A Study of ADVATE in People With Hemophilia A in India

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Hemophilia A

Intervention / Treatment
-----------------
* Biological: ADVATE


Participation Criteria
=================
Eligibility Criteria
-----------------
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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haemophilia A Group<br>Participants with hemophilia A will be treated with ADVATE according to a regimen determined by the study site treating physician study site and in accordance with the national product label under standard clinical practice. | Biological: ADVATE<br>* Antihemophilic factor (AHF) activity expressed in international units (IU) per vial.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAE) Least Possibly Related to ADVATE | A SAE is any untoward clinical manifestation of signs, symptoms or outcomes as life-threatening, requires inpatient hospitalization or result in death. Number of participants with SAEs ((including FVIII inhibitor formation) that are at least possibly related to ADVATE will be reported. | Baseline up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Non-serious Adverse Events (AEs) Least Possibly Related to ADVATE | Number of participants with non-serious AEs that are at least possibly related to ADVATE will be reported. | Baseline up to 6 months | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameter | Clinical laboratory parameter includes hematology, clinical chemistry, viral serology, FVIII antigen, FVIII activity, incremental recovery, and FVIII inhibitor. Changes in laboratory values may be considered as AE if they are judged to be clinically significant. | Baseline up to 6 months | 
| Annualized Bleeding Rate (ABR) With Prophylactic Treatment of ADVATE | The total ABR and ABR by bleed cause or sites (example, joint, non-joint, target joints, spontaneous, and traumatic) will be reported. | Baseline up to 6 months | 
| Total Number of ADVATE Infusions Required During Prophylactic Treatment of Bleeding Episode | The total number of ADVATE infusions required during prophylactic treatment of bleeding episode will be reported. | Baseline up to 6 months | 
| Average Number of ADVATE Infusions Required During Prophylactic Treatment of Bleeding Episode | The average number (per week and per month) of ADVATE infusions required during prophylactic treatment of bleeding episode will be reported. | Baseline up to 6 months | 
| Total Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment of Bleeding Episode | The total body mass adjusted consumption of ADVATE during prophylactic treatment will be reported. | Baseline up to 6 months | 
| Average Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment of Bleeding Episode | The average body mass adjusted consumption of ADVATE per week and per month during prophylactic treatment will be reported. | Baseline up to 6 months | 
| Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes | The overall hemostatic efficacy rating of ADVATE for resolution of bleeding episodes will be reported. | Baseline up to 6 months | 
| Number of ADVATE Infusions Required to Achieve Resolution of Bleeding Episodes | The number of infusions of ADVATE required to control a bleeding episode will be reported. | Baseline up to 6 months | 
| Total Body Mass Adjusted Consumption of ADVATE per Bleeding Episode | The body mass adjusted consumption of ADVATE per bleeding event will be reported. | Baseline up to 6 months |