Safety, Tolerability, PK, PD, and Efficacy of HMB-001 in Participants With Glanzmann Thrombasthenia

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• 1. Part A • Each participant in Part A must not meet any of the following exclusion criteria to be eligible for enrolment in the study: Severe infection or inflammation at the time of Screening. History of clinically significant hypersensitivity associated with monoclonal antibody therapies. Personal history of venous or arterial thrombosis or thromboembolic disease, with the exception of catheter-associated, superficial vein thrombosis. Known severe congenital or acquired thrombophilia. Has a positive test for Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at Screening with RNA level above the lower limit of detection. Participants with a positive test for HCV Ab may be included if they have a negative RNA test, consistent with cleared infection. Participants with an HIV RNA level lower than the limit of detection may be included. Other conditions that substantially increase risk of thrombosis by the discretion of the investigator including, but not limited to: significant family history, body mass index (BMI) >30 kg/m2 (moderately obese, adjusted for ethnicity), reduced mobility, active malignancy, major surgery within 6 weeks preceding first dose of HMB-001, post-partum within 12 weeks preceding first dose of HMB-001. Women who are using estrogen-containing medication or hormone modulators (within 8 weeks pre-dose to 8 weeks post-dose of HMB-001) including: Women on combined oral contraception with estrogen >3030 μg Women on combined oral contraception with estrogen < 30 μg during the study must not meet any of the following restrictions: Combined oral contraception not established for a minimum of 12 months of continuous use (week off per month for breakthrough bleeding allowed) prior to first dose of HMB-001. Intention to change or interrupt contraceptives use during study. Hormone replacement therapy (excluding transdermal patches). Estrogen receptor modulators (e.g., Tamoxifen). Gonadotropin releasing hormone receptor (GnRH receptor) agonist. Clinically significant cardiovascular disease including, but not limited to: New York Heart Association Class III or IV heart failure, coronary artery disease, uncontrolled arrythmia, moderate to severe valvular heart disease, peripheral vascular disease, and ischemic stroke. Other conditions that substantially increase the risk of cardiovascular events by the discretion of the Investigator including, but not limited to: age, obesity, immobility, moking, cocaine use, and uncontrolled hypertension. Congenital or acquired bleeding disorders other than Glanzmann thrombasthenia. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests that may pose additional risk in the opinion of the investigator and preclude the participant’s safe participation in and completion of the study. Addiction or other diseases that prevent the participant from appropriately assessing the nature and scope of the clinical study or participating in study procedures by the discretion of the Investigator. Received any live vaccine within 4 weeks of enrollment or is planning to have a live vaccine during the study period. Received investigational medication in another clinical study within 5 half-lives before administration of HMB-001. Female participants who are pregnant (including a positive serum pregnancy test at Screening) or breastfeeding. Participants who initially failed due to temporary non-medically significant issues are eligible for re-screening once the cause has resolved.
• 2. Part B • Each participant in Part B must not meet any of the following exclusion criteria to be eligible for enrolment in the study: Active severe infection or inflammation at the time of Screening or prior to the first dose of HMB-001. History of clinically significant hypersensitivity associated with monoclonal antibody therapies. Personal history of venous or arterial thrombosis or thromboembolic disease, with the exception of catheter-associated, superfcial vein thrombosis. Has known, documented, high risk congenital thrombophilia. Family history of unprovoked venous thrombosis in first degree relative. Has a positive test for HbsAg, HCV Ab, or HIV Ab at Screening with RNA level above the lower limit of detection. Participants with a positive test for HCV Ab may be included if they have a negative RNA test, consistent with cleared infection. Participants with an HIV RNA level lower than the limit of detection may be included. Other conditions that substantially increase risk of thrombosis by the discretion of the investigator including, but not limited to: BMI >30 kg/m2 (moderately obese, adjusted for ethnicity), reduced mobility, active malignancy major surgery within 6 weeks preceding first dose of HMB-001, post-partum within 12 weeks preceding first dose of HMB-001. Women who are using estrogen-containing medication or hormone modulators from 8 weeks prior to the first dose of HMB-001 until 8 weeks after the last dose of HMB-001 Women on combined oral conraception with estrogen dose > 30 μg Women on combined oral contraception with estrogen < 30 μg during the study must not meet any of the following restrictions: Combined oral contraception not established for a minimum of 12 months of continuous use (week off for breakthrough bleeding allowed)at time of screening Intention to change or interrupt contraceptive use during study: Hormone replacement therapy (excluding transdermal patches) Estrogen receptor modulators (e.g., Tamoxifen) GnRH receptor agonist. Clinically significant cardiovascular disease including, but not limited to: New York Heart Association Class III or IV heart failure, coronary artery disease, uncontrolled arrythmia, moderate to severe valvular heart disease, peripheral vascular disease, and ischemic stroke. Other conditions that substantially increase risk of cardiovascular events by the discretion of the Investigator including, but not limited to: current and previous smoking history, age, obesity, immobility, cocaine use, uncontrolled hypertension and untreated hyperlipidemia. Congenital or acquired bleeding disorders other than Glanzmann thrombasthenia. Concurrent disease, treatment, medication, or abnormality in clinical laboratory tests that may pose additional risk in the opinion of the investigator and preclude the participant’s safe participation in and completion of the study. Addiction or other diseases that prevent the participant from appropriately assessing the nature and scope of the clinical study or participating in study procedures by the discretion of the Investigator. Received any live vaccine within 4 weeks of enrollment or is planning to have a live vaccine during the study period. Received investigational medication in another clinical study within 5 half-lives before administration of HMB-001. Female participants who are pregnant (including a positive serum pregnancy test at Screening or breastfeeding. Participants who initially failed due to temporary non-medically significant issues are eligible for re-screening once the cause has resolved.
• 3. Part B and Part C • Participants included in Part B are eligible for Part C following completion of their Day 85 Visit provided they fulfilled the requirements of Part B (including acceptable compliance), are considered suitable to continue by the Investigator, have not met individual stopping rules, and provide consent. If the participant experiences a toxicity that does not meet individual stopping criteria, symptoms must have resolved to Grade 1 or baseline prior to commencing dosing in Part C.
• 4. Part B Co-existing thrombophilic disorder, as determined by the presence of any of the below (or via historical results, where available): • Homozygous for Factor V Leiden gene mutation • Compound heterozygous for Factor V Leiden gene mutation • Prothrombin G20210A mutation • Antithrombin III, Protein C deficiency or Protein S deficiency with activity levels of ≤50% in participants with at least 1 second-degree relative with an unprovoked venous thromboembolism (VTE), or a first-degree relative with a minimally provoked VTE or at Investigator discretion for participants with an unknown family history