A Study of Adynovate in Previously Treated Chinese Teenagers and Adults With Severe Hemophilia A

Hemophilia A Clinical Trial

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%)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05707351
• Other study ID #: TAK-660-3001
• Secondary ID: 2023-000502-26
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 27, 2023
• Est. completion date: October 8, 2024

Study information

• Verified date: April 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 37
• Est. completion date: October 8, 2024
• Est. primary completion date: October 8, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• Adynovate
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]).

Locations

Country	Name	City	State
China	Beijing Children's Hospital, Capital Medical University	Beijing
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing
China	Xiangya Hospital of Central South University	Changsha
China	Fujian Medical University Union Hospital	Fuzhou
China	Nanfang Hospital Southern Medical University	Guangzhou
China	Anhui Province Hospital	Hefei
China	Jinan Central Hospital	Jinan
China	Shenzhen Second People's Hospital	Shenzhen
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences	Tianjin
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Annualized Bleeding Rates (ABR)	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.	Baseline up to Week 26
Secondary	ABR Based on Bleeding Site and Cause		Baseline up to Week 26
Secondary	Number of Adynovate Infusions per Week During the Prophylactic Treatment Period		Baseline up to Week 26
Secondary	Number of Adynovate Infusions per Month During the Prophylactic Treatment Period		Baseline up to Week 26
Secondary	Weight-adjusted Consumption of Adynovate per Week During the Prophylactic Treatment Period		Baseline up to Week 26
Secondary	Weight-adjusted Consumption of Adynovate per Month During the Prophylactic Treatment Period		Baseline up to Week 26
Secondary	Percentage of Participants With Zero Bleeding Episodes During the Study		Baseline up to Week 26
Secondary	Time Intervals Between Bleeding Episodes		Baseline up to Week 26
Secondary	Overall Hemostatic Efficacy Rating at Bleed Resolution for Treatment of Breakthrough Bleeding Episodes		Baseline up to Week 26
Secondary	Number of Adynovate Infusions per Bleeding Episode		Baseline up to Week 26
Secondary	Weight-adjusted Consumption of Adynovate per Bleeding Episode		Baseline up to Week 26
Secondary	Number of Minor Surgeries With Hemostatic Efficacy Response Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator	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".	Baseline up to Week 26
Secondary	Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator		Post-operative: Day 1 and at discharge Week 26
Secondary	Number of Participants who Require Perioperative Transfusion of Blood, Red blood Cells, Platelets, and Other Blood Products		Baseline up to Week 26
Secondary	Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate		Baseline up to Week 26
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAEs will include TEAEs by severity, TEAEs by causality, thromboembolic events, hypersensitivity reactions, any clinically significant changes in vital signs and clinical laboratory parameters.	Screening up to Week 26
Secondary	Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein		Screening up to Week 26
Secondary	FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay		Baseline and Week 20: 0-96 hours post-infusion
Secondary	Incremental Recovery Over Time During Adynovate Prophylactic Treatment		Baseline up to Week 26
Secondary	Pre-dose Level of FVIII Activity and Antigen and von Willebrand Factor (VWF) Antigen in Plasma		Baseline up to Week 26: Within 30 minutes pre-infusion
Secondary	Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate		Baseline and Week 20: 0-96 hours post-infusion
Secondary	Volume of Distribution (V) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate		Baseline and Week 20: 0-96 hours post-infusion
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		Baseline and Week 20: 0-96 hours post-infusion
Secondary	Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate		Baseline and Week 20: 0-96 hours post-infusion
Secondary	Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate		Baseline and Week 20: Within 30 minutes pre-infusion
Secondary	Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate		Baseline and Week 20: 0-96 hours post-infusion

External Links

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