A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency

An Open-Label, Single-Dose, Phase 1/2 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Human Protein C (TAK-662) for the Treatment of Congenital Protein C Deficiency in Japanese Subjects Followed by an Extension Part

Pharmacokinetic Part:

This study is for Japanese participants with congenital protein C deficiency. The main aim of this study is to check how much TAK-662 stays in their blood over time. This will help the study sponsor (Takeda) to work out the best dose to give patients in the future.

Participants will receive 1 single infusion of TAK-662.

They will stay at the clinic until 3 days after the infusion. Then, participants will return to their clinic 7 days after the infusion to check side effects from the study treatment.

Extension Part:

Participants who will complete the PK part will be given an opportunity to continue TAK-662 administration as 3 different treatment options (on-demand therapy, short-term prophylaxis, and long-term prophylaxis) in the Extension part, until the commercial protein C concentrate is available at each study site or study termination.

Study Overview

• Status: Completed
• Conditions: Congenital Protein C Deficiency
• Intervention / Treatment: Drug: TAK-662

Detailed Description

A Phase 1/2 Single-Dose Study of TAK-662 in Japanese Patients with Congenital Protein C Deficiency

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Chiba University Hospital
  • Chiba, Japan
    • Chiba Children's Hospital
  • Saitama, Japan
    • Saitama Prefectural Children's Medical Center
  • Nara
    • Kashihara, Nara, Japan
      • Nara Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

PK Part:

1. Male and female participants with Japanese nationality.
2. A diagnosis of congenital protein C deficiency (homozygous or compound heterozygous).
3. Asymptomatic participant.
4. Oral anticoagulants allowed to be received.

Extension part:

1. Participants who participated in the PK part of this study (TAK-662-1501).
2. Participant who are; a. Diagnosed with PF, CISN/WISN, and/or other acute thromboembolic episode for on-demand treatment only; b. Requiring treatment with TAK-662 for short-term prophylaxis for surgical procedures; c. Requiring treatment with TAK-662 for long-term prophylaxis.

Exclusion Criteria:

PK Part:

1. Current or recurrent disease that could affect the action, or disposition of the investigational product (IP), or clinical or laboratory assessments.
2. A body weight less than 8 kg.
3. Serious liver dysfunction, judged by the investigator.
4. Any thrombosis within 2 weeks prior to administration of the IP.
5. Other investigational product than TAK-662 received within 60 days prior to the administration of the IP.
6. Current or relevant history of physical or psychiatric illness, or any medical disorder that may require treatment or make the participant unlikely to fully complete the study, or any condition that presents undue risk from the IP or procedures.
7. Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) that could affect (improve or worsen) the condition being studied, or could affect the action or disposition of the IP, or clinical or laboratory assessment.
8. Known or suspected intolerance or hypersensitivity to the IP, closely-related compounds, or any of the stated ingredients.
9. Known history of alcohol or other substance abuse within the last year.
10. Within 30 days prior to the first dose of IP, a participant has been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this sponsored study.

Extension Part:

1. New serious medical conditions which could affect participant's safety or treatment were observed during participation in the PK part of this study (TAK-662-1501).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-662 80 IU/kg; TAK-662 80 international unit (IU)/kg, single intravenous infusion over 15 minutes on Day 1. In the extension part, dose of TAK-662 will be modified per participants. TAK-662 is Protein C Concentrate, which is a lyophilized, sterile concentrate of human protein C.	Drug: TAK-662; Lyophilized, sterile concentrate of human protein C; Other Names: Protein C Concentrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Part: Protein C Activity Level of TAK-662	Protein C is a vitamin K-dependent plasma protein and is an important component of the coagulation system. Protein C activity level was measured by chromogenic assays. Protein C activity level of TAK-662 was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662	t1/2 of TAK-662 was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Incremental Recovery (IR) of TAK-662	IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg).	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662	AUClast of TAK-662 was reported measured in terms of international unit*hour per milliliter (IU*h/ml).	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662	AUC0-infinity of TAK-662 was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662	Cmax of TAK-662 was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662	Tmax of TAK-662 was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662	IVR corrected for plasma was determined using the formula: IVR (percentage [%])= (Maximum observed plasma concentration (Cmax) [IU/mL] - Concentration (C) pre-infusion [IU/mL]) * Plasma volume pre-infusion (PV) milliliter (mL)/ Dose (international unit [IU])*100 where Cmax was the observed Cmax value before baseline correction. IVR of TAK-662 measured in terms of percentage was reported.	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs)	A treatment-related AE was defined as an adverse event that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which possible involvement of the drug was not able to be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant medications and concurrent treatments, might also be responsible. Number of participants with treatment-related AEs as assessed by the Investigator were reported.	PK Part: From the start of study drug administration up to Day 7; Extension Part: From the first dose of study drug administration in the Extension Part up to 35 months
Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment	The treatment of episodes of PF, CISN/ WISN, and/or other vascular thromboembolic events were rated as "effective", "effective with complications", or "not effective" according to the efficacy rating scale, as judged by investigators on the basis of following criteria, Effective: stabilization and regression of skin lesions/stabilization of thrombi; Effective with complications: treatment was effective but caused an adverse drug reaction that interfered with the regimen (resulted in change of dose or frequency of dosing) or forcing discontinuation of treatment or introducing pathogenic viral infection; Not effective: all other cases.	Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 months
Extension Part: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications	Percentage of surgical episodes for which TAK-662 was utilized as short-term prophylaxis that is free of presentations of PF or thromboembolic complications was reported.	Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 months
Extension Part: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis	Number of episodes of PF and/or thrombotic episodes during long-term prophylaxis was planned to be reported.	Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 months

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2021
• Primary Completion (Actual): March 29, 2022
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Blood Protein Disorders; Blood Coagulation Disorders, Inherited; Thrombophilia; Protein C Deficiency; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Protein C
• Other Study ID Numbers: TAK-662-1501; U1111-1267-4412 (Other Identifier: WHO); jRCT2031210209 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be reidentified (due to the limited number of study participants/study sites).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No