A Study to Compare the Efficacy and Safety of SRSD107 and Enoxaparin in Adult Subjects Undergoing TKA

Official title

A Multicenter, Randomized, Open-Label, Blinded Endpoint Evaluation, Active Controlled Study to Compare the Efficacy and Safety of SRSD107 and Enoxaparin in Adult Subjects Undergoing Elective Primary Unilateral Total Knee Arthroplasty

Overview

This is a Phase 2, multicenter, randomized, open-label, parallel group, blinded endpoint evaluation, active-controlled, dose-finding study.This study is designed to compare the efficacy and safety of 3 dose levels of SRSD107 and enoxaparin 40 mg daily in subjects undergoing elective primary unilateral TKA.

Detailed description

This study is designed to compare the efficacy and safety of 3 dose levels of SRSD107 and enoxaparin 40 mg daily in subjects undergoing elective primary unilateral TKA. While the identity of the study drug will be unblinded, the specific dose of SRSD107 will be blinded. Up to approximately 450 subjects will be randomized.

Interventions

• Drug SRSD107
  SRSD107 is an investigational siRNA product for anticoagulants.
• Drug enoxaparin
  Enoxaparin is a low molecular weight heparin \[LMWH\] indicated for Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness.

Primary outcome measures

• Incidence of total venous thromboembolism (VTE) events [Time frame: From the date of surgery through 12±2 days after surgery.]

Secondary outcome measures (8)

• Incidence of major VTE [Time frame: From the date of surgery through 12±2 days after surgery and Day 64, respectively.]
• Incidence of total VTE events [Time frame: From the date of surgery through Day 64.]
• Incidence of total VTE events for each individual dosing cohort of SRSD107 compared to enoxaparin [Time frame: From the date of surgery through 12±2 days after surgery.]
• Incidence of composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) [Time frame: From the Pre-surgical Period through 12±2 days after surgery.]
• Incidence of composite of MB, CRNMB, and any bleeding [Time frame: From the Pre-surgical Period through 12±2 days after surgery, Day 64, and Day 169, respectively.]
• Incidence of MB [Time frame: From the Pre-surgical Period through 12±2 days after surgery.]
• Incidence of CRNMB [Time frame: From the Pre-surgical Period through 12±2 days after surgery.]
• Incidence of adverse events (AEs) [Time frame: From Day 1 through Day 169.]

Eligibility criteria

Inclusion criteria

• Able to provide written informed consent before any study assessment is performed.
• Male and female subjects, of any race, between 60 and 80 years of age, inclusive.
• Body mass index between 18.0 and 35.0 kg/m2, inclusive.
• Eligible to undergo elective primary unilateral TKA under general anesthesia.
• Willing to comply with study requirements including taking study drug at least 28 days prior to TKA, clinic visits, and venography at 10-14 days post TKA.
• aPTT, PT, and INR within the normal reference range at screening.

Exclusion criteria

• Active bleeding requiring medical or surgical intervention within 4 weeks prior to screening.
• Known bleeding disorder; history of increased bleeding tendency or any other condition that in the opinion of the investigator contraindicates prophylactic anticoagulation.
• History of intracranial, intraspinal, or intraocular bleeding.
• Evidence of active cancer, or a history of malignancy, within 2 years prior to screening.
• Myocardial infarction, DVT, PE, stroke , transient ischemic attack, systemic embolism, valvular thrombosis, or splanchnic thrombosis in the 6 months prior to screening.
• Uncontrolled blood pressure at the time of screening.
• Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2.
• Liver dysfunction, liver cirrhosis, history of hepatic encephalopathy, esophageal varices, or portocaval shunt.
• Clinically significant anemia at screening.
• Platelet counts <100,000/m3 at screening or a history of heparin-induced thrombocytopenia.
• Positive test for human immunodeficiency virus (HIV) , positive hepatitis B surface antigen, and/or active hepatitis C at screening.
• Ongoing or anticipated need for anticoagulation or antiplatelet therapy from 7 days prior to surgery through the EoS visit.
• Participation in an interventional clinical study within 5 half-lives of the investigational drug or 30 days prior to screening, whichever is longer.
• Use of any ASO or siRNA products within 1 year prior to screening. Diet and Lifestyle.
• Recent or current history of alcoholism or recreational drug abuse.
• History of hypersensitivity to any of the study drugs or its excipients, to drugs of similar chemical classes or drugs issued from the same biologic origin or any contraindication listed in the label for enoxaparin.
• Unable to undergo venography due to a known allergy to the contrast agent, anticipated poor venous access, impaired renal function, or any other reason identified and specified by the investigator.
• Anticipated elective surgery during the study period.
• Any other condition or circumstance that would affect the subject's ability to be compliant with study drug administration or study procedures, in the opinion of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Czechia · 1 center

• Hospital Nové Město na Moravě — Nové Město na Moravě

Identifiers

NCT: NCT07140523 · SRSD107-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗