Glanzmann thrombasthenia Not Applicable
Conditions
Interventions
The clinical trial is made up of the following parts:
Screening visit: Participants will be required to attend a screening visit scheduled within 28 days before the start of the clinical trial. Scree
Sponsors
Richmond Pharmacology Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged 18 to 65 years, inclusive, at the time of signing informed consent 2. Glanzmann thrombocythemia: 2.1. Documented abnormal, diagnostic platelet aggregometry plus deficiency of the aIIbß3 (GPIIb/GPIIIa) receptor via flow cytometry 2.2. Genetic diagnosis 3. Has not received a COVID-19 vaccine dose in the last 28 days. Has not received any live vaccine within 4 weeks of enrollment and is not planning to have a live vaccine during the study period. 4. Agrees to not receive COVID-19 vaccination throughout the dosing period and for 4 weeks after the final dose. 5. Has the ability to provide written, personally signed and dated informed consent to participate in the trial, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and applicable regulations, before completing any trial-related procedures. 6. Has an understanding, ability, and willingness to fully comply with trial procedures and restrictions. 7. Women of child-bearing potential have a negative serum pregnancy test within 72 hours prior to the first dose of HMB-001. 8. Women of child-bearing potential agree to use highly effective contraceptive methods (excluding estrogen containing combined oral contraceptive pill as per exclusion criteria) and avoid egg donation for 14 days prior to Day 1, during the study treatment, and for 6 months after the last dose of HMB-001. A woman is considered to be of child-bearing potential unless she: 8.1. Has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; 8.2. Is aged 50 years old and over and has been amenorrhoeic for = 12 months (including no irregular menses or spotting) in the absence of any medication which induces a menopausal state and has documented ovarian failure by serum estradiol and follicle-stimulating hormone levels within the institutional laboratory postmenopausal range). 9. 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 HMB-001. A man is considered to be of child-producing potential unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.
Exclusion criteria
Exclusion criteria: 1. Severe infection or inflammation at the time of Screening 2. History of clinically significant hypersensitivity associated with monoclonal antibody therapies 3. Personal history of venous or arterial thrombosis or thromboembolic disease 4. Known severe congenital or acquired thrombophilia 5. Has vital signs outside of the following normal range at Screening: 5.1 Supine heart rate 30 kg/m2 (moderately obese, adjusted for ethnicity), reduced mobility, active malignancy, major surgery within 6 weeks preceding first dose of study drug, post-partum within 12 weeks preceding first dose of study drug 10. Women who are using estrogen-containing medication or hormone modulators (within 8 weeks pre dose to 8 weeks post dose of study drug) including: 10.1. Combined oral contraception pill 10.2. Hormone replacement therapy (excluding transdermal patches) 10.3. Oestrogen receptor modulators (eg, Tamoxifen) 10.4. Gonadotropin releasing hormone receptor (GnRH receptor) agonist 11. 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 ischaemic stroke. 12. Other conditions that substantially increase risk of cardiovascular events by the discretion of the Investigator including, but not limited to: smoking, cocaine use, and uncontrolled hypertension. 13. Congenital or acquired bleeding disorders other than Glanzmann thrombocythemia. 14. 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. 15. 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. 16. Received investigational medication in another clinical study within 5 half-lives before administration of the study drug. 17. Female participants who are pregnant (including a positive serum pregnancy test at Screening) or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: 1. Safety assessed by the incidence of treatment-emergent adverse events (AEs) and changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters. Part B: 2. Safety assessed by the incidence of treatment-emergent AEs and changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters 3. Preliminary prophylactic effect of HMB-001 as assessed via: 3.1. Frequency of major bleeds (defined as bleeding events requiring pharmacological treatment, transfusion, or surgical/interventional radiology intervention) 3.2. Frequency of minor bleeds (all other bleeding and bruising events) 3.3. Transfusion product use: Red blood cell, platelets, fresh frozen plasma, cryoprecipitate 3.4. Mean change in hemoglobin from baseline 3.5. Iron replacement therapy requirements: intravenous or oral 3.6. Factor Concentrate Use: Recombinant FVIIa 3.7. Tranexamic acid use On Day 1 of their in-clinic stay, participants of Part A will receive a single dose of HMB-001 treatment and will then be monitored for safety by AE reporting, physical examinations, vital signs, laboratory tests, and ECGs. Blood samples for systemic PK and PD biomarkers will be collected. All AEs and SAEs will be recorded. Bleeding events will be recorded continuously using a custom-designed electronic application. Safety will be evaluated on an ongoing basis throughout the study. From the signing of informed consent, all SAEs and study procedure-related AEs will be recorded. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: 1. Plasma concentrations of HMB-001 2. PK parameters including, but not limited to: 3. Maximum observed plasma concentration (Cmax) 3.1. Area under the curve from time zero to last quantifiable concentration (AUClast) 3.2. Incremental recovery (IncRec) 3.3. Area under the curve from time zero to extrapolated infinite time (AUCinf) 3.4. Time to reach maximum observed plasma concentration (Tmax) 4. Pharmacodynamic parameters including, but not limited to: 4.1. Maximum mean increase in FVII from baseline 4.2. Maximum mean decrease from baseline in prothrombin time (PT) 4.3. Maximum mean decrease from baseline in activated partial thromboplastin time (aPTT) 5. Preliminary prophylactic effect of HMB-001 as assessed via: 5.1 Frequency of major bleeds (defined as bleeding events requiring pharmacological treatment, transfusion, or surgical/interventional radiology intervention) 5.2 Frequency of minor bleeds (all other bleeding and bruising events) 5.3 Transfusion product use: Red blood cells, platelets, fresh frozen plasma, cryoprecipitate 5.4 Mean change in hemoglobin from baseline 5.5 Factor Concentrate Use: Recombinant FVIIa 5.6 Tranexamic acid use 6. Anti-drug antibody (ADA) formation Part B: 7. Plasma concentrations of HMB-001 8. PK parameters including, but not limited to: 8.1. Cmax 8.2. AUClast 8.3. IncRec 8.4. AUCinf 8.5. Volume of distribution at steady state (Vss) 8.6. Tmax 9. ADA formation 10. Changes from Baseline in QOL assessment scores Participants in Part B will receive multiple doses of HMB-001 treatment at intervals defined in Part A for a 3-month period beginning on Day 1 and will be monitored for safety by AE reporting, physical examinations, vital signs, laboratory tests, and ECGs. Blood samples for systemic PK and PD biomarkers will be collected. All AEs and SAEs will be recorded. Bleeding events will be recorded continuously using a custom-designed electronic application. | — |
Countries
France, Netherlands, United Kingdom
Outcome results
None listed