A Study of ADVATE in People With Hemophilia A in India

Hemophilia A Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04985682
• Other study ID #: TAK-761-4009
• Secondary ID: 2022-004149-11
• Status: Completed
• Phase: Phase 4
• Start date: January 14, 2022
• Est. completion date: February 10, 2023

Study information

• Verified date: August 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: February 10, 2023
• Est. primary completion date: February 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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 a-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.

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Biological:
• ADVATE
Antihemophilic factor (AHF) activity expressed in international units (IU) per vial.

Locations

Country	Name	City	State
India	St. John's Medical College	Bengaluru
India	Amrita Institute of Medical Science & Research Centre	Ernakulam	Kerala
India	K J Somaiya Hospital & Research Centre	Mumbai
India	All India Institute of Medical Sciences (AIIMS)	New Delhi
India	Unique Children's Hospital Pvt. Ltd.	Pune

Sponsors (2)

Lead Sponsor	Collaborator
Baxalta now part of Shire	Takeda Development Center Americas, Inc.

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline (Day 0) up to end of study (up to 12.9 months)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Total Number of ADVATE Infusions Required During Prophylactic Treatment		Baseline (Day 0) up to end of study (up to 12.9 months)
Secondary	Average Number of ADVATE Infusions Required Per Week During Prophylactic Treatment		Baseline (Day 0) up to end of study (up to 12.9 months)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of ADVATE Infusions Required to Achieve Resolution of Bleeding Episodes		Baseline (Day 0) up to end of study (up to 12.9 months)
Secondary	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)

External Links

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