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1225 A Phase 1/2, First-in-Human, Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants with Glanzmann Thrombasthenia

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Suthesh Sivapalaratnam, MD, PhD1*, Steve Austin, MD2*, Ulrike Lorch, MD, FRCA, FFPM3*, Thomas York, MD3*, Andrew Want, MBBS, PhD, FRCOphth3*, Ashley Gosnell, PA-C4*, Prafull S. Gandhi, PhD5*, Henrik Østergaard, PhD, MSc5*, Erik Bjornson5*, Tara O'Meara4*, Benny Sorensen, MD, PhD4, Roger E.G. Schutgens, MD, PhD, MSc6* and Catherine Rea, MD, PhD5*

1Queen Mary University of London, Blizard Institute, London, United Kingdom
2St. George's Hospital NHS Trust, London, GBR
3Richmond Pharmacology, London, United Kingdom
4Hemab Therapeutics, Cambridge, MA
5Hemab Therapeutics, Copenhagen, Denmark
6Center for Benign Hematology, Thrombosis and Hemostasis - Van Creveldkliniek, University Medical Center Utrecht, Utrecht, Netherlands

Background & Significance: Glanzmann thrombasthenia (GT) is a rare bleeding disorder resulting from a deficiency of integrin αIIbβ3 (also known as glycoprotein [GP] IIb/IIIa), a receptor for fibrinogen on platelets. Fibrinogen binding to αIIbβ3 bridges platelets and is a required step for normal platelet aggregation and hemostasis. GT is considered a severe bleeding disorder with approximately 50% of the patients reporting 1 bleed every day, and 13% reporting over 500 bleeds per year. The current standard of care for bleeding in patients with GT is reactive and on-demand, with no approved therapies for primary prophylaxis. HMB-001 is a bispecific antibody being developed by Hemab for prophylactic treatment to prevent and reduce bleeding events in patients with GT that can be administered subcutaneously. One arm of HMB-001 binds to and accumulates endogenous activated coagulation factor VII (FVIIa) while the second arm binds to the TREM-like transcript 1 receptor (TLT-1) on activated platelets. The combined effect of FVIIa accumulation and targeting to the surface of activated platelets via HMB-001 brings the activity of FVIIa to levels that are considered therapeutically effective based on clinical experience with recombinant FVIIa (rFVIIa). This is a first-in-human, Phase 1/2, dose escalation, safety, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy study of HMB-001 in participants with Glanzmann thrombasthenia.

Study Design and Methods:

The study consists of 3 parts.

  • Part A is a Phase 1, open-label, single ascending dose study, which will evaluate the safety, tolerability, PK, and PD of HMB-001 in participants with GT.
  • Part B is a Phase 2, open-label, multiple ascending dose study evaluating the safety, tolerability, PK, PD, and preliminary effects on bleeding of repeat doses of HMB-001 monotherapy.
  • Part C is a Phase 2, open-label, treatment extension portion study. It will be open to participants who have fulfilled the requirements of Part B and are considered eligible to continue by the Investigator. Part C will evaluate longer term safety, and preliminary efficacy of repeat doses of HMB-001 monotherapy for 9 months.

Study Population: Male and female participants 18 to 65 years of age with GT. Part A is single-center, while Part B/C will be a multicenter study in various countries.

Major inclusion and exclusion criteria include:

Criteria for Inclusion:

  • Part A and B
    • Age 18 to 65
    • Diagnosis of GT
    • Vital signs within normal range
    • Negative pregnancy test
    • Must meet the following baseline organ function
      • eGFR >45 mL/min/1.73m2
      • LFTs within normal range
      • Hgb >85 g/L and platelet count >150 x 109/L
    • Part B only
      • 2 bleeding events per week on average of any severity and type and at least 1 spontaneous or traumatic bleed within the last 12 months requiring treatment with rFVIIa, platelets, medical or surgical procedure

Criteria for Exclusion:

  • Part A
    • Active severe infection or inflammation
    • History of clinically significant hypersensitivity associated with monoclonal antibody therapies.
    • Personal or family history of venous or arterial thrombosis or thromboembolic disease.
    • Other risk factors that substantially increase risk of venous or arterial thrombosis
    • Congenital or acquired bleeding disorders other than GT
    • Concurrent disease, treatment, medications, or abnormality in clinical laboratory tests that may pose additional risk
    • Addiction or other diseases that prevent the participant from appropriately assessing the nature and scope of the clinical study or participating in study procedures

Participants included in Part B are eligible for Part C following completion of their dosing in Part B.

Disclosures: Schutgens: Bayer, CSL Behring, Hemab, NovoNordisk, Octapharma, Sanofi and Sobi: Research Funding.

*signifies non-member of ASH