A Phase 1 Single and Multiple Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SR604 in Healthy Participants (Part A) and the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SR604 in Participants With Hemophilia A or Hemophilia B or Factor VII Deficiency (Part B)
概览
- 阶段
- 1 期
- 干预措施
- SR604
- 疾病 / 适应症
- 未指定
- 发起方
- Equilibra Bioscience LLC
- 入组人数
- 31
- 试验地点
- 17
- 主要终点
- Parts A and B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) of SR604 in healthy participants (Part A) and to evaluate the safety, tolerability, PK, PD, and efficacy of SR604 in participants with Hemophilia A or Hemophilia B, or Factor VII (FVII) deficiency, with or without inhibitors (Part B).
详细描述
This is a first-in-human (FIH) study to be conducted with SR604. The study will enroll healthy participants (Part A) and participants with Hemophilia A or Hemophilia B or FVII deficiency (Part B). In Part A (single ascending dose \[SAD\]): Healthy participants will be randomized in a 2:1 ratio in each of the 3 to 4 (Cohort 4 is optional) sequential cohorts. All cohorts will include participants receiving active treatment with SR604 and the other participant receiving matching placebo. In Part B (multiple ascending dose \[MAD\]): Participants with Hemophilia A or Hemophilia B or FVII deficiency, with or without inhibitors, will be enrolled in 4 cohorts with four dose levels and is planned to receive SR604 subcutaneously. The overall duration of study participation will be approximately 3 months.
研究者
入排标准
入选标准
- •Male participants aged 18 to 55 years, inclusive.
- •Body mass index between 18 and 30 kilograms per meter square (kg/m\^2), inclusive, and weighs greater than or equal to (\>=) 50 kilograms (kg), less than or equal to (\<=) 90 kg.
- •No clinically significant findings on medical examination, including physical examination, 12-lead electrocardiogram, and clinical laboratory tests.
- •Sexually active men must commit to use an effective method of birth control while taking the study intervention and for 90 days after the dose of study intervention.
- •Male and female participants (only female participants with congenital FVII deficiency) aged 18 to 60 years, inclusive.
- •Participants must have one of the following bleeding disorders: Severe hemophilia A (\<1% Factor VIII \[FVIII\]); or Severe and/or moderately severe Hemophilia B (≤ 2% Factor IX \[FIX\]); or Severe FVII deficiency (\<10% FVII activity). Participants with severe FVII deficiency must satisfy with either of following criteria:
- •Participants with history of \>2 bleeding events in the last 12 months require on-demand treatment with recombinant factor VIIa (rFVIIa) or plasma-derived FVII concentrates (pd-FVII) or fresh frozen plasma (FFP) for bleeding control.
- •Participants on prophylaxis treatment with rFVIIa or pd-FVII or FFP regardless of bleeding history.
- •Participants with Hemophilia A or Hemophilia B must satisfy either of the following criteria:
- •Participants not on prophylaxis must have a documented ABR of 6 in 12 months before screening.
排除标准
- •Participant has clinically significant history or evidence of cardiovascular, respiratory (including all chronic lung diseases), hepatic, renal, gastrointestinal, endocrine, neurological, immunological, bleeding, or psychiatric disorder(s).
- •Participant has a mean pulse less than (\<) 40 or greater than (\>) 90 beats per minute (bpm), mean systolic blod pressure (BP) \< 90 millimeter of mercury (mmHg) or \> 140 mmHg, or mean diastolic BP \< 50 mmHg or \> 90 mmHg at the screening visit.
- •Participant has a mean corrected QT corrected for heart rate by Fridericia's formula (QTcF) of \> 450 msec at the Screening Visit.
- •Participant has had injury, trauma, and/or major surgery within 3 months before Screening, or is planned to undergo surgery during the study.
- •Participant has received vaccination within 14 days before the dose of study intervention or has a vaccination planned during the study.
- •History of one or more of the following in participants and/or family members:
- •Factor V (FV) Leiden mutation.
- •Activated protein C (APC) resistant.
- •Protein C (PC) or protein S (PS) deficiency.
- •Prothrombin 20210 mutation;
研究组 & 干预措施
Part A: Cohort 1A (SR604 Dose 1)
Participants will receive single subcutaneous (SC) dose of SR604 dose 1 or matching placebo to SR604 on Day 1.
干预措施: SR604
Part A: Cohort 1A (SR604 Dose 1)
Participants will receive single subcutaneous (SC) dose of SR604 dose 1 or matching placebo to SR604 on Day 1.
干预措施: Placebo
Part A: Cohort 2A (SR604 Dose 2)
Participants will receive single SC dose of SR604 dose 2 or matching placebo to SR604 on Day 1.
干预措施: SR604
Part A: Cohort 2A (SR604 Dose 2)
Participants will receive single SC dose of SR604 dose 2 or matching placebo to SR604 on Day 1.
干预措施: Placebo
Part A: Cohort 3A (SR604 Dose 3)
Participants will receive single SC dose of SR604 dose 3 or matching placebo to SR604 on Day 1.
干预措施: SR604
Part A: Cohort 3A (SR604 Dose 3)
Participants will receive single SC dose of SR604 dose 3 or matching placebo to SR604 on Day 1.
干预措施: Placebo
Part A: Cohort 4A (SR604 Dose 4)
Participants will receive single SC dose of SR604 dose 4 or matching placebo to SR604 on Day 1.
干预措施: SR604
Part A: Cohort 4A (SR604 Dose 4)
Participants will receive single SC dose of SR604 dose 4 or matching placebo to SR604 on Day 1.
干预措施: Placebo
Part B: Cohort 1B (SR604 Dose 5)
Participants with Hemophilia A or Hemophilia B or FVII deficiency will receive SR604 dose 5 as multiple SC injections every 4-weeks.
干预措施: SR604
Part B: Cohort 2B (SR604 Dose 6)
Participants with Hemophilia A or Hemophilia B or FVII deficiency will receive SR604 dose 6 as multiple SC injections every 4-weeks.
干预措施: SR604
Part B: Cohort 3B (SR604 Dose 7)
Participants with Hemophilia A or Hemophilia B or FVII deficiency will receive SR604 dose 7 as multiple SC injections every 4-weeks.
干预措施: SR604
Part B: Cohort 4B (SR604 Dose 8)
Participants with Hemophilia A or Hemophilia B or FVII deficiency will receive SR604 dose 8 as multiple SC injections every 4-weeks.
干预措施: SR604
结局指标
主要结局
Parts A and B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to 3 months
Safety and tolerability of a single ascending SC dose of SR604 in healthy participants and multiple ascending SC doses of SR604 in participants with Hemophilia A or Hemophilia B or FVII deficiency will be evaluated.
Parts A and B: Number of Participants with Clinical Abnormal Changes in Coagulations Markers
时间窗: Part A: From Baseline (Day 1) till Day 57; Part B: From Baseline (Day 1) till Day 90
Safety and tolerability of a single ascending SC dose of SR604 in healthy participants and multiple ascending SC doses of SR604 in participants with Hemophilia A or Hemophilia B or FVII deficiency will be evaluated.
次要结局
- Part A: Area Under the Serum Concentration-time Curve from time Zero to the Last Quantifiable Time Point (AUC[0-t])(From Baseline (Day 1) up to Day 57)
- Part A: Area Under the Serum Concentration-time Curve from time Zero Extrapolated to Infinity (AUC[0-inf])(From Baseline (Day 1) up to Day 57)
- Parts A and B: Maximum Concentration (Cmax) of SR604(Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to Day 90)
- Parts A and B: Time to Maximum Concentration (tmax) of SR604(Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to Day 90)
- Part A: Clearance Following Extravascular Administration (CL/F) of SR604(From Baseline (Day 1) up to Day 57)
- Parts A and B: Terminal Half-life (T1/2) of SR604(Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to Day 90)
- Part A: Volume of Distribution in Terminal Phase Following Extravascular Administration (Vz/F) of SR604(From Baseline (Day 1) up to Day 57)
- Parts B: Concentration before the next dose administration (Ctrough)(From Baseline (Day 1) up to Day 90)
- Parts B: Accumulation Ratio (R) of SR604(From Baseline (Day 1) up to Day 90)
- Parts B: Number of Bleeding Events(From Baseline (Day 1) up to 3 months)
- Parts B: Annualized Bleeding Rate (ABR) in Body and Targeted Joints(From Baseline (Day 1) up to 3 months)
- Parts A and B: Number of Participants with Positive Antidrug Antibodies (ADAs)(Part A: From Baseline (Day 1) till Day 57; Part B: From Baseline (Day 1) till Day 90)