (WOCBP) have a negative serum pregnancy test within 72 hours prior to the first dose of study drug.

You may not qualify if:

• Men of child-producing potential agree to use highly effective contraceptive methods and avoid sperm donation for 14 days prior to Day 1, during the study treatment, and for 6 months after the last dose of study drug.
• Participants must meet the following baseline organ function, indicated by laboratory criteria:
• Evidence of no greater than mild to moderate reduction in renal function (stage 3a kidney disease), measured by an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73m2 at Screening
• An aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin ≤ 1.5 x upper limit of normal (ULN) range at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤ 2 × ULN at Screening
• Hemoglobin \>85 g/L and platelet count \>120 x 10\^9/L at Screening.
• Has the ability to provide informed consent, and has an understanding, ability, and willingness to fully comply with clinical trial procedures and restrictions.
• Age 18 to 65 years.
• Glanzmann thrombasthenia; Genetic diagnosis is required. Abnormal, diagnostic platelet aggregometry plus deficiency of the αIIbβ3 (GPIIb/GPIIIa) receptor via flow cytometry should be recorded if available.
• Patients should experience bleeding symptoms associated with Glanzmann Thrombasthenia defined as approximately two bleeding events per week of any severity and any type and at least one spontaneous or traumatic bleed that requires a prescribed treatment, medical or surgical procedure within the last 12 months.
• Vital signs are within the following ranges at Screening:
• Resting heart rate ≤105 bpm (after at least 5 minutes of resting)
• BP: Resting BP (after at least 5 minutes of resting or based on 24 hours monitor demonstrating normotensive BP): i. Systolic BP: 90 - 140 mmHg; ii. Diastolic BP: 40 - 90 mmHg.
• Women of child-bearing potential (WOCBP) have a negative serum pregnancy test within 72 hours prior to the first dose of study drug.
• WOCBP agree to use a highly effective contraceptive method and to avoid egg donation for 14 days prior to Day 1, during the study treatment, and for 6 months after the last dose of study drug. If utilizing an oral contraceptive, women must be on a stable dose of a non-estrogen-containing formulation for at least 8 weeks prior to the start of the Run-in Observation Period and for 8 weeks after the last dose of study drug.
• Men of child-producing potential agree to use highly effective contraceptive methods and avoid sperm donation for 14 days prior to Day 1, during the study treatment, and for 6 months after the last dose of study drug.

Sponsors & Collaborators

• Hemab ApS: lead

Study Sites (17)

University of California, San Diego (UCSD) (Part B/C)

La Jolla, California, 92093, United States

Location

Tulane University Medical Center (Part B/C)

New Orleans, Louisiana, 70112, United States

Location

Mayo Clinic - Rochester (Part B/C)

Rochester, Minnesota, 55905, United States

Location

Hemophilia Center of Western Pennsylvania (HCWP) (Part B/C)

Pittsburgh, Pennsylvania, 15213, United States

Location

Washington Institute for Coagulation (Part B/C)

Seattle, Washington, 98101, United States

Location

University Hospital Leuven - Campus Gasthuisberg (Part B/C)

Leuven, Belgium

Location

AP-HP Hopital Bicetre (Part B/C)

Le Kremlin-Bicêtre, France

Location

AP-HM - Hopital de la Timone

Marseille, France

Location

AP-HP Hopital Necker-Enfants Malades (Part B/C)

Paris, France

Location

Azienda Ospedaliero-Universitaria Careggi (Part B/C)

Florence, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano (Part B/C)

Milan, Italy

Location

Universitair Medisch Centrum Utrecht (Part B/C)

Utrecht, Netherlands

Location

Queen Elizabeth Hospital Birmingham (Part B/C)

Birmingham, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, United Kingdom

Location

Richmond Pharmacology Ltd (Part A/B/C)

London, United Kingdom

Location

Royal Free London NHS Foundation Trust (Part B/C)

London, United Kingdom

Location

The Royal London Hospital (Part B/C)

Whitechapel, United Kingdom

Location

MeSH Terms

Conditions

Thrombasthenia

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 18, 2024
• Study Start: December 13, 2022
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); NL (1); GB (5); FR (3); BE (1); IT (2)