Clinical trial NCT06297655: A Clinical Study of Recombinant Human Coagulation Factor VIII for Injection in Patients With Severe Hemophilia A
Official title: A Phase III Clinical Study Evaluating the Efficacy and Safety of On-demand Treatment and Perioperative Replacement Therapy With Recombinant Human Coagulation Factor VIII for Injection in Treated Severe Hemophilia A
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-03-07
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a single arm, open, multicenter clinical trial in which the previous treated severe hemophilia A patients receive recombinant human coagulation factor VIII for injection to evaluate the efficacy and safety of on-demand treatment in the event of new bleeding events. If evaluable surgical cases occur, the overall efficacy and safety of recombinant human coagulation factor VIII for injection as a replacement therapy for severe hemophilia A PTPs during the perioperative period will be evaluated.


Eligibility criteria: Inclusion Criteria:

* The subjects voluntarily joined this study, signed an informed consent form, and had good compliance;
* Age: ≥ 12 years old and ≤ 65 years old (when signing the informed consent form, if it is a minor, parents should sign on behalf of it);
* Severe hemophilia A (coagulation factor VIII activity\<1%), with exposure days (ED) of no less than 150 days prior to factor VIII (recombinant coagulation factor VIII or plasma derived coagulation factor VIII) treatment; Surgical patients need to have undergone at least 2 surgeries (including major surgeries) and plan to undergo elective surgery at the same time;
* The subjects must be HIV negative or have a viral load of \< 200 particles/μ, HIV positive patients with l or \< 400000 copies/ml.
* At baseline, no inhibitors were detected, and there was no history of Factor VIII inhibitor antibody formation (Bethesda method detection \< 0.6 BU/ml, test result record required);
* Subjects of childbearing age who agree to take effective contraceptive measures throughout the entire trial period and continue until 28 days after the last medication.

Exclusion Criteria:

* Known congenital or acquired hemorrhagic diseases other than hemophilia A;
* The subjects have used or planned to receive immunosuppressive treatments such as prednisone, cyclophosphamide, and cyclosporine in the week prior to enrollment, and are allowed to use inhaled or topical corticosteroids;
* Those who are known or suspected to have hypersensitivity reactions to the investigational drug, including human embryonic kidney cell protein;
* Significant liver and kidney dysfunction, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 5 upper limit of normal (ULN), and serum creatinine \>1.5 ULN;
* Hemoglobin \< 60 g/L;
* Expected to receive other drugs for the treatment of hemophilia A within 72 hours before the first administration (such as recombinant factor VIII, blood derived factor VIII, desmopressin, cryoprecipitate, plasma, etc.), or those who have used long-acting hemophilia A drugs for less than 5 half-lives before the first administration;
* Used within 14 days before the first administration or planned to use anticoagulants or antiplatelet drugs for treatment during clinical trials;
* Within 6 months prior to the first administration, use of Emicizumab;
* Serious cardiovascular and cerebrovascular diseases occurring within 6 months prior to the first administration, including but not limited to cerebral hemorrhage, cerebral infarction, unstable angina, malignant arrhythmia, acute myocardial infarction, congestive heart failure (New York Heart Association cardiac function classification ≥ III), and hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure 100 mmHg) that is poorly controlled despite treatment with one or more antihypertensive drugs;
* Participated in clinical trials of other drugs within 30 days prior to screening, or last used investigational drug with less than 5 half-lives;
* Alcohol abuse, drug abuse, mental disorders, and intellectual disabilities.

Primary outcomes:
measure: The proportion of on-demand treatment improvement for newly occurring bleeding events
timeFrame: For each new bleeding event, assessed within 72 hours after initial treatment
measure: Activity recovery
timeFrame: 15 minutes after infusion
Secondary outcomes:
measure: The proportion of effective surgical hemostasis
timeFrame: Within 72 hours after surgery
measure: Annualized bleeding rate (ABR)
timeFrame: Up to 180 days.
measure: The incidence of Less Han Expected Thermal Effect
timeFrame: For each new bleeding event, assessed within 24 hours after initial treatment
measure: The injection times of recombinant human coagulation factor VIII
timeFrame: Up to 180 days.
measure: The dosage of recombinant human coagulation factor VIII
timeFrame: Up to 180 days.
measure: Changes of Haemophilia Joint Health Score before and after on-demand treatment
timeFrame: Up to 180 days.
measure: Changes of Quality of Life Assessment before and after on-demand treatment
timeFrame: Up to 180 days.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drug Tower Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Tianjin
country: China
facility: Hematology Hospital of Chinese Academy of Medical Sciences
state: Tianjin
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
Study officials:
References: