A Study of ADVATE in People With Hemophilia A in India

Phase 4, Multicenter, Prospective, Interventional, Post-Marketing Study in Hemophilia A Patients in India Receiving ADVATE as On-Demand or Prophylaxis Under Standard Clinical Practice

The main aim of this study is to learn more about side effects of Advate when given as standard treatment to people with hemophilia A who have already been treated.

The study sponsor will not be involved in how participants are treated but will provide instructions on how the clinics will record what happens during the study. Participants will need to visit the study doctor 5 times in total during the study. During these visits, study data will be collected by the study doctor.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Biological: ADVATE

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Bengaluru, India, 560034
    • St. John's Medical College
  • Mumbai, India, 400022
    • K J Somaiya Hospital & Research Centre
  • New Delhi, India, 110029
    • All India Institute Of Medical Sciences (AIIMS)
  • Pune, India, 411019
    • Unique Children's Hospital Pvt. Ltd.
  • Kerala
    • Ernakulam, Kerala, India, 682041
      • Amrita Institute of Medical Science & Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The participant or legally authorized representative (in case of study participants less than (<) 18 years of age) gave written informed consent to participate in the study.
• Participant of any age with hemophilia A.

• Participant defined as a previously treated patient (PTP):

  • Participant aged greater than or equal to (>=) 6 years that has been previously treated with plasma-derived and/or recombinant FVIII concentrate(s) for a minimum of 150 exposure doses (EDs).
  • Participant aged less than <6 years that has been previously treated with plasma-derived or recombinant FVIII concentrate(s) for a minimum of 50 EDs.
• Participant as negative history of FVIII inhibitors and negative inhibitor at screening defined as less than 0.6 Bethesda units (BU) per milliliter (Nijmegen-modified Bethesda assay).
• Participant is human immunodeficiency virus negative (HIV-); or human immunodeficiency virus positive (HIV+) with stable disease and cluster of differentiation 4 (CD4+) count >=200 cells per cubic millimeter (mm^3), as confirmed by central laboratory at screening.
• Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, anti-body titer will be confirmed by PCR), as confirmed by central laboratory at screening; or hepatitis C virus positive (HCV+) with chronic stable hepatitis.
• Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

• Participant has known hypersensitivity to mouse or hamster proteins or to any of the excipients of FVIII (factor VIII) concentrates.
• Participant has been diagnosed with bleeding disorder(s) other than congenital hemophilia A, such as acquired hemophilia A, von Willebrand´s disease (VWD) or thrombocytopenia (platelet count <100,000 per milliliter).
• Participant has received treatment for hemophilia A with non-FVIII products or concentrates (example, emicizumab [Hemlibra®]) in the 6 months prior to screening.
• Participant has severe chronic hepatic dysfunction (example, >=5 times upper limit of normal alanine aminotransferase [ALT], aspartate aminotransferase [AST] or international normalized ratio [INR] >1.5 as confirmed by central laboratory at screening).
• Participant has planned or is likely to have, surgery during the study period.
• Participant has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug or alcohol use that, in the opinion of the investigator, would affect participant's safety or compliance.
• Participant currently receiving or is scheduled to receive during the course of the study, an immunomodulating drug (example, corticosteroid agents at a dose equivalent to hydrocortisone >10 milligram per day, or α-interferon) other than antiretroviral chemotherapy.
• Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
• Participant is a family member or employee of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemophilia A Group; Participants with hemophilia A were treated with ADVATE according to a regimen determined by the treating physician at the study site and in accordance with the national product label under standard clinical practice for 6.7 months.	Biological: ADVATE; Antihemophilic factor (AHF) activity expressed in international units (IU) per vial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAE) at Least Possibly Related to ADVATE	An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. An SAE was defined as any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of present hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or was a medically important event. Number of participants with SAEs (including FVIII inhibitor formation) that were at least possibly related to ADVATE were reported.	Baseline (Day 0) up to end of study (up to 12.9 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-serious Adverse Events (AEs) at Least Possibly Related to ADVATE	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product or medicinal product. Number of participants with non-serious AEs that were at least possibly related to ADVATE were reported.	Baseline (Day 0) up to end of study (up to 12.9 months)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	Clinical laboratory parameters included hematology, clinical chemistry, viral serology, factor VIII (FVIII) antigen, FVIII activity, incremental recovery, and FVIII inhibitor. Clinical significance was judged as per Investigator's assessment.	Baseline (Day 0) up to end of study (up to 12.9 months)
Total Annualized Bleeding Rate (ABR) With Prophylactic Treatment of ADVATE	ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error was estimated using a generalized linear model (GLM). The total ABR is reported in this outcome measure.	Baseline (Day 0) up to end of study (up to 12.9 months)
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed	ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error were estimated using a GLM. The ABR by bleed sites (example, joint, soft tissue, muscle, other [mouth, gums or nose] are reported in this outcome measure.	Baseline (Day 0) up to end of study (up to 12.9 months)
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed	ABR was defined as number of bleeding episodes during the study period divided by total number of study period days multiplied by 365.25. The mean ABR and standard error were estimated using a GLM. The ABR by bleed cause (example, spontaneous, injury, and unknown) are reported in this outcome measure.	Baseline (Day 0) up to end of study (up to 12.9 months)
Total Number of ADVATE Infusions Required During Prophylactic Treatment		Baseline (Day 0) up to end of study (up to 12.9 months)
Average Number of ADVATE Infusions Required Per Week During Prophylactic Treatment		Baseline (Day 0) up to end of study (up to 12.9 months)
Average Number of ADVATE Infusions Required Per Month During Prophylactic Treatment of Bleeding Episode		Baseline (Day 0) up to end of study (up to 12.9 months)
Total Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment	Body mass adjusted consumption international units per kilograms (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.	Baseline (Day 0) up to end of study (up to 12.9 months)
Average Body Mass Adjusted Consumption of ADVATE Per Week During Prophylactic Treatment	Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.	Baseline (Day 0) up to end of study (up to 12.9 months)
Average Body Mass Adjusted Consumption of ADVATE Per Month During Prophylactic Treatment	Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.	Baseline (Day 0) up to end of study (up to 12.9 months)
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes	Overall hemostatic efficacy for treatment of bleeding episodes was rated on 4-point Likert scale as: excellent=full relief of pain and cessation of objective signs of bleeding after a single infusion, no additional infusion is required for the control of bleeding and administration of further infusion to maintain hemostasis would not affect the scoring; good=definite pain relief and/or improvement in signs of bleeding after a single infusion, possibly requires more than 2 infusions for complete resolution and administration of further infusion to maintain hemostasis would not affect the scoring; moderate=probable and/or slight relief of pain and slight improvement in signs of bleeding after a single infusion, required multiple infusions for complete resolution; none=no improvement of signs or symptoms or conditions worsen.	Baseline (Day 0) up to end of study (up to 12.9 months)
Number of ADVATE Infusions Required to Achieve Resolution of Bleeding Episodes		Baseline (Day 0) up to end of study (up to 12.9 months)
Total Body Mass Adjusted Consumption of ADVATE Per Bleeding Episode	Body mass adjusted consumption (IU/kg) was derived as the total units infused (IU) divided by the last available body weight (kg) prior to the infusion.	Baseline (Day 0) up to end of study (up to 12.9 months)

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire
• Collaborators: Takeda Development Center Americas, Inc.
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Actual): February 10, 2023
• Study Completion (Actual): February 10, 2023

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: TAK-761-4009; 2022-004149-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No