A Phase 1/2, First-in-Human, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of HMB-001 in Participants With Glanzmann Thrombasthenia
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Hemab ApS
- Enrollment
- 57
- Locations
- 17
- Primary Endpoint
- Part A: Safety as assessed by the incidence of treatment-emergent adverse events (TEAEs)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 67 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •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.
- •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.
Exclusion Criteria
- Not provided
Arms & Interventions
Single or Multiple ascending dose of HMB-001
Open-label, single or multiple ascending dose of HMB-001
Intervention: HMB-001 (Drug)
Outcomes
Primary Outcomes
Part A: Safety as assessed by the incidence of treatment-emergent adverse events (TEAEs)
Time Frame: From baseline to Day 57
Part A: Safety as assessed by the changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters
Time Frame: From baseline to Day 57
Part B: Safety as assessed by the incidence of treatment-emergent AEs
Time Frame: 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
Time Frame: From baseline to Day 106/ET/EOS
Part B: Preliminary prophylactic effect of HMB-001 as assessed via Bleed frequency: annualized bleed rate (ABR)
Time Frame: 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)
Time Frame: From baseline to Day 106/ET/EOS
Part C: Safety as assessed by the incidence of treatment-emergent AEs
Time Frame: 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
Time Frame: 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)
Time Frame: Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS)
Secondary Outcomes
- 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 extrapolated infinite time (AUCinf)(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: PD parameters: Maximum, mean decrease from baseline in activated partial thromboplastin time (aPTT)(From baseline to Day 57)
- Part A: PK parameters: Time to reach maximum observed plasma concentration (Tmax)(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 B: Plasma concentrations of HMB-001(From baseline to Day 106/ET/EOS)
- Part A: Anti-drug antibody (ADA) formation(From baseline to Day 57)
- Part A: PD parameters: Maximum, mean decrease from baseline in prothrombin time (PT)(From baseline to Day 57)
- Part B: PK parameters: Cmax(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 red blood cell (RBC) transfusion(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 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 B: PK parameters: AUClast(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: 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 the Volume of FVIIa use(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 C: PK parameters: AUCinf(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 B: Changes from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 score(From Baseline to Day 85/End of Treatment (EOT))
- Part C: PK parameters: Cmax(Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS))
- 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 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: PK parameters: AUClast(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: ADA formation(From baseline to Day 673/End of Treatment (EOT))
- 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 ferritin and total iron from baseline(Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS))
- 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: 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: 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 Work Productivity and Activity Impairment (WPAI) score(From baseline to Day 673/End of Treatment (EOT))