A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of SRSD107 in Healthy Chinese Subjects

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered SRSD107 in Healthy Subjects

This was a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneously administered SRSD107 in Chinese healthy subjects. SRSD107 is a synthetic, chemically modified double-stranded siRNA designed to silence hepatic FXI mRNA, thereby modulating coagulation.

Inclusion Criteria:

• Males or females, of any race, between 18 and 65 years of age, inclusive.
• Body mass index between 18.0 and 32.0 kg/square meter, inclusive.
• In good health, determined by no clinically significant findings from medical history, physical examination, clinical laboratory evaluations, 12 lead ECG, and vital signs measurements, at screening and check in, as assessed by the investigator (or designee).
• Activated partial thromboplastin time and prothrombin time within the normal reference range.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as pre-defined in the protocol.
• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.

Exclusion Criteria:

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• History or evidence of any abnormal bleeding or coagulation disorder; or evidence of coagulopathy, prolonged or unexplained, clinically significant bleeding, or frequent unexplained bruising or thrombus formation; or a history of spontaneous bleeding.
• Evidence of an active or suspected cancer, or a history of malignancy, within 5 years prior to screening. Nonmelanoma skin cancer, curatively treated localized prostate cancer, or other carcinoma in situ are not exclusionary, providing that they did not require systemic therapy and are considered cured.
• Acute of febrile illness within 7 days prior to dose administration or evidence of active infection.
• Any major surgery within 3 months prior to screening or plan to have any surgery during the study.
• History of clinically significant hypersensitivity, intolerance, or allergy to any drug compound, oligonucleotide, GalNAc, food, or other substance, as determined by the investigator (or designee).
• Systolic blood pressure >140 mmHg or <90 mmHg, or diastolic blood pressure >90 mmHg or <50 mmHg confirmed by repeat measurement.
• QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms confirmed by repeat measurement.
• Platelet count or hemoglobin level below the lower limit of normal.
• Alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, or total bilirubin >1.5 × the upper limit of normal.
• Estimated glomerular filtration rate <80 mL/min/1.73 square meter, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration equation.
• Positive hepatitis B and C, positive human immunodeficiency virus test or positive syphilis test. Subjects whose results are compatible with prior immunization may be included.
• Positive pregnancy test at screening or check in.
• Women who are menstruating at dosing, and women whose past volume of menstrual fluid was >80 mL or menstrual periods were >7 days.
• Use or intend to use any of the following, as determined by the investigator (or designee): 1) prescription medications/products or herbal products within 14 days or 5 terminal elimination half lives, whichever is longer, prior to dose administration in this study; 2) over the counter medications/products within 7 days prior to dose administration in this study. Recommended doses of vitamin and mineral supplements, over the counter analgesics (eg, paracetamol or ibuprofen for the treatment of acute conditions [eg, headache]), prescription oral, implantable, transdermal, injectable, or intrauterine contraceptives, and other products that have been approved by the investigator will not be exclusionary. Hormone replacement therapy will not be exclusionary, providing that the regimen has been stable for at least 2 months prior to screening and will not be changed during the study.
• Immunization with any live vaccine within 6 weeks prior to screening, or expected to require immunization with any live vaccine during the study.
• Receipt of an investigational drug in the past 90 days or 5 half lives of that drug, whichever is longer, prior to dosing in this study.
• Receipt of any siRNA treatment within 12 months or any antisense oligonucleotide treatment within 6 months prior to dosing in this study.
• Have previously completed or withdrawn from this study or any other study investigating SRSD107 and have previously received SRSD107.
• Drug abuse or addiction within 1 year prior to screening, as determined by the investigator (or designee).
• Positive alcohol or cotinine test result or positive urine drug screen (confirmed by repeat) at screening or check in.
• Regular alcohol consumption of >21 units per week for males and >14 units for females within 12 months prior to screening. One unit of alcohol equals 375 mL of beer or lager (3.5%), 100 mL of wine (13.5%), or 30 mL of spirits (40%).
• Use of tobacco or nicotine containing products within 1 months prior to screening.
• Receipt of blood products within 3 months prior to check in.
• Loss of >500 mL whole blood or donation of >200 mL blood products within 1 month prior to screening.
• History of intolerance to subcutaneous injections, or scarring (eg, from surgical procedures or burns) in areas when subcutaneous dose administration may occur.
• Poor peripheral venous access.
• Subjects who, in the opinion of the investigator (or designee), should not participate in this study.