Trial Outcomes & Findings for A Study of ADVATE in People With Hemophilia A in India (NCT NCT04985682)

NCT ID: NCT04985682

Last Updated: 2024-03-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 50 participants
• Primary outcome timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)
• Results posted on: 2024-03-07

Participant Flow

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

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.

Participant milestones

Measure	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.
Overall Study STARTED	50
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	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.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study of ADVATE in People With Hemophilia A in India

Baseline characteristics by cohort

Measure	Hemophilia A Group n=50 Participants 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.
Age, Continuous	19.5 years STANDARD_DEVIATION 13.01 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	50 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment India	50 Participants n=5 Participants
Weight	48.5 kilograms (kg) STANDARD_DEVIATION 20.95 • n=5 Participants
Height	152.0 centimeters (cm) STANDARD_DEVIATION 22.68 • n=5 Participants
Body Mass Index (BMI)	19.9 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.42 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: Safety Analysis Set (SAS) included all participants who received ADVATE at any time during the study.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Number of Participants With Serious Adverse Events (SAE) at Least Possibly Related to ADVATE	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: SAS included all participants who received ADVATE at any time during the study.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Number of Participants With Non-serious Adverse Events (AEs) at Least Possibly Related to ADVATE	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: SAS included all participants who received ADVATE at any time during the study.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Total Annualized Bleeding Rate (ABR) With Prophylactic Treatment of ADVATE	2.65 bleeds per year Standard Error 0.195

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed Bleed Location: Joint	2.33 bleeds per year Standard Error 0.203
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed Bleed Location: Soft Tissue	0.04 bleeds per year Standard Error 1.000
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed Bleed Location: Muscle	0.16 bleeds per year Standard Error 0.628
ABR With Prophylactic Treatment of ADVATE Categorized Based on Location of Bleed Bleed Location: Other (Mouth, Gums or Nose)	0.12 bleeds per year Standard Error 0.813

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed Bleed Type: Injury	0.20 bleeds per year Standard Error 0.692
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed Bleed Type: Spontaneous	1.86 bleeds per year Standard Error 0.211
ABR With Prophylactic Treatment of ADVATE Categorized Based on Type of Bleed Bleed Type: Unknown	0.59 bleeds per year Standard Error 0.541

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Total Number of ADVATE Infusions Required During Prophylactic Treatment	65.8 infusions Standard Deviation 22.92

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Average Number of ADVATE Infusions Required Per Week During Prophylactic Treatment	2.5 infusions per week Standard Deviation 0.87

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Average Number of ADVATE Infusions Required Per Month During Prophylactic Treatment of Bleeding Episode	11.0 infusions per month Standard Deviation 3.76

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Total Body Mass Adjusted Consumption of ADVATE During Prophylactic Treatment	1739.7 IU/kg Standard Deviation 621.18

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Average Body Mass Adjusted Consumption of ADVATE Per Week During Prophylactic Treatment	67.1 IU/kg per week Standard Deviation 24.12

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met.

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.

Outcome measures

Measure	Hemophilia A Group n=50 Participants 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.
Average Body Mass Adjusted Consumption of ADVATE Per Month During Prophylactic Treatment	291.7 IU/kg per month Standard Deviation 104.80

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Overall number of participants analyzed are the number of participants with bleeds who required ADVATE infusion for management of the bleeding episode.

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.

Outcome measures

Measure	Hemophilia A Group n=51 Treated Bleeds 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.
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes Excellent	21 bleeding episodes
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes Good	26 bleeding episodes
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes Moderate	4 bleeding episodes
Overall Hemostatic Efficacy Rating of ADVATE for Treatment of Bleeding Episodes None	0 bleeding episodes

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Overall number of participants analyzed are the number of participants with bleeds who required ADVATE infusion for management of the bleeding episode.

Outcome measures

Measure	Hemophilia A Group n=24 Participants 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.
Number of ADVATE Infusions Required to Achieve Resolution of Bleeding Episodes	1.2 infusions Standard Deviation 0.46

SECONDARY outcome

Timeframe: Baseline (Day 0) up to end of study (up to 12.9 months)

Population: EFAS comprised of all participants for whom all inclusion and none of the exclusion criteria were met. Overall number of participants analyzed are the number of participants with bleeds who required ADVATE infusion for management of the 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.

Outcome measures

Measure	Hemophilia A Group n=24 Participants 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.
Total Body Mass Adjusted Consumption of ADVATE Per Bleeding Episode	34.8 IU/kg Standard Deviation 19.79

Adverse Events

Hemophilia A Group

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Hemophilia A Group n=50 participants at risk 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.
General disorders Pyrexia	4.0% 2/50 • Number of events 2 • Baseline (Day 0) up to end of study (up to 12.9 months) SAS included all participants who received ADVATE at any time during the study.
Infections and infestations Varicella	2.0% 1/50 • Number of events 1 • Baseline (Day 0) up to end of study (up to 12.9 months) SAS included all participants who received ADVATE at any time during the study.
Injury, poisoning and procedural complications Animal bite	2.0% 1/50 • Number of events 1 • Baseline (Day 0) up to end of study (up to 12.9 months) SAS included all participants who received ADVATE at any time during the study.
Injury, poisoning and procedural complications Joint injury	2.0% 1/50 • Number of events 3 • Baseline (Day 0) up to end of study (up to 12.9 months) SAS included all participants who received ADVATE at any time during the study.
Injury, poisoning and procedural complications Skin laceration	4.0% 2/50 • Number of events 2 • Baseline (Day 0) up to end of study (up to 12.9 months) SAS included all participants who received ADVATE at any time during the study.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: TrialDisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER