Study of TAK-672 in Participants With Acquired Hemophilia A

NCT04580407 | Completed Phase 2 Results

• 3 other identifiers: TAK-672-3001U1111-1258-0779jRCT2051200066
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Acquired Hemophilia A

Outcome Measures

Primary Outcomes (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%'.

  24 hours after the initial dose of TAK-672

Secondary Outcomes (19)

• Percentage of Participants With Severe Bleeding Episodes Successfully Controlled With TAK-672 Therapy, as Assessed by the Investigator

  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)

• 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

  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

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

  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)

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

  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)

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

  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)

Study Arms (1)

TAK-672

EXPERIMENTAL

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.

Biological: TAK-672

Interventions

TAK-672 BIOLOGICAL

B-Domain Deleted Recombinant Porcine Factor VIII

Also known as: rpFVIII, TAK-672, Obizur

TAK-672

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (9)

Gunma University Hospital

Maebashi, Gunma, Japan

Location

Nagoya University Hospital

Aichi, Nagoya, Japan

Location

Nara Medical University Hospital

Kashihara-shi, Nara, Japan

Location

Uonuma Kikan Hospital

Minamiuonuma, Niigata, Japan

Location

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Location

Tokyo Saiseikai Central Hospital

Mita, Tokyo, Japan

Location

Chiba University Hospital

Chiba, Japan

Location

Fukushima Medical University Hospital

Fukushima, Japan

Location

Yamagata University Hospital

Yamagata, Japan

Location

Related Links

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

MeSH Terms

Conditions

Factor 8 deficiency, acquired

Interventions

Factor VIII

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Results Point of Contact

• Title: Study
• Organization: Director

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 8, 2020
• Study Start: April 9, 2021
• Primary Completion: November 29, 2022
• Study Completion: November 29, 2022
• Last Updated: December 2, 2024
• Results First Posted: December 2, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (9)