Clinical trial NCT05150340: A Study of TAK-771 in Japanese People With Primary Immunodeficiency Diseases (PID)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency Diseases (PID)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-12-09
Enrollment: 16
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Epoch 2: Serum Trough Levels of Total IgG Antibodies After Administration of TAK-771
timeFrame: 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:
measure: Epoch 2: Maximum Concentration (Cmax) of Total Serum Levels of IgG and IgG Subclasses
timeFrame: 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.
measure: Epoch 2: Time to Maximum Concentration (Tmax) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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.
measure: Epoch 2: Area Under the Curve (AUC) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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.
measure: Epoch 2: Half-life of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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
measure: Epoch 2: Apparent Total Clearance (CL/F) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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.
measure: Epoch 2: Apparent Volume of Distribution (Vz/F) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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.
measure: Epoch 2: Minimum Concentration (Cmin) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
timeFrame: 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.
measure: Epoch 2: Serum Trough Levels of IgG Subclasses (IgG1, IgG2, IgG3, and IgG4) After Administration of TAK-771
timeFrame: 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)
measure: Epoch 1 and 2: Trough Levels of Anti-Clostridium Tetani Toxoid Antibody After Administration of TAK-771
timeFrame: 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)
measure: Epoch 1 and 2: Trough Levels of Anti-HBV Antibody After Administration of TAK-771
timeFrame: 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)
measure: Epoch 1 and 2: Trough Levels of Anti-HIB Antibody After Administration of TAK-771
timeFrame: 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).
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Percentage of Participants With TAK-771-Related and TAK-771-Non-Related TEAEs
timeFrame: 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
measure: Percentage of Participants With Serious and Non-serious TEAEs
timeFrame: 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
measure: Percentage of Participants With Severe TEAEs
timeFrame: 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
measure: Percentage of Participants With Local and Systemic TEAEs
timeFrame: 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
measure: Percentage of Participants With TEAEs Leading to Premature Discontinuation From Study
timeFrame: 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
measure: Percentage of Participants With Infusion-associated TEAEs
timeFrame: 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
measure: Percentage of Participants With Clinically Significant Changes in Clinical Laboratory Parameters Recorded as TEAEs
timeFrame: 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
measure: Percentage of Participants With Clinically Significant Changes in Vital Signs and Body Weight Recorded as TEAEs
timeFrame: 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
measure: Epoch 2: Percentage of Participants Who Develop Anti-rHuPH20 Binding Antibody Titers of Greater Than or Equal to 1:160
timeFrame: 4-Week Dosing Interval (Week 7, Week 19, and Week 31); 3-Week Dosing Interval (Week 4, Week 16, and Week 28)
measure: Epoch 2: Percentage of Participants Who Develop Neutralizing Antibodies to rHuPH20
timeFrame: 4-Week Dosing Interval (Week 7, Week 19, and Week 31); 3-Week Dosing Interval (Week 4, Week 16, and Week 28)
measure: Percentage of Participants Who Experienced Tolerability Events Related to the Infusion of TAK-771
timeFrame: 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
measure: Epoch 1: Number of Weeks to Reach Final Dose Interval (3 Weeks or 4 Weeks)
timeFrame: Up to Week 4 for Participants with 4-Week Dosing Interval or Up to Week 3 for Participants with 3-Week Dosing Interval
measure: Epoch 2: Percentage of Participants Who Achieve a Treatment Interval of 3 or 4 Weeks
timeFrame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval
measure: Epoch 2: Percentage of Participants Who Maintain a Treatment Interval of 3 or 4 Weeks
timeFrame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval
measure: Annual Rate of Validated Acute Serious Bacterial Infections (ASBIs) Per Participant Per Year
timeFrame: 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
measure: Annual Rate of All Infections Per Participant Per Year
timeFrame: 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
measure: Healthcare Resource Utilization: Days Not Able To Attend School/Work or To Perform Normal Daily Activities Due to Illness/Infection
timeFrame: 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
measure: Healthcare Resource Utilization: Days on Antibiotics
timeFrame: 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
measure: Healthcare Resource Utilization: Number of Hospitalizations Due to Illness/Infection Per Year
timeFrame: 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
measure: Healthcare Resource Utilization: Length of Stay in Days of Hospitalizations Due to Illness/Infection Per Participant Per Year
timeFrame: 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
measure: Healthcare Resource Utilization: Number of Acute (Urgent or Unscheduled) Physician Visits Due to Illness/Infection
timeFrame: 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
measure: Infusion Parameters in Epoch 2: Number of Infusion Sites Per Infusion
timeFrame: 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
measure: Infusion Parameters in Epoch 2: Number of Infusion Sites Per Month
timeFrame: 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
measure: Infusion Parameters in Epoch 2: Duration of Individual Infusions
timeFrame: 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
measure: Infusion Parameters in Epoch 2: Maximum Infusion Rate Per Site
timeFrame: 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
measure: Infusion Parameters in Epoch 2: Infusion Volume Per Site
timeFrame: 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
measure: Quality of Life (QOL): Pediatric Quality of Life Inventory (PEDS-QL)
timeFrame: 4-Week Dosing Interval (Week 1 and Week 31); 3-Week Dosing Interval (Week 1 and Week 28)
measure: QOL: Short Form-36 Health Survey Version 2 (SF-36 v2)
timeFrame: 4-Week Dosing Interval (Week 1 and Week 31); 3-Week Dosing Interval (Week 1 and Week 28)
measure: QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire Index Score
timeFrame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)
measure: QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire Visual Analogue Scale (VAS) Score
timeFrame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)
measure: Treatment Preference
timeFrame: Up to Week 31 for Participants with 4-Week Dosing Interval or Up to Week 28 for Participants with 3-Week Dosing Interval
measure: Treatment Satisfaction: Questionnaire for Medication-9 (TSQM-9)
timeFrame: 4-Week dosing interval (Week 1 and Week 31); 3-Week dosing interval (Week 1 and Week 28)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kitakyushu
country: Japan
facility: Hospital of University of Occupational and Environmental Health
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Yokohama
country: Japan
facility: Kanagawa Children's Medical Center
state: Kanagawa
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Bunkyo-ku
country: Japan
facility: Tokyo Medical Dental University Hospital
state: Tokyo
city: Setagaya-ku
country: Japan
facility: National Center for Child Health and development
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Gifu
country: Japan
facility: Gifu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Saitama
country: Japan
facility: Saitama Prefectual Children's Medical Center
city: Shizuoka
country: Japan
facility: Shizuoka Childrens Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: