Clinical trial NCT05707351: A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A
Official title: 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%)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-01-31
Enrollment: 37
Sex: MALE
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: 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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Participant and/or legally authorized representative understands and is willing and able to comply with all requirements of the study protocol.
3. Participant should be ethnic Chinese.
4. Participant is 12 to 65 years of age at screening and male.
5. 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.
6. The last on-demand or prophylactic treatment received is within 3 months before screening.
7. Participant has documented previous treatment with plasma-derived FVIII concentrates or recombinant FVIII for greater than (\>) 150 EDs.
8. 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).
9. 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:

1. 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.
2. 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.
3. 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.
4. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (example, qualitative platelet defect or von Willebrand's disease).
5. 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).
6. Participant has severe renal impairment (serum creatinine \>1.5 times the ULN) as confirmed by the local laboratory at screening.
7. Participant is planned or likely to undergo major surgery during the study period.
8. Participant has current or recent (\<30 days) use of other PEGylated drugs before study participation or scheduled use of such drugs during study participation.
9. Participant has received emicizumab therapy within 6 months of screening.
10. 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.
11. 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.
12. 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.
13. Participant, in the opinion of the investigator, is unable or unwilling to comply with the study protocol.

Primary outcomes:
measure: Total Annualized Bleeding Rates (ABR)
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Secondary outcomes:
measure: ABR Based on Bleeding Site
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: ABR Based on Bleeding Cause
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Percentage of Participants With Zero Bleeding Episodes During the Study
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Average Time Interval Between Bleeding Episodes (BEs)
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Adynovate Infusions Per Bleeding Episode
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Weight-adjusted Consumption of Adynovate Per Bleeding Episode
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Minor Surgeries With Hemostatic Efficacy Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator
timeFrame: Post-operative: Day 1 and at discharge Week 26
measure: Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate
timeFrame: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs)
timeFrame: Up to approximately 28 weeks
measure: Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein
timeFrame: Up to approximately 28 weeks
measure: FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours
measure: Incremental Recovery Over Time During Adynovate Prophylactic Treatment
timeFrame: Baseline, Week 6, and Study Completion (approximately Week 28)
measure: Pre-dose Level of FVIII Activity in Plasma
timeFrame: Baseline, Weeks 2, 6, 12, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
measure: Pre-dose Level of FVIII Antigen in Plasma
timeFrame: Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
measure: Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma
timeFrame: Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion
measure: Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
measure: Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
measure: 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
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
measure: Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
measure: Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
measure: Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate
timeFrame: Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Children's Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical University
city: Hefei
country: China
facility: Anhui Province Hospital
city: Jinan
country: China
facility: Jinan Central Hospital
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: