Study of TAK-672 in Participants With Acquired Hemophilia A

• Register: ClinicalTrials.gov
• Last refreshed on: 9 January 2023
• Main ID: NCT04580407
• Date of registration: 05/10/2020
• Prospective Registration: Yes
• Primary sponsor: Takeda
• Public title: Study of TAK-672 in Participants With Acquired Hemophilia A
• Scientific 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)
• Date of first enrolment: November 9, 2021
• Target sample size: 5
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT04580407
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Japan

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female Japanese participants of >=18 years of age.

2. 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.

3. 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

- Confirmation of a low FVIII:C.

- Positive FVIII inhibitor (>=0.6 BU) as measured either in the local or central
laboratory

4. 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).

5. 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.

6. Participants with expected life expectancies of at least 90 days prior to the onset of
the hemorrhagic episode.

7. 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.

8. Participant who are able to willing and able to comply with the requirements of the
protocol.

Exclusion Criteria:

1. Participants with an established reason for bleeding that is not correctable even with
hemostatic therapy.

2. Participants presenting a bleeding episode that is assessed likely to resolve on its
own, even if left untreated.

3. 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).

4. 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.

5. 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.

6. Participants who are currently pregnant or breastfeeding, or planning to become
pregnant or father a child during the study

7. 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.

8. 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.

9. Participants who are unable to or unwilling to comply with the study design, protocol
requirements, and/or the follow-up procedures.

10. Participants whose majority of age are under legal protection.

11. 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.

12. Participants who are judged by the investigator as being ineligible for any other
reason.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acquired Hemophilia A

Intervention(s)

Biological: TAK-672

Primary Outcome(s)

Percentage of Severe Bleeding Episodes with Demonstrated Response to TAK-672 Therapy at 24 Hours after the Initiation of Treatment [Time Frame: 24 hours after the initiation of treatment]

Secondary Outcome(s)

Correlation between the Response at 24 Hours and the Eventual Control of the Bleeding Episode [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Maximum Drug Concentration (Cmax) per Dose (Cmax/Dose) for TAK-672 [Time Frame: Pre-dose and at multiple time points (up to 24 hours) post-dose]

The Overall Percentage of Severe Bleeding Episodes Successfully Controlled with TAK-672 Therapy, as Assessed by the Investigator [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Terminal Half-life (t1/2) for TAK-672 [Time Frame: Pre-dose and at multiple time points (up to 24 hours) post-dose]

Total Dose from Initial Dose of TAK-672 until Completion of Hemostasis Control [Time Frame: Time of completion of hemostasis control (varied from participant to participant)]

Clearance (CL) for TAK-672 [Time Frame: Pre-dose and at multiple time points (up to 24 hours) post-dose]

The Percentage of Bleeding Episodes Responsive to TAK-672 Therapy at Designated Assessment Time Points after the Initiation of Therapy, as Assessed by the Investigator [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Area Under the Concentration-Time Curve (AUC) for TAK-672 [Time Frame: Pre-dose and at multiple time points (up to 24 hours) post-dose]

Total Dose of Infusions of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes. [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

Total Number of Infusions of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

Volume of Distribution (Vd) for TAK-672 [Time Frame: Pre-dose and at multiple time points (up to 24 hours) post-dose]

Anti-pFVIII Inhibitor Level [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Number of new qualified severe bleeding episodes [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Anti-hFVIII Inhibitor Level [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Correlation among the Total Dose of TAK-672 and the Eventual Control of the Bleeding Episode [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Correlation between Response to TAK-672 Therapy at Specified Time Points and Eventual Control of Severe Bleeding Episodes [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Frequency of Infusions of TAK-672 Required to Successfully Control Qualifying Bleeding Episodes [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

Correlation among the Pre-infusion Anti-TAK-672 Antibody Titers and the Eventual Control of the Bleeding Episode [Time Frame: Up to 1 year (90 days after final treatment dosing)]

Duration Period from Initial Dose of TAK-672 until Completion of Hemostasis Control [Time Frame: Time of completion of hemostasis control (varied from participant to participant)]

Secondary ID(s)

U1111-1258-0779

TAK-672-3001

jRCT2051200066

Source(s) of Monetary Support

Please refer to primary and secondary sponsors