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

Study Overview
=================
Brief Summary
-----------------
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 7days after the infusion to check side effect from the study treatment.

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

Official Title
-----------------
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

Conditions
-----------------
Congenital Protein C Deficiency

Intervention / Treatment
-----------------
* Drug: TAK-662


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: PK Part: Male and female participants with Japanese nationality. A diagnosis of congenital protein C deficiency (homozygous or compound heterozygous). Asymptomatic participant. Oral anticoagulants allowed to be received. Extension part: Participants who participated in the PK part of this study (TAK-662-1501). 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: Current or recurrent disease that could affect the action, or disposition of the investigational product (IP), or clinical or laboratory assessments. A body weight less than 8 kg. Serious liver dysfunction, judged by the investigator. Any thrombosis within 2 weeks prior to administration of the IP. Other investigational product than TAK-662 received within 60 days prior to the administration of the IP. 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. 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. Known or suspected intolerance or hypersensitivity to the IP, closely-related compounds, or any of the stated ingredients. Known history of alcohol or other substance abuse within the last year. 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).
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-662 80 IU/kg<br>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<br>* Lyophilized, sterile concentrate of human protein C<br>* Other names: Protein C Concentrate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protein C activity |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| Terminal Phase Elimination Half-life (t1/2) for TAL-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| Incremental recovery (IR) for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| In-vivo recovery (IVR) for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| Cmax: Maximum Observed Plasma Concentration for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-662 |  | Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36 hours Post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-Related Adverse Experiences (AEs) | An AE is defined as any untoward medical occurrence in a clinical investigation subject administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g. a clinically significant abnormal laboratory value), symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug. | Up to Day 7 | 
| Extension Part: Treatment of Acute Episodes Rated by Efficacy Rating Scale | The treatment of acute episodes (purpura fulminans [PF] / coumarin-induced skin necrosis [CISN] / warfarin-induced skin necrosis [WISN] and/or other vascular thromboembolic events) will be rated according to the efficacy rating scale; as effective, effective with complications, or not effective, when it is determined that the next infusion will be unnecessary. | Up to Day 10 (Duration may vary depending on symptoms) | 
| Extension Part: Percentage of Participants who Experience Surgical Episodes during Short-Term Prophylaxis | Percentage of participants who will experience surgical episodes during short-term prophylaxis in extension part will be reported. TAK-662 will be utilized as short-term prophylaxis, that will be free of presentations of PF or thromboembolic complications. | Up to Day 10 (Duration may vary depending on symptoms) | 
| 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 in extension part will be reported. | Up to 1.5 years |