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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04984889

Enrollment

Registered

2021-08-02

Start date

2021-09-07

Completion date

2024-10-31

Last updated

2025-05-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Protein C Deficiency

Brief summary

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.

Interventions

DRUGTAK-662

Lyophilized, sterile concentrate of human protein C

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	Tmax of TAK-662 was reported.
PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	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.
PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	AUClast of TAK-662 was reported measured in terms of international unit\hour per milliliter (IU\h/ml).
PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	AUC0-infinity of TAK-662 was reported.
PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	Cmax of TAK-662 was reported.
PK Part: Protein C Activity Level of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	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.
PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	t1/2 of TAK-662 was reported.
PK Part: Incremental Recovery (IR) of TAK-662	Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion	IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg).

Secondary

Measure	Time frame	Description
Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment	Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 months	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: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications	Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 months	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: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis	Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 months	Number of episodes of PF and/or thrombotic episodes during long-term prophylaxis was planned to be reported.
PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs)	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	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.

Countries

Japan

Participant flow

Recruitment details

This study was conducted at 4 centers in Japan from 7 September 2021 to 31 October 2024.

Pre-assignment details

A total of 5 Japanese participants were enrolled in this 2-part study to receive TAK-662 in Pharmacokinetic (PK) part (Part 1) followed by 3 treatment options in the Extension part (Part 2) (on-demand, short-term, or long-term prophylaxis). As per planned analysis, the Extension Part data was collected, analyzed and reported as per On-demand and Short-term Prophylaxis treatments and per dose level wise data was not collected in this study.

Participants by arm

Arm	Count
PK Part: TAK-662 Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.	5
Total	5

Baseline characteristics

Characteristic	PK Part: TAK-662
Age, Continuous	15.2 years STANDARD_DEVIATION 8.87
Race/Ethnicity, Customized Japanese	5 Participants
Sex: Female, Male Female	1 Participants
Sex: Female, Male Male	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 4	0 / 1	0 / 0
other Total, other adverse events	2 / 5	3 / 4	0 / 1	0 / 0
serious Total, serious adverse events	0 / 5	0 / 4	0 / 1	0 / 0