Phase 3
N=37
A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A
Hemophilia A
Bottom Line
View on ClinicalTrials.gov: NCT05707351 ↗Enrolled (actual)
37
Serious AEs
2.7%
Results posted
May 2025
Primary outcome: Primary: Total Annualized Bleeding Rates (ABR) — 4.1 bleeds per year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Adynovate (Biological)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- Male
- Sponsor
- Takeda
- Primary completion
- Sep 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Total Annualized Bleeding Rates (ABR) |
4.1 | — |
| SECONDARY ABR Based on Bleeding Site |
2.7; 1.4 | — |
| SECONDARY ABR Based on Bleeding Cause |
3.8; 0.3 | — |
| SECONDARY Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period |
2.003 | — |
| SECONDARY Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period |
8.711 | — |
| SECONDARY Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period |
89.637 | — |
| SECONDARY Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period |
389.760 | — |
| SECONDARY Percentage of Participants With Zero Bleeding Episodes During the Study |
54.1 | — |
| SECONDARY Average Time Interval Between Bleeding Episodes (BEs) |
61.869 | — |
| SECONDARY Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode |
7; 14; 4; 0; 6 | — |
| SECONDARY Number of Adynovate Infusions Per Bleeding Episode |
2.839 | — |
| SECONDARY Weight-adjusted Consumption of Adynovate Per Bleeding Episode |
77.766 | — |
| SECONDARY Number of Minor Surgeries With Hemostatic Efficacy Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator |
— | — |
| SECONDARY Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator |
— | — |
| SECONDARY Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products |
— | — |
| SECONDARY Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate |
— | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs) |
16; 1 | — |
| SECONDARY 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 |
0; 0; 0; 0 | — |
| SECONDARY FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay |
0.00; 112.02; 106.67; 94.64; 87.67; 71.87 | — |
| SECONDARY Incremental Recovery Over Time During Adynovate Prophylactic Treatment |
2.4777; 2.5147; 2.4083 | — |
| SECONDARY Pre-dose Level of FVIII Activity in Plasma |
0.06; 3.28; 2.91; 3.61; 7.06 | — |
| SECONDARY Pre-dose Level of FVIII Antigen in Plasma |
0.0276; 0.0782; 0.0689; 0.0649; 0.0856; 0.1011 | — |
| SECONDARY Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma |
83.69; 84.46; 84.99; 86.57; 91.26; 90.26 | — |
| SECONDARY Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate |
0.0206; 0.0192 | — |
| SECONDARY Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate |
0.458; 0.480 | — |
| SECONDARY 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 |
2348; 2582 | — |
| SECONDARY Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate |
113; 115 | — |
| SECONDARY Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate |
0; 0 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate |
16.0; 18.5 | — |
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
- 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 ( ) 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 ( 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.
Data sourced from ClinicalTrials.gov (NCT05707351). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.