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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04985682

Enrollment

Registered

2021-08-02

Start date

2022-01-14

Completion date

2023-02-10

Last updated

2024-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hemophilia A

Keywords

Drug Therapy

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.

Interventions

BIOLOGICALADVATE

Antihemophilic factor (AHF) activity expressed in international units (IU) per vial.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Serious Adverse Events (SAE) at Least Possibly Related to ADVATE	Baseline (Day 0) up to end of study (up to 12.9 months)	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.

Secondary

Measure	Time frame	Description
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
Total Annualized Bleeding Rate (ABR) With Prophylactic Treatment of ADVATE	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
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)	—
Number of Participants With Non-serious Adverse Events (AEs) at Least Possibly Related to ADVATE	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
Total Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
Average Body Mass Adjusted Consumption of ADVATE Per Week During Prophylactic Treatment	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
Average Body Mass Adjusted Consumption of ADVATE Per Month During Prophylactic Treatment	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
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	Baseline (Day 0) up to end of study (up to 12.9 months)	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.
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)	—

Countries

India

Participant flow

Recruitment details

Participants took part in the study at 4 investigative sites in India from 14 January 2022 to 10 February 2023.

Pre-assignment details

Participants previously treated for hemophilia A who met eligibility criteria were enrolled to receive ADVATE according to a dosing regimen determined by the treating physician and in accordance with the national product label.

Participants by arm

Arm	Count
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.	50
Total	50

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Hemophilia A Group
Age, Continuous	19.5 years STANDARD_DEVIATION 13.01
Body Mass Index (BMI)	19.9 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.42
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	152.0 centimeters (cm) STANDARD_DEVIATION 22.68
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	50 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Region of Enrollment India	50 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	50 Participants
Weight	48.5 kilograms (kg) STANDARD_DEVIATION 20.95

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 50
other Total, other adverse events	6 / 50
serious Total, serious adverse events	0 / 50

Outcome results

Primary

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.