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

JRCT ID: jRCT2031210457

Registered date:27/11/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Primary Immunodeficiency Diseases (PID)
• Date of first enrollment: 24/01/2022
• Target sample size: 16
• Study type: Interventional

Intervention(s)

Epoch 1: TAK-771 Ramp up Period
TAK-771 includes Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20). Participants will receive SC 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.

Epoch 2: TAK-771 Full Dose Treatment Period
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.

Outcome(s)

Primary Outcome

1.Epoch 2: Serum Trough Levels of Total IgG Antibodies after Administration of TAK-771
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
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.

Secondary Outcome

1.-7. Epoch 2: Maximum Concentration (Cmax), Time to Maximum Concentration (Tmax), Area Under the Curve (AUC), Half-life, Apparent Total Clearance (CL/F), Apparent Volume of Distribution (Vz/F) and Minimum Concentration (Cmin) of Total Serum Levels of IgG and IgG Subclasses (IgG1, IgG2, IgG3, and IgG4)
Time Frame: Pre-infusion at the last dose of TAK-771 (Week 27 for participants with 4-Week dosing interval or Week 25 for participants 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 for participants with 3-Week dosing interval

8. 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)

9.-11. Epoch 1 and 2: Trough Levels of Anti-Clostridium Tetani Toxoid Antibody, Anti-HBV Antibody and 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)

12. Percentage of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From Week 1, up to Week 31 for Participants with 4-Week Dosing or up to Week 28 for Participants with 3-Week Dosing Interval

13. 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

14. Percentage of Participants with Serious and Non-serious 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

15.-18. Percentage of Participants with Severe TEAEs, Local and Systemic TEAEs, TEAEs Leading to Premature Discontinuation from Study and 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

19.-20. Percentage of Participants with Clinically Significant Changes in Clinical Laboratory Parameters, 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

21.-22. Epoch 2: Percentage of Participants who Develop Anti-rHuPH20 Binding Antibody Titers of Greater Than or Equal to 1:160 and 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)

23. Percentage of Participants who Experienced Tolerability Events Related to the Infusion of TAK-771
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
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.

24. Epoch 1: Number of Weeks to Reach Final Dose Interval (3 Weeks or 4 Weeks)
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
The number of weeks to reach final dose interval is defined as treatment duration of Epoch 1.

25.-26. Epoch 2: Percentage of Participants who Achieve a Treatment Interval of 3 or 4 Weeks and 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

27. Annual Rate of Validated Acute Serious Bacterial Infections (ASBIs)
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
The annual rate of validated ASBIs is calculated as the mean number of ASBIs per participant per year. The data was collected using poisson estimate. Point-estimate and 99% confidence bound (i.e., the upper bound of two-sided 98% confidence interval) were calculated using a Poisson model with subject-year in study as the offset variable.

28. Annual Rate of All Infections per Participant
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
The annual rate of all infections is calculated as the mean number of infections per participant per year.

29.-33. Healthcare Resource Utilization: Days Not Able To Attend School/Work or To Perform Normal Daily Activities Due to Illness/Infection, Days on Antibiotics, Number of Hospitalizations Due to Illness/Infection, Length of Stay in Days of Hospitalizations Due to Illness/Infection and 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

34. Infusion Parameters in Epoch 2: Number of Infusion Sites per Infusion
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
Total number of infusion sites injected in Epoch 2 / Total number of infusions administered in Epoch 2.

35. Infusion Parameters in Epoch 2: Number of Infusion Sites per Month
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
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.

36. Infusion Parameters in Epoch 2: Duration of Individual Infusions
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
End date and time of infusion in Epoch 2-Start date and time of infusion in Epoch 2, for each infusion per participant.

37. Infusion Parameters in Epoch 2: Maximum Infusion Rate per Site
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
Maximum Infusion Rate results from CRF / number of infusion sites/body.

38. Infusion Parameters in Epoch 2: Infusion Volume per Site
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 Volume per Site is scheduled Dose results from CRF / number of infusion sites/body.

39. Quality of Life (QOL): Pediatric Quality of Life Inventory (PEDS-QL)
Time Frame: 4-Week dosing interval (Week 1, Week 19, and Week 31); 3-Week dosing interval (Week 1, Week 16, and Week 28)

40. QOL: Short Form-36 Health Survey Version 2 (SF-36 v2)
Time Frame: 4-Week dosing interval (Week 1, Week 19, and Week 31); 3-Week dosing interval (Week 1, Week 16, and Week 28)

41. QOL: EuroQoL (Quality of Life)-5 Dimensions 3 Levels (EQ-5D-3L) Health Questionnaire
Time Frame: 4-Week dosing interval (Week 1, Week 19, and Week 31); 3-Week dosing interval (Week 1, Week 16, and Week 28)

42. Treatment Preference
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

43. Treatment Satisfaction: Questionnaire for Medication-9 (TSQM-9)
Time Frame: 4-Week dosing interval (Week 1, Week 19, and Week 31); 3-Week dosing interval (Week 1, Week 16, and Week 28)

Key inclusion & exclusion criteria

• Age minimum: >= 2age old
• Age maximum: Not applicable
• Gender: Both

Include 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:
a. 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.
b. 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.

Exclude 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.

Related Information

• Primary Sponsor: Nishizawa Atsushi
• Secondary ID(s): NCT05150340