- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05707351
A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A
A Phase 3, Prospective, Multicenter, Open-label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (ADYNOVATE) Administered for Prophylaxis and Treatment of Bleeding in Chinese Previously Treated Patients With Severe Hemophilia A (FVIII <1%)
The main aim of the study is to determine how well Adynovate works to decrease bleeding in previously treated Chinese men and boys with severe hemophilia A when given prophylactically.
Participants will be treated with Adynovate twice a week for 26 weeks or until participants have received 50 days of treatment with Adynovate (whichever takes longer). Participants will need to visit their study clinic several times during their participation.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Takeda Contact
- Phone Number: +1-877-825-3327
- Email: medinfoUS@takeda.com
Study Locations
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Beijing, China
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
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Beijing, China
- Beijing Children's hospital, Capital Medical University
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Changsha, China
- Xiangya Hospital of Central South University
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Fuzhou, China
- Fujian Medical University Union Hospital
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Guangzhou, China
- Nanfang Hospital Southern Medical University
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Hefei, China
- Anhui Province Hospital
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Jinan, China
- Jinan Central Hospital
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Shenzhen, China
- Shenzhen Second People's Hospital
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Suzhou, China
- The First Affiliated Hospital of Soochow University
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Tianjin, China
- Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
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Wuhan, China
- Union Hospital Tongji Medical College Huazhong University of science and Technology
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Wuhan, China
- Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Participant and/or legally authorized representative must voluntarily sign a written informed consent form (ICF) after all relevant aspects of the study have been explained and discussed with the Participant. For the participants less than (<) 18 years old, participants will give assent AND their parents/legally authorized representative should sign the ICF accordingly.
- Participant and/or legally authorized representative understands and is willing and able to comply with all requirements of the study protocol.
- Participant should be ethnic Chinese.
- Participant is 12 to 65 years of age at screening and male.
- Participant has severe hemophilia A (FVIII clotting activity <1 percent [%]) as confirmed by the central laboratory at screening after a washout period of at least 72 to 96 hours.
- The last on-demand or prophylactic treatment received is within 3 months before screening.
- Participant has documented previous treatment with plasma-derived FVIII concentrates or recombinant FVIII for greater than (>) 150 EDs.
- Participant is human immunodeficiency virus (HIV)-negative, or HIV-positive with stable disease and CD4+ count greater than or equal to (>=) 200 cells per cubic millimeter (/mm^3).
- Participant is hepatitis C virus (HCV) negative by antibody testing (if positive, additional polymerase chain reaction testing will be performed to confirm), as confirmed at screening; or HCV-positive with chronic stable hepatitis, as assessed by the investigator.
Exclusion Criteria:
- Participant has detectable FVIII inhibitory antibodies (>=0.6 Bethesda units [BU] per milliliter [/mL] using the Nijmegen modification of the Bethesda assay) as confirmed by the central laboratory at screening.
- Participant has a confirmed history of FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay or >=0.6 BU using the Bethesda assay) at any time prior to screening.
- Participant has a known hypersensitivity to Adynovate or ADVATE or any of the components of the study drugs, such as mouse or hamster proteins, or other FVIII products.
- Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (example, qualitative platelet defect or von Willebrand's disease).
- Participant has severe hepatic dysfunction (example, >=5 times the upper limit of normal [ULN] for alanine aminotransferase [ALT] or aspartate aminotransferase [AST], a recent or persistent international normalized ratio [INR] >1.5, as confirmed by the local laboratory at screening).
- Participant has severe renal impairment (serum creatinine >1.5 times the ULN) as confirmed by the local laboratory at screening.
- Participant is planned or likely to undergo major surgery during the study period.
- Participant has current or recent (<30 days) use of other PEGylated drugs before study participation or scheduled use of such drugs during study participation.
- Participant has received emicizumab therapy within 6 months of screening.
- Participant is currently receiving, or scheduled to receive during the study, an immunomodulating drug (example, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 milligram per day [mg/day], or alpha-interferon) other than antiretroviral chemotherapy.
- Participant has participated in another clinical study involving the use of an investigational product (IP) other than Adynovate or an investigational device within 30 days before the screening visit or is scheduled to participate in another clinical study involving an IP or investigational device during this study.
- Participant has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
- Participant, in the opinion of the investigator, is unable or unwilling to comply with the study protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Adynovate 45±5 IU/kg
Participants will receive prophylactic treatment with Adynovate (45 [±5] international units per kilogram [IU/kg]), infusion, intravenously, twice-weekly, over a period of 26 weeks or at least 50 EDs, whichever occurs last.
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Adynovate will be injected intravenously using an appropriately sized syringe as a bolus infusion over a period of less than or equal to (<=) 5 minutes (maximum infusion rate, 10 milliliters per minute [mL/min]).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Total Annualized Bleeding Rates (ABR)
Time Frame: Baseline up to Week 26
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Total ABR for all bleeding episodes, spontaneous or traumatic, recorded in the participant's electronic diary and/or recorded in the physician/nurse/study site notes will be reported.
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Baseline up to Week 26
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Adynovate Infusions per Week During the Prophylactic Treatment Period
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Number of Adynovate Infusions per Month During the Prophylactic Treatment Period
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Weight-adjusted Consumption of Adynovate per Week During the Prophylactic Treatment Period
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Weight-adjusted Consumption of Adynovate per Month During the Prophylactic Treatment Period
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Percentage of Participants With Zero Bleeding Episodes During the Study
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Time Intervals Between Bleeding Episodes
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Overall Hemostatic Efficacy Rating at Bleed Resolution for Treatment of Breakthrough Bleeding Episodes
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Number of Adynovate Infusions per Bleeding Episode
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Weight-adjusted Consumption of Adynovate per Bleeding Episode
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Number of Minor Surgeries With Hemostatic Efficacy Response Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator
Time Frame: Baseline up to Week 26
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GHEA score consists of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Peri-operative Efficacy Assessment Scale.
Each rating scale is based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None).
Total score ranged from 0 to 9, where scores evaluates as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2).
The scores of 3 individual ratings scales will be added together to form a GHEA score.
For a GHEA score of 7 to be rated "excellent" with no individual assessment scores less than (<) 2 and at least 1 assessment score equal to (=) 3; otherwise a score of 7 will be rated "good".
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Baseline up to Week 26
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Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator
Time Frame: Post-operative: Day 1 and at discharge Week 26
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Post-operative: Day 1 and at discharge Week 26
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Number of Participants who Require Perioperative Transfusion of Blood, Red blood Cells, Platelets, and Other Blood Products
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Screening up to Week 26
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TEAEs will include TEAEs by severity, TEAEs by causality, thromboembolic events, hypersensitivity reactions, any clinically significant changes in vital signs and clinical laboratory parameters.
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Screening up to Week 26
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Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein
Time Frame: Screening up to Week 26
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Screening up to Week 26
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FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Incremental Recovery Over Time During Adynovate Prophylactic Treatment
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Pre-dose Level of FVIII Activity and Antigen and von Willebrand Factor (VWF) Antigen in Plasma
Time Frame: Baseline up to Week 26: Within 30 minutes pre-infusion
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Baseline up to Week 26: Within 30 minutes pre-infusion
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ABR Based on Bleeding Site and Cause
Time Frame: Baseline up to Week 26
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Baseline up to Week 26
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Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Volume of Distribution (V) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: Within 30 minutes pre-infusion
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Baseline and Week 20: Within 30 minutes pre-infusion
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Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
Time Frame: Baseline and Week 20: 0-96 hours post-infusion
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Baseline and Week 20: 0-96 hours post-infusion
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, Takeda
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TAK-660-3001
- 2023-000502-26 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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