A Phase 1 Study to Evaluate the Safety, Tolerability, PK/PD of SRSD107 in Healthy Participants

Sirius Therapeutics

Status and phase: Completed; Phase 1

Conditions: Thrombosis

Treatments: Drug: Placebo; Drug: SRSD107

Study type: Interventional

Funder types: Industry

Identifiers

NCT06116617

SRSD107-101

Details and patient eligibility

About

The primary aim of this study is to evaluate safety and tolerability data when SRSD107 is administered as single SC injections to healthy participants. This information, along with PK/PD data, will help establish the appropriate doses and dosing regimen for future studies in patients.

Full description

SRSD107 is a synthetic, chemically modified double-stranded, small interfering ribonucleic acid (siRNA). The antisense strand is specifically designed to recognize and cleave human factor XI (FXI) messenger ribonucleic acid (mRNA) which reduces FXI protein. FXI protein reduction may prevent thromboembolic events without increasing the risk of bleeding.

This study will be a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study conducted in two parts. A total of 40 participants will be studied in 5 groups (Groups A1 to A5), each group consisting of 8 participants. In each group, 6 participants will receive SRSD107 and 2 will receive a placebo.

Enrollment: 40 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Body mass index between 18.0 and 32.0 kg/m2, inclusive.
• In good health, based on no clinically significant findings from medical history, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations.
• Activated partial thromboplastin time and PT within the normal range.
• Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Able to understand 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).
• Confirmed systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg.
• QT interval corrected for heart rate using Fridericia's method (QTcF) >450 ms in males or >470 ms in females confirmed by repeat measurement.
• White blood cell count <3.5 × 109/L, platelets <100 × 109/L, or hemoglobin 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 (ULN).
• Estimated glomerular filtration rate <80 mL/min/1.73m2, as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration equation.
• Positive hepatitis panel and/or positive human immunodeficiency virus test.
• Positive pregnancy test at screening or check in.
• Receipt of blood products within 2 months prior to check in.
• Loss of >500 mL whole blood or donation of blood products within 1 month prior to screening.
• History of intolerance to SC injections, or scarring (eg, from surgical procedures or burns) in areas when SC dose administration may occur.
• Participants who, in the opinion of the investigator (or designee), should not participate in this study.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

SRSD107

Experimental group

Description:

SRSD107 for subcutaneous (s.c.) injection Group A1, 15mg, single dose Group A2, 45mg, single dose Group A3, 120mg, single dose Group A4, 240mg, single dose Group A5, 450mg, single dose

Treatment:

Drug: SRSD107

Placebo

Placebo Comparator group

Description:

Sodium chloride for subcutaneous (s.c.) injection

Treatment:

Drug: Placebo