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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 29, 2022

Interventions

  • Drug: TAK-662
    • Lyophilized, sterile concentrate of human protein C

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • PK Part: Protein C Activity Level of TAK-662
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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).
  • PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
    • Cmax of TAK-662 was reported.
  • PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662
    • Time Frame: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
    • Tmax of TAK-662 was reported.

Secondary Measures

  • Number of Participants With Treatment-Related Adverse Experiences (AEs)
    • Time Frame: From start of study drug administration up to Day 7
    • 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.
  • Extension Part: Treatment of Acute Episodes Rated by Efficacy Rating Scale
    • Time Frame: From Day 1 of Extension part up to end of study (up to approximately 35 months)
    • Data is not reported for this outcome measure as its analysis is still ongoing at the time of primary completion date and data will be reported after study completion.
  • Extension Part: Percentage of Participants Who Experience Surgical Episodes During Short-Term Prophylaxis
    • Time Frame: From Day 1 of Extension part up to end of study (up to approximately 35 months)
    • Data is not reported for this outcome measure as its analysis is still ongoing at the time of primary completion date and data will be reported after study completion.
  • Extension Part: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis
    • Time Frame: From Day 1 of Extension part up to end of study (up to approximately 35 months)
    • Data is not reported for this outcome measure as its analysis is still ongoing at the time of primary completion date and data will be reported after study completion.

Participating in This Clinical Trial

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).

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Takeda
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Study Director, Study Director, Takeda

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