A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency
- Registration Number
- NCT04984889
- Lead Sponsor
- Takeda
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 5
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.
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:
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TAK-662 80 IU/kg TAK-662 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.
- Primary Outcome Measures
Name Time Method 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: 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: 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: 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).
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.
- Secondary Outcome Measures
Name Time Method 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.
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.
Trial Locations
- Locations (4)
Chiba Children's Hospital
🇯🇵Chiba, Japan
Nara Medical University Hospital
🇯🇵Kashihara, Nara, Japan
Chiba University Hospital
🇯🇵Chiba, Japan
Saitama Prefectural Children's Medical Center
🇯🇵Saitama, Japan