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Acquired Hemophilia APhase 2/3NCT04580407

Study of TAK-672 in Participants With Acquired Hemophilia A

A Phase 2/3 study testing TAK-672 in people with Acquired Hemophilia A, run by Takeda at 9 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The main aims of the study are to learn if TAK-672 can control bleeds in participants with acquired hemophilia A and if the participants have side effects from TAK-672. Acquired hemophilia A is when people's immune system attacks specific proteins, known as clotting factors, in their bodies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acquired Hemophilia A
What is being tested?
TAK-672
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
9 sitesJapan
Study dates
9 Apr 2021to 29 Nov 2022
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female Japanese participants of >=18 years of age.
  • Participants who (or their legally authorized representatives) have provided his/her written informed consent form prior to any study-related procedures and study product administration.
  • Participants with a diagnosis of AHA based on clinical evaluation and supportive local laboratory testing as shown below:
  • Presentation with spontaneous bleeding without anatomical cause and without prior known bleeding disorder.
  • Prolonged activated partial thromboplastin time (aPTT) without explanation.
  • Abnormal aPTT cross mixing test consistent with FVIII inhibitors
Show all 18Show fewer
  • Confirmation of a low FVIII:C.
  • Positive FVIII inhibitor (>=0.6 BU) as measured either in the local or central laboratory
  • Participants with a severe bleeding episode which the investigator finds necessary to treat and whose severe bleeding episode meets at least 1 of the following criteria:
  • Bleeds that pose a threat to a vital organ that could threaten life (e.g. intracranial bleed, or any site that could obstruct the airway).
  • Bleeds that pose a threat to a vital organ where life is not threatened but the organ function could be impaired (e.g., intraspinal bleed threatening the spinal cord and/or nerve conduction; a continual bleed into the kidney or bladder that could result in an obstructive uropathy, testicular bleed, bleed in and around the eye).
  • Bleeds requiring a blood transfusion to maintain the Hgb level at above-life or organ threatening levels (e.g. post-surgical, gastro-intestinal, retro-peritoneal, and thigh bleeds).
  • Intramuscular bleeds where muscle viability and/or neurovascular integrity is significantly compromised or at risk of being compromised.
  • Intra-articular bleeds impacting a major joint associated with severe pain, swelling and severe loss of joint mobility (reduced >70%) or where a bleed could result in joint destruction (e.g. in and around the femoral head).
  • Participants who are taking anti-thrombotics (including anti-platelet agents and anticoagulantswith confirmatory laboratory testing documenting specific FVIII inhibitor titer and with 3 half-lives of the agent have elapsed since the last dose.
  • Participants with expected life expectancies of at least 90 days prior to the onset of the hemorrhagic episode.
  • Participants of reproductive age who have agreed to use acceptable methods of contraception and if female, undergo pregnancy testing as part of the screening process.
  • Participant who are able to willing and able to comply with the requirements of the protocol.

Who cannot join

  • Participants with an established reason for bleeding that is not correctable even with hemostatic therapy.
  • Participants presenting a bleeding episode that is assessed likely to resolve on its own, even if left untreated.
  • Participants with a known major sensitivity (anaphylactoid reactions) to therapeutic products of porcine or hamster origin; examples include therapeutics of porcine origin (e.g. previously marketed porcine FVIII, Hyate: C) and recombinant therapeutics prepared from hamster cells (e.g. Humira, Advate, and Enbrel).
  • Participants with the use of hemophilia medication: prior to the administration of TAK-672 under one of the following conditions: (1) use of "recombinant activated factor VII (rFVI)Ia " within 3 hours prior to TAK-672 administration (2) use of " activated prothrombin complex concentrate (aPCC)" within 6 hours prior to TAK-672 administration or (3) use of " plasma-derived FX/FVIIa complex concentrate (pd-FX/FVIIa) " within 8 hours prior to TAK-672 administration.
  • Participants with an anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of TAK-672, or whose safety or efficacy may be affected by TAK-672.
  • Participants who are currently pregnant or breastfeeding, or planning to become pregnant or father a child during the study
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  • Participants who have participated in another clinical study and has been exposed to an investigational product or device within 30 days prior to the study enrollment.
  • Participants who are scheduled to participate in another non-observational (interventional) clinical study involving an investigational product or device during the course of the study.
  • Participants who are unable to or unwilling to comply with the study design, protocol requirements, and/or the follow-up procedures.
  • Participants whose majority of age are under legal protection.
  • Participants who are an immediate family member, study site employee, or are in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g. spouse, parent, child, sibling) or may consent under duress.
  • Participants who are judged by the investigator as being ineligible for any other reason.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Japan9 sites
  • Nagoya University Hospital

    Aichi, Nagoya

  • Chiba University Hospital

    Chiba

  • Fukushima Medical University Hospital

    Fukushima

  • Nara Medical University Hospital

    Kashihara-shi, Nara

  • Gunma University Hospital

    Maebashi, Gunma

  • Uonuma Kikan Hospital

    Minamiuonuma, Niigata

  • Tokyo Saiseikai Central Hospital

    Mita, Tokyo

  • Jichi Medical University Hospital

    Shimotsuke, Tochigi

  • Yamagata University Hospital

    Yamagata

Other trials in Japan

About this study

Official title: A Phase 2/3, Open-Label, Non-controlled Study to Evaluate the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (rpFVIII, TAK-672), in the Treatment of Serious Bleeding Episode in Japanese Subjects With Acquired Hemophilia A (AHA)

The main aims of the study are to learn if TAK-672 can control bleeds in participants with acquired hemophilia A and if the participants have side effects from TAK-672. Acquired hemophilia A is when people's immune system attacks specific proteins, known as clotting factors, in their bodies. This is different from hemophilia A, which is a condition people are born with.

At the first visit, the study doctor will check who can take part. For those who can take part, participants will visit the clinic or hospital when they get their next bleed. They will receive TAK-672 slowly through a vein. This is called an infusion. They might need extra infusions of TAK-672 to control the bleed. After their bleed is controlled, participants will regularly visit the clinic for a check-up and to treat any further bleeds. This will happen until all participants have received their last dose of TAK-672 to control their 1st bleed. After this, all participants will visit the clinic 90 days later for a final check-up.

Being tested
TAK-672
Medical subject headings
Factor 8 deficiency, acquired

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TAK-672Biological

    Also called rpFVIII, TAK-672, Obizur

    B-Domain Deleted Recombinant Porcine Factor VIII

Study groups in NCT04580407
Study groupRoleWhat they receive
TAK-672ExperimentalTAK-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.
Receives: Biological: TAK-672

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Severe Bleeding Episodes Who Demonstrated Response to TAK-672 Therapy at 24 Hours After the Initiation of Treatment

    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%'.

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

Secondary outcomes (19)
  1. Percentage of Participants With Severe Bleeding Episodes Successfully Controlled With TAK-672 Therapy, as Assessed by the Investigator

    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.

    Measured: 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)

  2. 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

    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.

    Measured: 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

  3. Frequency of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes

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

    Measured: 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)

  4. Total Dose of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes

    '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.

    Measured: 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)

  5. Total Number of Infusions Per Participant of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes

    '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.

    Measured: 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)

  6. Percentage of Participants With Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes

    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.

    Measured: 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

  7. Mean Value of Pre-infusion Anti-TAK-672 Antibody Titers in Participants With Successful Control of the Bleeding Episode

    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.

    Measured: 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)

  8. Mean Value of Total Dose Per Participant in Participants With Successful Control of the Bleeding Episode

    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.

    Measured: 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)

  9. Number of Participants With Positive Response at 24 Hours After the Initiation of Treatment in Participants With Successful Control of the Bleeding Episode

    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).

    Measured: 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)

  10. Anti-hFVIII Inhibitor Titers

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

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

  11. Anti-pFVIII Inhibitor Titer

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

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

  12. Terminal Half-life (t1/2) for TAK-672

    Measured: Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672

  13. Clearance (CL) for TAK-672

    Measured: Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672

  14. Volume of Distribution (Vd) for TAK-672

    Measured: Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672

  15. Area Under the Concentration-Time Curve (AUC) for TAK-672

    Measured: Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with the initial dose of TAK-672

  16. Maximum Drug Concentration (Cmax) Per Dose (Cmax/Dose) for TAK-672

    Measured: Pre-dose and at multiple time points post-dose (up to 24 hours) after over 48 hours from the last treatment with TAK-672

  17. Duration Period From Initial Dose of TAK-672 Until Completion of Hemostasis Control

    Measured: 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)

  18. Total Dose Per Participant From Initial Dose of TAK-672 Until Completion of Hemostasis Control

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

    Measured: 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)

  19. Number of Participants With New Qualified Severe Bleeding Episodes

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2020
  2. Study start9 Apr 2021
  3. Primary completion29 Nov 2022
  4. Study completion29 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04580407
Sponsor's protocol ID
TAK-672-3001
Other IDs
U1111-1258-0779, jRCT2051200066
Status last verified
Oct 2024
First submitted
5 Oct 2020
Last updated
2 Dec 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing TAK-672 in people with Acquired Hemophilia A, run by Takeda at 9 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Severe Bleeding Episodes Who Demonstrated Response to TAK-672 Therapy at 24 Hours After the Initiation of Treatment (time frame: 24 hours after the initial dose of TAK-672). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2024.

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