A Phase II Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetics of SR604 Injection in Patients With Von Willebrand Disease

Official title

A Multi-Dose, Randomized, Multicenter Phase II Clinical Trial to Evaluate the Efficacy, Safety, and Pharmacokinetic Profile of SR604 Injection in Patients With Von Willebrand Disease

Overview

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamic (PD) of SR604 in patients with von Willebrand disease.

Interventions

• Drug SR604
  SR604 will be administered as SC injection.

Primary outcome measures

• Total annualized bleeding rate (ABR) after treatment [Time frame: From baseline, through study completion, an average of 52 weeks]

Secondary outcome measures (12)

• Annualized spontaneous bleeding rate [Time frame: From baseline, through study completion, an average of 52 weeks]
• Annualized traumatic bleeding rate [Time frame: From baseline, through study completion, an average of 52 weeks]
• Overall annualized bleeding rate, annualized spontaneous bleeding rate, and annualized traumatic bleeding rate [Time frame: From baseline, through study completion, an average of 52 weeks]
• EQ-5D-5L health questionnaire utility value [Time frame: From baseline, through study completion, an average of 52 weeks]
• Change in EQ-VAS score from baseline [Time frame: From baseline, through study completion, an average of 52 weeks]
• PK parameters after first dose:Peak Plasma Concentration (Cmax) [Time frame: Day1]
• Pharmacokinetic parameters after multiple doses: Peak Plasma Concentration (Cmax) [Time frame: From baseline, through study completion, an average of 52 weeks]
• Incidence of Adverse Events (AEs) [Time frame: From baseline, through study completion, an average of 52 weeks]
• PK parameters after first dose:Time to Peak Plasma Concentration (Tmax) [Time frame: Day1]
• Safety: Number and incidence of patients with anti-drug antibodies (ADA) [Time frame: From baseline, through study completion, an average of 52 weeks]
• Pharmacokinetic parameters after multiple doses: Time to Peak Plasma Concentration (Tmax) [Time frame: From baseline, through study completion, an average of 52 weeks]
• Incidence of Serious Adverse Events (SAEs) [Time frame: From baseline, through study completion, an average of 52 weeks]

Eligibility criteria

Inclusion criteria

• Patients must meet ALL of the following inclusion criteria to be enrolled:

• Age >= 18 years and <= 65 years at the time of signing informed consent, regardless of sex;
• At screening, patients with a confirmed diagnosis of von Willebrand disease (VWD) with documented evidence and a defined VWD subtype;
• At least 4 new bleeding episodes within 6 months prior to screening;
• No active bleeding symptoms prior to the first dose;
• The subject or impartial witness fully understands and is able to comply with the protocol requirements, is willing to complete the study as planned, and voluntarily agrees to provide biological samples for testing as required by the protocol; is able to understand the procedures and methods of this clinical trial, provides voluntary participation after full informed consent, and personally signs the informed consent form.

Exclusion criteria

• Patients meeting ANY of the following exclusion criteria will not be enrolled:

• Known history of hypersensitivity to the investigational drug formulation or any of its components;
• Intolerance to subcutaneous injection or presence of other local skin abnormalities or dermatological conditions that may affect drug administration and safety assessment;
• Meeting any of the following criteria at screening:

• Hemoglobin < 60 g/L;
• Platelet count < 80 x 10\^9/L;
• Hepatic or renal dysfunction: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 2.5 x upper limit of normal (ULN), or total bilirubin >= 1.5 x ULN; or serum creatinine (Cr) >= 1.5 x ULN;
• Positive for anti-human immunodeficiency virus (HIV) antibody;
• Presence of any bleeding disorder other than von Willebrand disease \[hemophilia A or B, congenital coagulation factor VII deficiency, acquired von Willebrand disease (AVWS), platelet-type VWD, inherited platelet disorders, etc.\]; or significantly abnormal coagulation parameters due to diseases other than von Willebrand disease (e.g., platelet disorders, vitamin K deficiency, etc.);
• Presence of protein C deficiency or protein S deficiency;
• History of thrombosis or family history of thrombosis prior to signing informed consent or currently, or history of thrombophilia;
• Severe bleeding due to VWD within 2 years prior to screening, such as intracranial hemorrhage, esophageal variceal bleeding, etc.;
• Severe cardiac disease, such as unstable angina, congestive heart failure (New York Heart Association class >= III), severe arrhythmia (QTc interval > 500 ms, corrected by Fridericia formula), uncontrolled hypertension (systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg), etc.;
• Female patients with menstrual abnormalities due to organic gynecological diseases (e.g., uterine fibroids, endometriosis, adenomyosis, etc.);
• Previous or current life-threatening malignant neoplasms or end-stage liver disease;
• Use of DDAVP or plasma-derived VWF-containing factor VIII concentrate, plasma-derived/recombinant VWF preparations, or antifibrinolytic therapy within 1 week prior to the first dose;
• Use of antithrombotic agents within 1 week prior to the first dose;
• Receipt of fresh blood/plasma or cryoprecipitate therapy within 2 weeks prior to the first dose;
• Receipt of vaccination within 1 month prior to the first dose or planned vaccination during the study period;
• Major surgery (major surgery defined as Grade III and IV surgeries) within 1 month prior to the first dose, or planned surgery during the study period;
• Enrollment in other clinical trials within 1 month prior to the first dose;
• History of drug abuse or alcohol dependence (alcohol dependence criteria: long-term drinking history exceeding 5 years, equivalent ethanol intake >= 40 g/day, or heavy drinking within 2 weeks, equivalent ethanol intake > 80 g/day. Ethanol amount (g) conversion formula = alcohol consumption (mL) x alcohol content (%) x 0.8);
• Presence of psychiatric disease or significant mental disorder, or other reasons resulting in incapacity or lack of cognitive ability;
• Plans for procreation or sperm donation throughout the study period up to 3 months after the last dose, or unwillingness to use effective physical contraceptive measures (e.g., condoms);
• Presence of clinically significant disease or other reasons rendering the patient unsuitable for clinical trial participation in the investigator's opinion (e.g., patient unlikely to benefit from the clinical trial);
• Patients whom the investigator considers to have poor compliance, rendering efficacy evaluation difficult or likelihood of completing the planned treatment course and follow-up low.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 9 centers

• Xiangya Hospital of Central South University — Changsha
• The First Affiliated Hospital of University of Science and Technology of China — Hefei
• Jinan Central Hospital — Jinan
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• The First Affiliated Hospital of Soochow University — Suzhou
• The Second Hospital of Shanxi Medical University — Taiyuan
• North China University of Science and Technology Affiliated Hospital — Tangshan
• Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences — Tianjin
• … and 1 more center

Identifiers

NCT: NCT07640893 · LS-SR604-VWD-II01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗