Trial Outcomes & Findings for Study of TAK-672 in Participants With Acquired Hemophilia A (NCT NCT04580407)

Results Overview

Percentage of severe bleeding episodes with demonstrated response to TAK-672 therapy at 24 hours after the initiation of treatment was assessed by using a well-defined 4-point ordinal scale - A 'positive response' was defined as 'effective' (bleeding stopped with clinical control and FVIII:C levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII:C levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' was defined as 'bleeding slightly reduced or unchanged and FVIII:C levels of less than 50%'. 'Not effective' was defined as 'bleeding worsening and FVIII:C levels of less than 20%'.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

5 participants

Primary outcome timeframe

24 hours after the initial dose of TAK-672

Results posted on

2024-12-02

Participant Flow

Participants took part in the study at 9 investigative sites in Japan from 09 April 2021 to 29 November 2022.

A total of 5 participants with Acquired Hemophilia A (AHA) were enrolled in this study to receive TAK-672 at an initial dose of 200 units per kilogram (U/kg).

Participant milestones

Participant milestones
Measure	TAK-672 TAK-672 was administered at an initial dose of 200 U/kg with intravenous (IV) infusion at a rate of 1-2 milliliters per minute (mL/min) at Day 1. Subsequent doses were determined based on the post-infusion factor VIII activity (FVIII:C) achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	TAK-672 TAK-672 was administered at an initial dose of 200 U/kg with intravenous (IV) infusion at a rate of 1-2 milliliters per minute (mL/min) at Day 1. Subsequent doses were determined based on the post-infusion factor VIII activity (FVIII:C) achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Overall Study Judged to be Required to Receive Prophylactic Treatment with Emicizumab	1

Baseline Characteristics

Study of TAK-672 in Participants With Acquired Hemophilia A

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Age, Continuous	76.0 years STANDARD_DEVIATION 10.02 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 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	5 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
Height	154.1 centimeters (cm) STANDARD_DEVIATION 12.71 • n=5 Participants
Weight	53.42 kilograms (kg) STANDARD_DEVIATION 7.529 • n=5 Participants

PRIMARY outcome

Timeframe: 24 hours after the initial dose of TAK-672

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Percentage of severe bleeding episodes with demonstrated response to TAK-672 therapy at 24 hours after the initiation of treatment was assessed by using a well-defined 4-point ordinal scale - A 'positive response' was defined as 'effective' (bleeding stopped with clinical control and FVIII:C levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII:C levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' was defined as 'bleeding slightly reduced or unchanged and FVIII:C levels of less than 50%'. 'Not effective' was defined as 'bleeding worsening and FVIII:C levels of less than 20%'.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Percentage of Participants With Severe Bleeding Episodes Who Demonstrated Response to TAK-672 Therapy at 24 Hours After the Initiation of Treatment	100 percentage of participants Interval 47.818 to 100.0

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

If the status assessed by the investigator at the end of study treatment of initial treatment period was "successfully controlled", the participant's initial severe bleeding episode was considered as successfully controlled.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Percentage of Participants With Severe Bleeding Episodes Successfully Controlled With TAK-672 Therapy, as Assessed by the Investigator	100 percentage of participants Interval 47.818 to 100.0

SECONDARY outcome

Timeframe: At 0.5, 8, 16, 24, 48, 60, 96, and 120 hours post dose and at 1, 14, 28, 42, 56, 70, and 90 day follow-up

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses. Number of participants analyzed are the number of participants available for analysis at the given timepoint.

A 'positive response' was defined as 'effective' (bleeding stopped with clinical control and FVIII:C levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII:C levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' was defined as 'bleeding slightly reduced or unchanged and FVIII:C levels of less than 50%'. 'Not effective' was defined as 'bleeding worsening and FVIII:C levels of less than 20%'. Data is reported only for the timepoints having at least one participant available for analysis.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 0.5 Hours	80.0 percentage of participants Interval 28.358 to 99.495
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 8 Hours	100 percentage of participants Interval 47.818 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 16 Hours	100 percentage of participants Interval 39.764 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 24 Hours	100 percentage of participants Interval 47.818 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 48 Hours	100 percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 60 Hours	100 percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 96 Hours	100 percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period at 120 Hours	100 percentage of participants Interval 2.5 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 24 Hours on Day 1	100 percentage of participants Interval 47.818 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 14 Days	100 percentage of participants Interval 47.818 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 28 Days	100 percentage of participants Interval 39.764 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 42 Days	100 percentage of participants Interval 39.764 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 56 Days	100 percentage of participants Interval 39.764 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 70 Days	100 percentage of participants Interval 39.764 to 100.0
Percentage of Participants With Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator Initial Treatment Period Follow-up at 90 Days (End of Study)	100 percentage of participants Interval 39.764 to 100.0

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

'Frequency of infusions ' was calculated as the 'average number of infusions per day'. 'Qualifying bleeding episode' was defined as the 'initial, severe bleeding episode'.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Frequency of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes	1.8 infusions per participant Standard Deviation 1.12

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

'Qualifying bleeding episode' was defined as the 'initial, severe bleeding episode'. Total dose of infusions is sum of doses from start of treatment with TAK-672 for qualifying bleeding episodes until completion of the management of the bleeding.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Total Dose of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes	38640.0 dose per participant Standard Deviation 28442.45

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

'Qualifying bleeding episode' was defined as the 'initial, severe bleeding episode'. If the status assessed by the investigator at the end of study treatment of initial treatment period was "successfully controlled", the participant's initial severe bleeding episode was considered as successfully controlled.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Total Number of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes	2.6 infusions per participant Standard Deviation 0.89

SECONDARY outcome

Timeframe: At 0.5, 8, 16, 24, 48, 60, 96,120, and 144 hours post dose and at 1, 14, 28, 42, 56, 70, and 90 day follow-up

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses. Number of participants analyzed are the number of participants available for analysis at the given timepoint.

Percentage of participants with response to TAK-672 therapy at specified time points and eventual control of severe bleeding episodes was assessed to determine the correlation between response to TAK-672 therapy and eventual control of severe bleeding episodes. A 'positive response' was defined as 'effective' (bleeding stopped with clinical control and FVIII:C levels of 50% or higher) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII:C levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' was defined as 'bleeding slightly reduced or unchanged and FVIII:C levels of less than 50%'. 'Not effective' was defined as 'bleeding worsening and FVIII:C levels of less than 20%'. Data is reported only for the timepoints having at least one participant available for analysis.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 24 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 0.5 Hours	80.0 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 8 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 16 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 48 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 60 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 96 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 120 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period at 144 Hours	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 24 Hours on Day 1	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 14 Days	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 28 Days	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 42 Days	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 56 Days	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 70 Days	100 percentage of participants
Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes Initial Treatment Period Follow-up at 90 days (End of Study)	100 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Mean value of pre-infusion anti-TAK-672 antibody titers (unit: Bethesda unit per milliliters \[BU/mL\]) in participants with successful control of the bleeding episode was reported as a result of correlation among the pre-infusion pFVIII inhibitor titers and the eventual control of the bleeding episode in this outcome measure.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Mean Value of Pre-infusion Anti-TAK-672 Antibody Titers in Participants With Successful Control of the Bleeding Episode	3.78 Bethesda unit per milliliters (BU/mL) Standard Deviation 4.784

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Mean value of total dose per participant for initial treatment period (unit: units/kg per participant) in participants with successful control of the bleeding episode was reported as a results of correlation among the total dose per participant of TAK-672 and the eventual control of the bleeding episode in this outcome measure.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Mean Value of Total Dose Per Participant in Participants With Successful Control of the Bleeding Episode	38640.0 units/kg per participant Standard Deviation 28442.45

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Number of participants with positive response at 24 hours after the initiation of treatment in participants with successful control of the bleeding episode was reported as a results of correlation among the response at 24 hours and the eventual control of the bleeding episode. A 'positive response' was defined as 'effective'(bleeding stopped with clinical control and FVIII:C levels of 50%or higher) or 'partially effective'(bleeding reduced with clinical stabilization and FVIII:C levels of 20%or higher) control of bleeding, as determined by investigator using 4-point rating scale (effective-partially effective-poorly effective-not effective).

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Number of Participants With Positive Response at 24 Hours After the Initiation of Treatment in Participants With Successful Control of the Bleeding Episode	5 Participants

SECONDARY outcome

Timeframe: Baseline, 72 hours postdose, and at 14, 28, 42, 56, 70, and 90 days follow-up

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses. Number analyzed is the number of participants available for analysis at the given timepoint.

Data is reported only for the timepoints having at least one participant available for analysis.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Anti-hFVIII Inhibitor Titers Initial Treatment Period Baseline	57.6 BU/mL Standard Deviation 55.24
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 70 Days	53.8 BU/mL Standard Deviation 107.50
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 90 Days (End of Study)	52.0 BU/mL Standard Deviation 104.00
Anti-hFVIII Inhibitor Titers Initial Treatment Period at 72 Hours	60.0 BU/mL Standard Deviation NA Standard Deviation (SD) was not estimable for 1 participant.
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 14 Days	35.0 BU/mL Standard Deviation 65.51
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 28 Days	27.3 BU/mL Standard Deviation 51.84
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 42 Days	44.0 BU/mL Standard Deviation 88.00
Anti-hFVIII Inhibitor Titers Initial Treatment Period Follow-up at 56 Days	46.3 BU/mL Standard Deviation 92.50

SECONDARY outcome

Timeframe: Baseline, 72 hours postdose, and at 14, 28, 42, 56, 70, and 90 days follow-up

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses. Number analyzed is the number of participants available for analysis at the given timepoint.

Data is reported only for the timepoints having at least one participant available for analysis.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Anti-pFVIII Inhibitor Titer Initial Treatment Period at Baseline	3.78 BU/mL Standard Deviation 4.784
Anti-pFVIII Inhibitor Titer Initial Treatment Period at 72 Hours	0.00 BU/mL Standard Deviation NA SD was not estimable for 1 participant.
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 14 Days	1.34 BU/mL Standard Deviation 2.475
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 28 Days	1.18 BU/mL Standard Deviation 2.350
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 42 Days	2.23 BU/mL Standard Deviation 4.450
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 56 Days	3.33 BU/mL Standard Deviation 6.650
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 70 Days	3.68 BU/mL Standard Deviation 7.350
Anti-pFVIII Inhibitor Titer Initial Treatment Period Follow-up at 90 Days (End of Study)	3.13 BU/mL Standard Deviation 6.250

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Total dose is sum of doses from start of treatment with TAK-672 until completion of hemostasis control.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Total Dose Per Participant From Initial Dose of TAK-672 Until Completion of Hemostasis Control	38640.0 dose per participant Standard Deviation 28442.45

SECONDARY outcome

Timeframe: From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum)

Population: FAS included all participants who had received at least 1 dose of the TAK-672 and was used for the efficacy analyses.

Outcome measures

Outcome measures
Measure	TAK-672 n=5 Participants TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Number of Participants With New Qualified Severe Bleeding Episodes	1 Participants

Adverse Events

TAK-672

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TAK-672 n=5 participants at risk TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Endocrine disorders Central hypothyroidism	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Cryoglobulinaemia	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Haemorrhagic diathesis	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	TAK-672 n=5 participants at risk TAK-672 was administered at an initial dose of 200 U/kg with IV infusion at a rate of 1-2 mL/min at Day 1. Subsequent doses were determined based on the post-infusion FVIII:C achieved after the most recent dose given, the target FVIII:C, and pFVIII inhibitor titer.
Gastrointestinal disorders Anal fissure	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Apnoea	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood urine present	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Conjunctival haemorrhage	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Decubitus ulcer	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Delirium	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Erythema	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Haematochezia	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	60.0% 3/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hyperplastic cholecystopathy	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hypoaesthesia	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Mouth haemorrhage	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Nephrolithiasis	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Periodontal disease	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Psoriasis	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary alveolar haemorrhage	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Skin abrasion	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Skin haemorrhage	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Vessel puncture site haemorrhage	20.0% 1/5 • From first dose of study drug up to 90 days after the last dose of study drug or until discontinued (Up to 95 days as a maximum) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Study

Director

Phone: +1-877-825-3327

Email: [email protected]

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