NCT06211634进行中（未招募）1 期
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
Hemab ApS17 个研究点 分布在 6 个国家目标入组 57 人开始时间: 2022年12月13日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 57
- 试验地点
- 17
- 主要终点
- Part A: Safety as assessed by the incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 67 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Participants must meet the following baseline organ function, indicated by laboratory criteria:
- •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
- •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
- •Hemoglobin >85 g/L and platelet count >120 x 10^9/L at Screening.
- •Part B Inclusion Criteria:
- •Has the ability to provide informed consent, and has an understanding, ability, and willingness to fully comply with clinical trial procedures and restrictions.
- •Age 18 to 65 years.
- •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.
- •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.
- •Vital signs are within the following ranges at Screening:
- •Resting heart rate ≤105 bpm (after at least 5 minutes of resting)
- •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 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.
- •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.
- •Participants must meet the following baseline organ function, indicated by laboratory criteria:
- •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.
- •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.
- •Hemoglobin >85 g/L and platelet count >120 x 10^9/L at Screening.
- •Part A Exclusion Criteria
- •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 study drug, post-partum within 12 weeks preceding first dose of study drug.
- •Women who are using estrogen-containing medication or hormone modulators (within 8 weeks pre-dose to 8 weeks post-dose of study drug).
- •Clinically significant cardiovascular disease.
- •Other conditions that substantially increase the risk of cardiovascular events by the discretion of the Investigator including, but not limited to: smoking, 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.
- •Addiction or other diseases that prevent the participant from appropriately assessing the nature and scope of the clinical study or participating in study procedures.
- •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 study drug.
- •Female participants who are pregnant or breastfeeding.
- •Part B Exclusion Criteria
- •Active severe infection or inflammation at the time of Screening or prior to the first dose of study drug.
- •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.
- •Co-existing thrombophilic disorder, as determined by the presence of any of the below (or via historical results, where available):
- 另有 16 项未显示
排除标准
- 未提供
研究组 & 干预措施
Single or Multiple ascending dose of HMB-001
Experimental
Open-label, single or multiple ascending dose of HMB-001
干预措施: HMB-001 (Drug)
结局指标
主要结局
Part A: Safety as assessed by the incidence of treatment-emergent adverse events (TEAEs)
时间窗: From baseline to Day 57
Part A: Safety as assessed by the changes in physical examinations, vital signs, clinical laboratory assessments, and ECG parameters
时间窗: From baseline to Day 57
Part B: Safety as assessed by the incidence of treatment-emergent AEs
时间窗: 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
时间窗: From baseline to Day 106/ET/EOS
Part B: Preliminary prophylactic effect of HMB-001 as assessed via Bleed frequency: annualized bleed rate (ABR)
时间窗: 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)
时间窗: From baseline to Day 106/ET/EOS
Part C: Safety as assessed by the incidence of treatment-emergent AEs
时间窗: 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
时间窗: 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)
时间窗: Day 99 to Day 687/Early Termination (ET)/ENdo of Study (EOS)
次要结局
- 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))
研究者
研究点 (17)
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