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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
California Clinical Trials Medical Group (CCTMG)
Glendale, California, United States
COMPLETEDChildren's Hospital Los Angeles
Los Angeles, California, United States
RECRUITINGRush University Medical Center
Chicago, Illinois, United States
NOT_YET_RECRUITINGLA Center for Bleeding and Clotting Disorders - Metairie
Metairie, Louisiana, United States
RECRUITINGUniversity of Michigan Hospitals - Michigan Medicine
Ann Arbor, Michigan, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGBrody School of Medicine at East Carolina University
Greenville, North Carolina, United States
NOT_YET_RECRUITINGPenn State Milton S Hershey Medical Center Pediatrics
Hershey, Pennsylvania, United States
NOT_YET_RECRUITINGPerelman Center for Advanced Medicine (PCAM)- Penn Blood Disorders Program
Philadelphia, Pennsylvania, United States
RECRUITINGMcMaster University Medical Centre, Hamilton Health Sciences
Hamilton, Ontario, Canada
RECRUITINGParts A and B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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.
Time frame: Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to 3 months
Parts A and B: Number of Participants with Clinical Abnormal Changes in Coagulations Markers
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.
Time frame: Part A: From Baseline (Day 1) till Day 57; Part B: From Baseline (Day 1) till Day 90
Part A: Area Under the Serum Concentration-time Curve from time Zero to the Last Quantifiable Time Point (AUC[0-t])
The PK profile (AUC\[0-t\]) of a single ascending SC dose of SR604 in healthy participants will be assessed.
Time frame: 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])
The PK profile (AUC\[0-inf\]) of a single ascending SC dose of SR604 in healthy participants will be assessed.
Time frame: From Baseline (Day 1) up to Day 57
Parts A and B: Maximum Concentration (Cmax) of SR604
The PK profile (Cmax) of a single ascending and multiple ascending SC dose of SR604 will be assessed.
Time frame: 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
The PK profile (tmax) of a single ascending and multiple ascending SC dose of SR604 will be assessed.
Time frame: Part A: From Baseline (Day 1) up to Day 57; Part B: From Baseline (Day 1) up to Day 90
Parts A and B: Terminal Half-life (T1/2) of SR604
The PK profile (T1/2) of a single ascending and multiple ascending SC dose of SR604 will be assessed.
Time frame: 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
The PK profile (CL/F) of a single ascending SC dose of SR604 in healthy participants will be assessed.
Time frame: From Baseline (Day 1) up to Day 57
Part A: Volume of Distribution in Terminal Phase Following Extravascular Administration (Vz/F) of SR604
The PK profile (Vz/F) of a single ascending SC dose of SR604 in healthy participants will be assessed.
Time frame: From Baseline (Day 1) up to Day 57
Parts B: Concentration before the next dose administration (Ctrough)
The PK profile (Ctrough) of SR604 following repeated SC injections will be assessed.
Time frame: From Baseline (Day 1) up to Day 90
Parts B: Accumulation Ratio (R) of SR604
The PK profile (accumulation R) of SR604 following repeated SC injections will be assessed.
Time frame: From Baseline (Day 1) up to Day 90
Parts B: Number of Bleeding Events
The preliminary clinical activity of SR604 will be assessed. Bleeding event (record traumatic or non-traumatic bleeding, number of bleeding sites \[joints or non-joints\], bleeding frequency (intervals), associated with any external triggers, level of physical activity) will be evaluated.
Time frame: From Baseline (Day 1) up to 3 months
Parts B: Annualized Bleeding Rate (ABR) in Body and Targeted Joints
The preliminary clinical activity of SR604 will be assessed. ABR in body and targeted joined will be evaluated.
Time frame: From Baseline (Day 1) up to 3 months
Parts A and B: Number of Participants with Positive Antidrug Antibodies (ADAs)
Number of participants with positive ADAs will be assessed.
Time frame: Part A: From Baseline (Day 1) till Day 57; Part B: From Baseline (Day 1) till Day 90
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