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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 3, Open-label, Non-controlled Study to Evaluate the Pharmacokinetics, Safety and Tolerability, and Efficacy of TAK-771 in Japanese Subjects With Primary Immunodeficiency Diseases (PID)

Conditions
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Primary Immunodeficiency Diseases (PID)

Intervention / Treatment
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* Drug: TAK-771


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Be a Japanese person. 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. 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. 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. Serum trough levels at screening/enrollment meet one of the following: 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. 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. Participant is willing and able to comply with use of digital tools and applications. Exclusion Criteria 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. 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) Participant has presence of renal function impairment defined by eGFR <60 mL/min/1.73m^2. 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. 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. Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome) Participant has anemia that would preclude phlebotomy for laboratory studies according to standard practice at the site. 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 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. 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. 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 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. Participant has total protein >9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia. Participant has a known allergy to hyaluronidase Participant has severe dermatitis that would preclude adequate sites for safe product administration.

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epoch 1: TAK-771 Ramp up Period<br>TAK-771 includes Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20). Participants will receive subcutaneous infusion of rHuPH20 solution at a dose of 80 U/g IgG first, followed by SC infusion of 10% IGI within 10 minutes of completion of the infusion of rHuPH20 solution. The dose of 10% IGI will be increased from 1/3 of full dose to full dose in 3 weeks for participants who will receive TAK-771 once every 3 week, or from 1/4 of full dose to full dose in 6 weeks for participants who will receive TAK-771 once every 4 week. | Drug: TAK-771<br>* Intervention description; Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20)<br>* Other names: Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase;|
| Experimental: Epoch 2: TAK-771 Treatment Period<br>TAK-771 includes Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20). Participants will receive subcutaneous infusion of rHuPH20 solution at a dose of 80 U/g IgG first, followed by SC infusion of 10% IGI within 10 minutes of completion of the infusion of rHuPH20 solution, every 3, or 4 weeks for up to Week 24. | Drug: TAK-771<br>* Intervention description; Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20)<br>* Other names: Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epoch 2: Serum Trough Levels of Total IgG Antibodies after Administration of TAK-771 |  | Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epoch 2: Maximum Concentration (Cmax) of Total Serum Levels of IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants 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) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants with 3-Week Dosing Interval) | 
| Epoch 2: Area Under the Curve (AUC) of Total Serum Levels of IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants with 3-Week Dosing Interval) | 
| Epoch 2: Half-life of Total Serum Levels of IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants 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) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants with 3-Week Dosing Interval) | 
| Epoch 2: Apparent Volume of Distribution (Vz/F) of Total Serum Levels of IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants with 3-Week Dosing Interval) | 
| Epoch 2: Minimum Concentration (Cmin) of Total Serum Levels of IgG and IgG subclasses (IgG1, IgG2, IgG3, and IgG4) |  | Day 1 predose and multiple timepoints postdose (up to 4 weeks for Participants with 4-Week Dosing Interval for Participants with 3-Week Dosing Interval) | 
| Epoch 2: Serum Trough Levels of IgG subclasses (IgG1, IgG2, IgG3, and IgG4) after Administration of TAK-771 |  | 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: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens after Administration of TAK-771 | Clinically relevant pathogens will be Clostridium tetani toxoid, Haemophilus influenzae (HIB) and Hepatitis B virus (HBV). | 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: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens after Administration of TAK-771 | Clinically relevant pathogens will be Clostridium tetani toxoid, Haemophilus influenzae (HIB) and Hepatitis B virus (HBV). | 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 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. | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 Neutralizing Antibodies to rHuPH20 |  | 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 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. | 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) |  | 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 |  | 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 |  | 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) | Annual rate of validated acute serious bacterial infections (ASBIs) per participant will be reported. | 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 | Annual rate of all infections per participant will be reported. | 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 |  | 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 |  | 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 |  | 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 |  | 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 |  | 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 Infusions per Month |  | 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 |  | 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 Month |  | 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: Duration of Individual Infusions |  | 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: Maximum Infusion Rate per Site |  | 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: Infusion Volume per Site |  | Up to Week 31 for Participants with 4-Week Dosing Interval or 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. | Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval | 
| 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. | Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval | 
| QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire | EQ-5D-3L health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. In this study, 2-11 years (parent as observer),12 years and older (participant as observer) for EQ-5D-3L health questionnaire will be analyzed. The EQ-5D-3L total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome. | 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: Life Quality Index (LQI) | The LQI is a self-administered questionnaire developed specifically for participants/legal guardians involved in intravenous immunoglobulin (IVIG) treatments. In this study, 2-13 years (parent as observer), 14 years and older (participant as observer) for LQI health questionnaire will be analyzed. LQI consists of 15-items, divided into four domains: treatment interferences (6 items), therapy-related problems (4 items), therapy setting (3 items), and treatment costs (2 items). Items are rated on a 7-point Likert-type scale ranging from 1: Extremely bad to 7: Extremely good. Total scores range from 15 to 105, with higher scores indicating the highest possible satisfaction with factors such as independence, therapy convenience, social/school/work activities, and health and travel costs. | 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. | Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval | 
| 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 therapy, the participant's rating on the frequency and method of administration, and the participant's preference to continue receiving the IGSC treatment. | Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval |