Glanzmann Thrombasthenia
Conditions
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.
Interventions
DRUGHMB-001
HMB-001 is a bispecific antibody being developed as a prophylactic treatment option to prevent and reduce bleeding events in patients with Glanzmann thrombasthenia.
Sponsors
Hemab ApS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 67 Years
Healthy volunteers
No
Inclusion criteria
Part A Inclusion Criteria: 1. Age 18 to 65 years, at the time of signing informed consent. 2. Glanzmann thrombasthenia; documented abnormal, diagnostic platelet aggregometry plus deficiency of the αIIbβ3 (GPIIb/GPIIIa) receptor via flow cytometry; or genetic diagnosis. 3. Has the ability to provide informed consent. 4. Has an understanding, ability, and willingness to fully comply with trial procedures and restrictions. 5. Vital signs are within the following ranges at Screening: 1. Resting heart rate ≤ 105 bpm (after at least 5 minutes of resting). 2. 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. 6. Women of child-bearing potential (WOCBP) have a negative serum pregnancy test within 72 hours prior to the first dose of study drug. 7. WOCBP 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 study drug. 8. 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. 9. Participants must meet the following baseline organ function, indicated by laboratory criteria: 1. 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 2. 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 3. Hemoglobin \>85 g/L and platelet count \>120 x 10\^9/L at Screening. Part B Inclusion Criteria: 1. Has the ability to provide informed consent, and has an understanding, ability, and willingness to fully comply with clinical trial procedures and restrictions. 2. Age 18 to 65 years. 3. 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. 4. 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. 5. Vital signs are within the following ranges at Screening: 1. Resting heart rate ≤105 bpm (after at least 5 minutes of resting) 2. 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. 6. Women of child-bearing potential (WOCBP) have a negative serum pregnancy test within 72 hours prior to the first dose of study drug. 7. 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. 8. 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. 9. Participants must meet the following baseline organ function, indicated by laboratory criteria: 1. Evidence of no greater than mild to moderate reduction in renal function (stage 3a kidney disease), measured by an eGFR of ≥45 ml/min/1.73m2 at Screening. 2. An AST, ALT, and total bilirubin ≤1.5 ULN range at Screening. For participants with a history of Gilbert's Syndrome, total bilirubin ≤2 × ULN at Screening. 3. Hemoglobin \>85 g/L and platelet count \>120 x 10\^9/L at Screening. Part A
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Part A: PD parameters: Maximum, mean decrease from baseline in activated partial thromboplastin time (aPTT) | From baseline to Day 57 |
| Part B: Plasma concentrations of HMB-001 | From baseline to Day 106/ET/EOS |
| Part B: PK parameters: Cmax | From baseline to Day 106/ET/EOS |
| Part B: PK parameters: AUClast | From baseline to Day 106/ET/EOS |
| Part B: PK parameters: AUCinf | From baseline to Day 106/ET/EOS |
| Part B: PK parameters: Tmax | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by Subcategories of ABR, including, but not limited to spontaneous and impactful | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by Bleed Severity (occurrence of severe bleeding events) | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by the volume of transfusion product use | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by the Volume of FVIIa use | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by the Volume of red blood cell (RBC) transfusion | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by the Iron Status: Mean change in hemoglobin from baseline | From baseline to Day 106/ET/EOS |
| Part B: Preliminary prophylactic effect of HMB-001 as assessed by the Iron Status: Mean change in ferritin and total iron from baseline | From baseline to Day 106/ET/EOS |
| Part B: ADA formation | From baseline to Day 106/ET/EOS |
| Part B: Changes from baseline in Euro Quality of life 5-Dimensions 5-Level (EQ-5D-5L) score | From Baseline to Day 85/End of Treatment (EOT) |
| Part B: Changes from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 score | From Baseline to Day 85/End of Treatment (EOT) |
| Part B: Changes from baseline in Work Productivity and Activity Impairment (WPAI) score | From Baseline to Day 85/End of Treatment (EOT) |
| Part C: Plasma concentrations of HMB-001 | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: PK parameters: Cmax | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: PK parameters: AUClast | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: PK parameters: AUCinf | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: PK parameters: Tmax | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by Bleed Severity (occurrence of severe bleeding events) | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by the volume of transfusion product use | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by the Volume of FVIIa use | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by the Volume of red blood cell (RBC) transfusion | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by the Iron Status: Mean change in hemoglobin from baseline | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by the Iron Status: Mean change in ferritin and total iron from baseline | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| Part C: ADA formation | From baseline to Day 673/End of Treatment (EOT) |
| Part C: Changes from baseline in Euro Quality of life 5-Dimensions 5-Level (EQ-5D-5L) score | From baseline to Day 673/End of Treatment (EOT) |
| Part C: Changes from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 score | From baseline to Day 673/End of Treatment (EOT) |
| Part C: Changes from baseline in Work Productivity and Activity Impairment (WPAI) score | From baseline to Day 673/End of Treatment (EOT) |
| Part C: Preliminary prophylactic effect of HMB-001 as assessed by Bleeding Events | Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS) |
| 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 |
| Part A: Anti-drug antibody (ADA) formation | From baseline to Day 57 |
| Part A: PD parameters: Maximum, mean increase in Coagulation factor VII (FVII) from baseline | From baseline to Day 57 |
| Part A: PD parameters: Maximum, mean decrease from baseline in prothrombin time (PT) | From baseline to Day 57 |
Countries
Belgium, France, Italy, Netherlands, United Kingdom, United States
Outcome results
None listed