A Clinical Study of Recombinant Human Coagulation Factor VIII for Injection in Patients With Severe Hemophilia A

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06297655
• Other study ID #: TQG202-III-01
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Lei Zhang, Doctor
• Phone: 13502118379
• Email: zhanglei1[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Drug:
• Recombinant human activated coagulation factor VIII for injection
Recombinant human coagulation factor VIII for injection is a recombinant DNA product with functional characteristics comparable to endogenous factor VIII.

Locations

Country	Name	City	State
China	Xiangya Hospital Central South University	Changsha	Hunan
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	Nanjing Drug Tower Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Hematology Hospital of Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Henan Tumor Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of on-demand treatment improvement for newly occurring bleeding events	Evaluate the hemostatic efficacy of the patient after each new bleeding event (including new bleeding events during visits and new bleeding events during home treatment), and calculate the proportion of improvement as excellent+good to the total number of on-demand treatment evaluations.	For each new bleeding event, assessed within 72 hours after initial treatment
Primary	Activity recovery	The activity of Recombinant human coagulation factor VIII measured at 15 minutes after infusion minus the baseline Recombinant human coagulation factor VIII activity divided by the expected improvement in Recombinant human coagulation factor VIII activity, which reflects the improvement in Recombinant human coagulation factor VIII levels after infusion.	15 minutes after infusion
Secondary	The proportion of effective surgical hemostasis	Assess the hemostatic efficacy of injecting recombinant human coagulation factor VIII during and after surgery. The effective ratio is the proportion of excellent or good to the total times of the surgical evaluation of hemostatic efficacy	Within 72 hours after surgery
Secondary	Annualized bleeding rate (ABR)	Including spontaneous and traumatic bleeding, as well as total bleeding; ABR can be calculated using the following formula: bleeding frequency/(treatment period days/365.25).	Up to 180 days.
Secondary	The incidence of Less Han Expected Thermal Effect	Without the influence of confounding factors, continuously infuse Recombinant human coagulation factor VIII twice within 24 hours for on-demand treatment, with no response to the same bleeding event.	For each new bleeding event, assessed within 24 hours after initial treatment
Secondary	The injection times of recombinant human coagulation factor VIII	The injection times of recombinant human coagulation factor VIII for each new bleeding event.	Up to 180 days.
Secondary	The dosage of recombinant human coagulation factor VIII	The dosage of recombinant human coagulation factor VIII (including average and total doses) for each new bleeding event	Up to 180 days.
Secondary	Changes of Haemophilia Joint Health Score before and after on-demand treatment	The scale assesses the functional status of the six major joints of the elbow, knee, and ankle, including: joint swelling, swelling duration, muscle atrophy, muscle strength, joint friction, joint pain, joint extension, joint flexion Degree decline, overall gait, etc.	Up to 180 days.
Secondary	Changes of Quality of Life Assessment before and after on-demand treatment	Quality of Life Assessment is a general questionnaire designed to measure health status on a scale of 0-100 with the higher value representing a better outcome and record the participants' current health state in 5 domains mobility, selfcare, usual activities, pain, anxiety.	Up to 180 days.