An Extension Study of TAK-664 for Japanese People With Primary Immunodeficiency Disease

A Phase 3, Open-label, Non-controlled, Multi-dose, Extension Study to Evaluate the Long-term Safety and Tolerability of IGSC, 20% in Japanese Subjects With Primary Immunodeficiency Disease (PID)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04842643

Enrollment

Registered

2021-04-13

Start date

2021-04-27

Completion date

2024-04-25

Last updated

2025-01-20

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

Conditions

Primary Immunodeficiency Disease

Brief summary

This study is an extension study for participants with primary immunodeficiency disorders who were previously treated with IGSC, 20% in the TAK-664-3001 study. They must have completed that study or be about to complete it before joining this study. Participants will continue treatment with IGCS, 20% in this study. The main aim of this study is to check for side effects from long-term treatment with IGSC, 20% . This medicine is not yet licensed in Japan, so participants will be treated with IGSC, 20% until it becomes commercially available.

Interventions

BIOLOGICALIGSC 20% infusion

IGSC 20% infusion,

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Participant has completed or is about to complete Takeda Clinical Study TAK-664-3001. A participant is considered to have completed Study TAK-664-3001 successfully if they fulfill the following criterion: Completed Epoch 2, in which IGSC, 20% is administered weekly (completion of Epoch 3, in which IGSC, 20% is administered biweekly, is not mandatory for participation in TAK-664-3002 study). 2. Written informed consent is obtained from either the Participant or the Participant's legally authorized representative prior to any study-related procedures and study product administration. 3. Participant is willing and able to comply with the requirements of the protocol.

Exclusion criteria

1. Participant has developed a new serious medical condition during participation in Study TAK-664-3001 such that the Participant's safety or medical care would be impacted by participation in the extension study TAK-664-3002. 2. Participant is scheduled to participate in another non-Takeda clinical study involving an Investigational Product or device-used-in-clinical-trial in the course of this study. 3. If a female of childbearing potential, Participant is pregnant or has a negative pregnancy test but does not agree to employ adequate birth control measures for the duration of the study.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	TEAEs were defined as adverse events (AEs) with onset after date-time of first dose of study drug (intravenous immunoglobulin \[IGIV\] or IGSC), or medical conditions present prior to the start of study drug (IGIV or IGSC) but increased in severity or relationship after date-time of first dose of study drug (IGIV or IGSC). A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.
Number of Participants With Drug-related and Non-related TEAEs	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	TEAEs were defined as adverse events (AEs) with onset after date-time of first dose of study drug (intravenous immunoglobulin \[IGIV\] or IGSC), or medical conditions present prior to the start of study drug (IGIV or IGSC) but increased in severity or relationship after date-time of first dose of study drug (IGIV or IGSC). Any TEAE that was recorded by the investigator as probably related or possibly related to study drug was considered as study drug related AE, and any AE recorded as unlikely related or not related was considered as unrelated AE.
Number of Participants With Severe, Local and Systemic TEAEs	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	A severe TEAE was an AE that caused considerable interference with the participant's usual activities. Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term administration site reactions or contained the phrase injection site or infusion site. Systemic TEAEs were defined as AEs that were not included in the Medical Dictionary for Regulatory Activities (MedDRA) Higher Level Group Term administration site reactions and did not contain the phrase injection site or infusion site.
Number of Participants With TEAEs Leading to Premature Discontinuation From Study and Infusion-associated TEAEs	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	Infusion associated TEAEs were defined as any TEAE that began during study drug infusion or within 72 hours of completion of study drug infusion. TEAEs leading to premature discontinuation from study and infusion-associated TEAEs were reported.

Secondary

Measure	Time frame	Description
Number of Days Participants Not Able to Attend School or Work to Perform Normal Daily Activities Due to Illness/Infection	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	Number of days not able to attend school or work to perform normal daily activities due to illness/infection are standardized per year (365.25 days). Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Number of Days Participants on Antibiotics	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	Number of days on antibiotics was defined as the number of days those antibiotics were taken as concomitant medications and was standardized to per year (365.25 days). Number of days participants on antibiotics were reported. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Number of Hospitalizations Due to Illness or Infection	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	Number of hospitalizations were standardized to per year (365.25 days). Hospitalizations were measured by asking participants to report the number of nights they have stayed overnight in the hospital during the year, for something related to their own health. Number of hospitalizations due to illness or infection were reported. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Serum Trough Levels of Total Immune Globulin G (IgG) and IgG1, IgG2, IgG3, IgG4 Antibodies Subclasses Following Weekly Administration of IGSC, 20%	At end of treatment in the current extension study TAK-664-3002 (i.e. 3 years)	Serum trough levels of total IgG and IgG1, IgG2, IgG3, IgG4 antibodies subclasses were determined by using standard assay methods.
Number of Acute Physician Visits Due to Illness/Infection	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	Number of acute physician visits is standardized to per year (365.25 days). Number of acute (urgent or unscheduled) physician visits due to illness/infection were reported. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Number of Participants With Their Response for Treatment Preference Questionnaire	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	Treatment preference questionnaire is a self-administered questionnaire developed to assess participant's preference towards the administration of new IGSC therapy. There are 4-items on the questionnaire, which investigate a participant's preference on the clinic/hospital/home setting of receiving the immunoglobulin therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment. For First question Before participation in the trial(s), where did you receive your immunoglobulin therapy participants were allowed to select multiple answers for options (At the hospital; At home; Other) for their treatment. As a result, the sum of responders in the arm IGSC, 20%: \>=14 Years for the first question were higher than the total number of participants analyzed in the category.
Number of Participants With Tolerability Events Related to the Infusion of Study Drug	From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose	An infusion was considered tolerable if the infusion rate was not reduced, or the infusion was not interrupted or stopped, due to a TEAE related to study drug infusion. A tolerability event was considered to have occurred if an infusion was not tolerable.
Length of Hospital Stay Due to Illness or Infection	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	Length of hospital stay per stay was standardized to per year (365.25 days). Number of days due to illness or infection were reported. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Serum Trough Levels of IgG and IgG1, IgG2, IgG3, IgG4 Antibodies Subclasses Following Biweekly Administration of IGSC, 20%	At end of treatment in the current extension study TAK-664-3002 (i.e. 3 years)	Serum trough levels of IgG and IgG1, IgG2, IgG3, IgG4 antibodies subclasses were determined by using standard assay methods.
Annual Rate of Validated Acute Serious Bacterial Infections (ASBI)	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	The ASBI rate was calculated as the mean number of acute serious bacterial infections per participants per year. Annual rate of validated acute serious bacterial infections per participant was assessed. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.
Annual Rate of All Infections	From first dose of study drug in core study TAK-664-3001 up to end of current extension study TAK-664-3002 (up to approximately 4.5 years)	The annual rate of infections was calculated as the mean number of infections per participant per year. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.

Countries

Japan

Participant flow

Recruitment details

Participants took part in the study at 8 investigative sites in Japan from 27 April 2021 to 25 April 2024.

Pre-assignment details

Participants with primary immunodeficiency disorders who completed core study TAK-664-3001 (NCT04346108) were enrolled to receive Immune globulin subcutaneous (IGCS), 20 percent (%) in this current extension study (TAK-664-3002 \[NCT04842643\]). As per planned analysis, the data was collected, analyzed and reported for a single arm only and per dose level wise data was not collected in this study.

Participants by arm

Arm	Count
IGSC, 20% Participants who completed Epoch 2 of core study TAK-664-3001 (NCT04346108), received between 50 to 200 mg/kg of IGSC infusion, 20% infusion once a week (Epoch 2 regimen) and 100 to 400 mg/kg of IGSC infusion, 20% biweekly (Epoch 3 regimen) until the study drug becomes commercially available.	12
Total	12

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Other	1
Overall Study	Physician Decision	1

Baseline characteristics

Characteristic	IGSC, 20%
Age, Continuous	36.0 years STANDARD_DEVIATION 21.68
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	12 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	5 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 12
other Total, other adverse events	12 / 12
serious Total, serious adverse events	3 / 12

Outcome results

Primary

Number of Participants With Drug-related and Non-related TEAEs

TEAEs were defined as adverse events (AEs) with onset after date-time of first dose of study drug (intravenous immunoglobulin \[IGIV\] or IGSC), or medical conditions present prior to the start of study drug (IGIV or IGSC) but increased in severity or relationship after date-time of first dose of study drug (IGIV or IGSC). Any TEAE that was recorded by the investigator as probably related or possibly related to study drug was considered as study drug related AE, and any AE recorded as unlikely related or not related was considered as unrelated AE.

Time frame: From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose

Population: All-Treated Set consisted of all enrolled participants who received IGSC, 20% administration at least once in this study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IGSC, 20%	Number of Participants With Drug-related and Non-related TEAEs	Drug-related TEAEs	9 Participants
IGSC, 20%	Number of Participants With Drug-related and Non-related TEAEs	Non-related TEAEs	12 Participants

Primary

Number of Participants With Severe, Local and Systemic TEAEs

A severe TEAE was an AE that caused considerable interference with the participant's usual activities. Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term administration site reactions or contained the phrase injection site or infusion site. Systemic TEAEs were defined as AEs that were not included in the Medical Dictionary for Regulatory Activities (MedDRA) Higher Level Group Term administration site reactions and did not contain the phrase injection site or infusion site.

Time frame: From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose

Population: All-Treated Set consisted of all enrolled participants who received IGSC, 20% administration at least once in this study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IGSC, 20%	Number of Participants With Severe, Local and Systemic TEAEs	Severe TEAEs	3 Participants
IGSC, 20%	Number of Participants With Severe, Local and Systemic TEAEs	Local TEAEs	8 Participants
IGSC, 20%	Number of Participants With Severe, Local and Systemic TEAEs	Systemic TEAEs	12 Participants

Primary

Number of Participants With TEAEs Leading to Premature Discontinuation From Study and Infusion-associated TEAEs

Infusion associated TEAEs were defined as any TEAE that began during study drug infusion or within 72 hours of completion of study drug infusion. TEAEs leading to premature discontinuation from study and infusion-associated TEAEs were reported.

Time frame: From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose

Population: All-Treated Set consisted of all enrolled participants who received IGSC, 20% administration at least once in this study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IGSC, 20%	Number of Participants With TEAEs Leading to Premature Discontinuation From Study and Infusion-associated TEAEs	TEAEs Leading to Premature Discontinuation	0 Participants
IGSC, 20%	Number of Participants With TEAEs Leading to Premature Discontinuation From Study and Infusion-associated TEAEs	Infusion-associated TEAEs	12 Participants

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs

TEAEs were defined as adverse events (AEs) with onset after date-time of first dose of study drug (intravenous immunoglobulin \[IGIV\] or IGSC), or medical conditions present prior to the start of study drug (IGIV or IGSC) but increased in severity or relationship after date-time of first dose of study drug (IGIV or IGSC). A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.

Time frame: From the first dose of the study drug in the current extension study TAK-664-3002, up to 3 years post-dose

Population: All-Treated Set consisted of all enrolled participants who received IGSC, 20% administration at least once in this study.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
IGSC, 20%	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs	TEAEs	12 Participants
IGSC, 20%	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs	Serious TEAEs	3 Participants
IGSC, 20%	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and Non-serious TEAEs	Non-serious TEAEs	12 Participants

Secondary

Annual Rate of All Infections

The annual rate of infections was calculated as the mean number of infections per participant per year. Reported timeframe included timeframe of core study TAK-664-3001 (NCT04346108) (Max approximately 1.5 year) and of current extension study (Max approximately 3 years) as data of this outcome measure was collected from first dose of core study to end of current extension study and the data is presented for participants who entered in current study from core study as per plan.