A Study of TAK-771 in Japanese People With Primary Immunodeficiency Diseases (PID)

Takeda16 enrolled

Overview

The main aim of the study is to check how much TAK-771 stays in their blood over time, side effect from the study treatment or TAK-771, how much TAK-771 participants can receive without getting side effects from it, and if TAK-771 improves symptoms of primary immunodeficiency diseases (PID). This will help the study sponsor (Takeda) to work out the best dose to give people in the future. The participants will be treated with TAK-771 for totally 27 or 30 weeks. Treatment period is consist of two periods called Epoch 1 and Epoch 2. In Epoch 1, different groups of participants will receive lower to higher doses of TAK-771 for 3 to 6 weeks. The study doctors will check for side effects from each dose of TAK-771. In Epoch 2, participants will receive TAK-771 once a 3 or 4 weeks until the end of 24 weeks. There will be many clinic visits. The number of visits will depend on the infusion cycles of study drug (every 3, or 4 weeks).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Primary Immunodeficiency Diseases (PID)

Interventions

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

Inclusion Criteria 1. Be a Japanese person. 2. Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies(IUIS) Committee 2017. The diagnosis must be confirmed by the Medical Director prior to TAK-771 treatment. 3. Participant has been receiving a stable clinical dose of intravenous immunoglobulin (IVIG) or conventional subcutaneous immunoglobulin (cSCIG), which is equivalent to approximately 200 to 600 mg/kg body weight per 3 to 4 week period for IVIG and approximately 50 to 200 mg/kg body weight per week for cSCIG based on the description in the package insert, consistently over a period of at least 3 months prior to screening, or Participant has been receiving of TAK-664 with fixed dose and dosing frequency at least 3 months prior to enrollment. That is, participant is about to complete Study TAK-664-3001 or participating in Study TAK-664-3002. 4. Participant who has been receiving IVIG or cSCIG had all serum trough levels of total immunoglobulin G (IgG) \>=5 g/L within 1 month prior to the screening/enrollment. 5. Serum trough levels at screening/enrollment meet one of the following: 1. IVIG-treated or cSCIG-treated participants Participant who had serum trough levels of IgG \>=5 g/L at the last 2 points in screening procedure before the first administration of TAK-771. 2. TAK-664-treated participants Participant who had serum trough levels of IgG \>=5 g/L at the last 2 points in TAK-664 studies before the first administration of TAK-771. 6. Participant is willing and able to comply with use of digital tools and applications. Exclusion Criteria 1. Participant has a known history of or is positive at screening/enrollment for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2 For participants who are switching from TAK-664 studies, the eligibility will be reconfirmed after result of the specialty test conducted at Week 1 become available. 2. Abnormal laboratory values at screening/enrollment meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent): * Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \>2.5 times the upper limit of normal (ULN) for the testing laboratory * Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] =\<500/mm\^3) 3. Participant has presence of renal function impairment defined by eGFR \<60 mL/min/1.73m\^2. 4. Participant has been diagnosed with, or had a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the disease-free period prior to screening exceeds 5 years. 5. Participant is receiving anti-coagulation therapy or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening/enrollment or a history of thrombophilia. 6. Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome) 7. Participant has anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site. 8. Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IVIG, subcutaneous immunoglobulin (SCIG), and/or Immune Serum Globulin infusions 9. Participant has immunoglobulin A (IgA) deficiency (serum IgA less than 0.07g/L) and history of hypersensitivity, or history of confirmed anti-IgA antibodies, or both. 10. Participant is on preventative (prophylactic) systemic antibacterial antibiotics at doses sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics at the time of screening/enrollment. 11. Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening/enrollment or had a serious bacterial infection within the 3 months prior to screening/enrollment 12. Participant has a bleeding disorder, or a platelet count less than 20,000/microL, or in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous (SC) therapy. 13. Participant has total protein \>9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia. 14. Participant has a known allergy to hyaluronidase 15. Participant has severe dermatitis that would preclude adequate sites for safe product administration.

Locations (12)

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Hospital of University of Occupational and Environmental Health

Kitakyushu, Fukuoka, Japan

Kurume University Hospital

Kurume, Fukuoka, Japan

Kanagawa Children's Medical Center

Yokohama, Kanagawa, Japan

Shinshu University Hospital

Matsumoto, Nagano, Japan

Tokyo Medical Dental University Hospital

Bunkyo-ku, Tokyo, Japan

National Center for Child Health and development

Setagaya-ku, Tokyo, Japan

Kyushu University Hospital

Fukuoka, Japan

Gifu University Hospital

Gifu, Japan

Hiroshima University Hospital

Hiroshima, Japan

...and 2 more locations

Outcomes

Primary Outcomes

Epoch 2: Serum Trough Levels of Total IgG Antibodies After Administration of TAK-771

The data was reported at Week 7, 11, 15, 19, 23, 27, and 31 for 4-Week interval and at Week 4, 7, 10, 13, 16, 19, 22, 25 and 28 for 3-Week interval.

Time frame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval

Secondary Outcomes

Epoch 2: Maximum Concentration (Cmax) of Total Serum Levels of IgG and IgG Subclasses

Time frame: Pre-infusion at Week 27 for participants with 4-Week or Week 25 with 3-Week dosing interval and post infusion at multiple time points up to Week 31 for participants with 4-Week dosing interval and up to Week 28 with 3-Week dosing interval.

Epoch 2: Time to Maximum Concentration (Tmax) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

Epoch 2: Area Under the Curve (AUC) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

AUC is expressed as grams\*day per liter/grams per kilograms \[(g\*day/L)/(g/kg)\].

Epoch 2: Half-life of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

Time frame: At multiple time points post-infusion from Week 7 for participants with 4-Week or Week 4 with 3-Week dosing interval up to Week 31 for participants with 4-Week dosing interval and up to Week 28 with 3-Week dosing interval

Epoch 2: Apparent Total Clearance (CL/F) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

Epoch 2: Apparent Volume of Distribution (Vz/F) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

Epoch 2: Minimum Concentration (Cmin) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)

Epoch 2: Serum Trough Levels of IgG Subclasses (IgG1, IgG2, IgG3, and IgG4) After Administration of TAK-771

Time frame: 4-Week dosing interval (Week 7, Week 11, Week 15, Week 19, Week 23, Week 27, and Week 31); 3-Week dosing interval (Week 4, week 7, Week 10, Week 16, Week 19, Week 22, Week 25, and Week 28)

Epoch 1 and 2: Trough Levels of Anti-Clostridium Tetani Toxoid Antibody After Administration of TAK-771

Time frame: From Week 1, up to end of trial (EOS: Week 31 for participants with 4-Week dosing interval or Week 28 for participants with 3-Week dosing interval)

Epoch 1 and 2: Trough Levels of Anti-HBV Antibody After Administration of TAK-771

Time frame: From Week 1, up to end of trial (EOS: Week 31 for participants with 4-Week dosing interval or Week 28 for participants with 3-Week dosing interval)

Epoch 1 and 2: Trough Levels of Anti-HIB Antibody After Administration of TAK-771

Time frame: From Week 1, up to end of trial (EOS: Week 31 for participants with 4-Week dosing interval or Week 28 for participants with 3-Week dosing interval).

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs are defined as Adverse events (AEs) with onset after date-time of first dose of Investigational product (IP), or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP.

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With TAK-771-Related and TAK-771-Non-Related TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Serious and Non-serious TEAEs

TEAEs are defined as AEs with onset after date-time of first dose of IP, or medical conditions present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Serious TEAE=any untoward clinical manifestation of signs, symptoms, outcomes (related to IP or not) at any dose: results in death, was life-threatening, requires inpatient/prolongation of hospitalization, resulted in persistent/significant disability/incapacity, congenital abnormality/birth defect, important medical event. AESI=investigator-reported hypersensitivity reactions, events of disordered coagulation as bleeding/hypercoagulable AESI.

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Severe TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Local and Systemic TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With TEAEs Leading to Premature Discontinuation From Study

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Infusion-associated TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Recorded as TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Percentage of Participants With Clinically Significant Changes in Vital Signs and Body Weight Recorded as TEAEs

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Epoch 2: Percentage of Participants Who Develop Anti-rHuPH20 Binding Antibody Titers of Greater Than or Equal to 1:160

Time frame: 4-Week Dosing Interval (Week 7, Week 19, and Week 31); 3-Week Dosing Interval (Week 4, Week 16, and Week 28)

Epoch 2: Percentage of Participants Who Develop Neutralizing Antibodies to rHuPH20

Time frame: 4-Week Dosing Interval (Week 7, Week 19, and Week 31); 3-Week Dosing Interval (Week 4, Week 16, and Week 28)

Percentage of Participants Who Experienced Tolerability Events Related to the Infusion of TAK-771

Tolerability events is defined as a case that the infusion rate is reduced, or that the infusion is interrupted or stopped, due to a TEAE related to TAK-771 infusion.

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Epoch 1: Number of Weeks to Reach Final Dose Interval (3 Weeks or 4 Weeks)

The number of weeks to reach final dose interval is defined as treatment duration of Epoch 1.

Time frame: Up to Week 4 for Participants with 4-Week Dosing Interval or Up to Week 3 for Participants with 3-Week Dosing Interval

Epoch 2: Percentage of Participants Who Achieve a Treatment Interval of 3 or 4 Weeks

Time frame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval

Epoch 2: Percentage of Participants Who Maintain a Treatment Interval of 3 or 4 Weeks

Time frame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval

Annual Rate of Validated Acute Serious Bacterial Infections (ASBIs) Per Participant Per Year

The annual rate of validated ASBIs is calculated as the mean number of ASBIs per participant per year.

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Annual Rate of All Infections Per Participant Per Year

The annual rate of all infections is calculated as the mean number of infections per participant per year.

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Healthcare Resource Utilization: Days Not Able To Attend School/Work or To Perform Normal Daily Activities Due to Illness/Infection

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Healthcare Resource Utilization: Days on Antibiotics

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Healthcare Resource Utilization: Number of Hospitalizations Due to Illness/Infection Per Year

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Healthcare Resource Utilization: Length of Stay in Days of Hospitalizations Due to Illness/Infection Per Participant Per Year

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Healthcare Resource Utilization: Number of Acute (Urgent or Unscheduled) Physician Visits Due to Illness/Infection

Time frame: From Week 1 up to Week 31 for Participants with 4-Week Dosing Interval or up to Week 28 for Participants with 3-Week Dosing Interval

Infusion Parameters in Epoch 2: Number of Infusion Sites Per Infusion

Total number of infusion sites injected in Epoch 2 / Total number of infusions administered in Epoch 2.

Time frame: From Week 7 up to Week 31 for Participants with 4-Week Dosing Interval or From Week 4 up to Week 28 for Participants with 3-Week Dosing Interval

Infusion Parameters in Epoch 2: Number of Infusion Sites Per Month

Total number of infusion sites injected in Epoch 2 / (duration of Epoch 2 / 30.4375), where duration of Epoch 2 is calculated as the end date of the Epoch 2 - the start date of the Epoch 2 + 1.

Time frame: From Week 7 up to Week 31 for Participants with 4-Week Dosing Interval or From Week 4 up to Week 28 for Participants with 3-Week Dosing Interval

Infusion Parameters in Epoch 2: Duration of Individual Infusions

End date and time of infusion in Epoch 2 - Start date and time of infusion in Epoch 2, for each infusion per participant.

Time frame: From Week 7 up to Week 31 for Participants with 4-Week Dosing Interval or From Week 4 up to Week 28 for Participants with 3-Week Dosing Interval

Infusion Parameters in Epoch 2: Maximum Infusion Rate Per Site

Maximum Infusion Rate results from CRF / number of infusion sites/body.

Time frame: From Week 7 up to Week 31 for Participants with 4-Week Dosing Interval or From Week 4 up to Week 28 for Participants with 3-Week Dosing Interval

Infusion Parameters in Epoch 2: Infusion Volume Per Site

Infusion Volume per Site is scheduled Dose results from CRF / number of infusion sites/body.

Time frame: From Week 7 up to Week 31 for Participants with 4-Week Dosing Interval or From Week 4 up to Week 28 for Participants with 3-Week Dosing Interval

Quality of Life (QOL): Pediatric Quality of Life Inventory (PEDS-QL)

The PEDS-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. In this study, 2-7 years (parent as observer), 8-13 years (participant as observer) for PEDS-QL health questionnaire will be analyzed. Higher scores indicate better quality of life (QOL) for all domains of the PEDS-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Four dimensions (physical, emotional, social, \& school functioning) are scored.

Time frame: 4-Week Dosing Interval (Week 1 and Week 31); 3-Week Dosing Interval (Week 1 and Week 28)

QOL: Short Form-36 Health Survey Version 2 (SF-36 v2)

The SF-36 is a generic quality-of-life instrument that has been widely used to assess Health-Related Quality of Life (HR QoL) of participants. In this study, 14 years and older (participant as observer) for SF-36 health questionnaire will be analyzed. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role - physical, bodily pain, general health, vitality, social functioning, role - emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HR QoL. Physical component summary (PCS).

Time frame: 4-Week Dosing Interval (Week 1 and Week 31); 3-Week Dosing Interval (Week 1 and Week 28)

QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire Index Score

The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to all participants to assess the effect of the treatment on the participants' quality of life. Participants select answer for each of the following 3-level dimensions: 1) mobility; 2) self-care; 3) usual activities; 4) pain/discomfort; 5) anxiety/depression used to compute an index score ranging from 0 (worst imaginable health state) to 1 (best imaginable health state). An increase in the EQ-5D-3L index score indicates improvement.

Time frame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)

QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire Visual Analogue Scale (VAS) Score

The EQ-5D-3L is a standardized instrument for use as a measure of health outcome and was administered to all participants to assess the effect of the treatment on the participants' quality of life. The EQ-5D-3L includes a visual analog scale (VAS), a vertical scale that allows the participants to indicate their health state that day, and ranges from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state.

Time frame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)

Treatment Preference

Treatment preference questionnaire is a self-administered questionnaire developed to assess participants' preference towards the administration of new subcutaneous immunoglobulin (SCIG) therapy. There are 4-items on the questionnaire, which investigate a participant's preference on the clinic/hospital/home setting of receiving the immunoglobulin (IG) therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment.

Time frame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval

Treatment Satisfaction: Questionnaire for Medication-9 (TSQM-9)

Treatment Satisfaction Questionnaire for Medication (TSQM) is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. In this study, 2-12 years (parent as observer), 13 years and older (participant as observer) for TSQM health questionnaire will be analyzed. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.

Time frame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)