A Study About How TAK-881 is Processed by the Body and Side Effects in People With Primary Immunodeficiency Diseases

Study Overview
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Brief Summary
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The main aim of this study is to evaluate the PK, safety, tolerability and immunogenicity of subcutaneous (SC) administration of TAK-881 in adult and pediatric participants with PIDD and compare them to HYQVIA in participants 16 years old and older. The participants will be treated with TAK-881/HYQVIA or HYQVIA/TAK-881 with the same dose and dosing interval of immunoglobulin for up to 51 weeks (for participants greater than or equal to [>=]16 years) and only with TAK-881 for up to 27 weeks (for participants aged 2 to less than [<]16 years) as they were treated with another immunoglobulin before enrollment. Participants will need to visit the clinic every 3 or 4 weeks during the duration of the study.

Detailed Description
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The study consists of a screening epoch, a ramp-up epoch (if needed) and treatment epochs. Participants who have been receiving intravenous IgG (IVIG) before the study, will enter a ramp-up epoch which will start 3 or 4 weeks after the last IVIG pre study dose before screening. Participants who have already been receiving HYQVIA treatment before the study, will directly enter the treatment epochs after screening. Participants aged greater than or equal to [>=]16 years will be randomized at a 1:1 ratio to one of the following treatment sequences: either TAK-881 followed by HYQVIA or HYQVIA followed by TAK-881. Each participant aged greater than or equal to [>=]16 years will complete both crossover epochs. Pediatric participants aged 2 to less than [<]16 years will complete a single arm treatment with the study drug (TAK-881 only).

Official Title
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Multicenter, Prospective, Open-label, Randomized, Crossover Study to Evaluate Pharmacokinetics (PK), Safety, and Tolerability of TAK-881 in Primary Immunodeficiency Diseases (PIDD)

Conditions
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Primary Immunodeficiency Diseases (PID)

Intervention / Treatment
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* Biological: TAK-881
* Biological: HYQVIA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring immunoglobulin (IgG) replacement, as defined according to the International Union of Immunological Societies (IUIS) Committee. Participant is 2 years to <16 years at the time of signing the informed consent form (ICF) for the single arm treatment part of the study OR 16 years or older at the time of signing the ICF for the crossover part of the study. Participant has received regular intravenous immune globulin (IVIG) or HYQVIA with a treatment interval of every 21 or 28 days over a period of at least 12 weeks prior to screening at a minimum dose of 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks). Variations in the treatment interval of up to ±5 days are acceptable. Participant has a serum trough level of IgG greater than (>) 5 grams per liter (g/L) at screening (sample taken prior to last prestudy IgG infusion and after signing the ICF). If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ an acceptable form of contraception for the duration of the study. Participant/Parent/Legal Guardian is willing and able to comply with the requirements of the protocol. Informed Consent The participant or the participant's parent/legal guardian is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator. The participant / Participant's parent/legal guardian has provided informed consent/assent, if applicable, (that is, in writing, documented via a signed and dated ICF and/or eConsent, if available), and any required privacy authorization prior to the initiation of any study procedures. Exclusion Criteria Participant has a known history of or is positive at screening 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. Abnormal laboratory values at screening 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* the upper limit of normal (ULN) for the testing laboratory. Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] less than and equal to (<=) 500 per cubic millimeter (/mm^3). Known history of chronic kidney disease, or glomerular filtration rate (GFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m^2). Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site, at the discretion of the investigator. Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or immune serum globulin infusions. Known substance or prescription drug abuse within 12 months of screening. Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L) with known anti-IgA antibodies and a history of hypersensitivity. Participant has a known allergy to hyaluronidase. Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening. Participant has a bleeding disorder, or a platelet count less than 20,000 per microliter (mcL), or in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of immune globulin subcutaneous (IGSC) therapy. History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device >2 years prior to screening are allowed. Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening. Participant is scheduled to participate in another clinical study involving an IP (except for participants scheduled to enroll in a long-term follow-up study with TAK-881) or investigational device during the course of this study. Participant is a family member or employee of the investigator or the investigator's site staff. If female, participant is pregnant or lactating at the time of screening.

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: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study consists of crossover randomized epoch (participants aged >=16 years) and single arm epoch (participants aged 2 to <16 years).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Crossover Treatment Epoch: TAK-881 followed by HYQVIA (Sequence 1)<br>Participants aged >=16 years will receive 6 or 8 full doses of TAK-881 followed by 6 or 8 full doses HYQVIA in sequence 1. The first full dose of TAK-881 will be administered either 2 weeks after the second ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin G (IgG) treatment (if ramp-up is not applicable). | Biological: TAK-881<br>* Participants will receive SC infusion of TAK-881.<br>* Other names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).;Biological: HYQVIA<br>* Participants will receive SC infusion of HYQVIA.<br>* Other names: Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20).;|
| Experimental: Randomized Crossover Treatment Epoch: HYQVIA followed by TAK-881 (Sequence 2)<br>Participants aged >=16 years will receive 6 or 8 full doses of HYQVIA followed by 6 or 8 full doses of TAK-881 in Sequence 2. The first full dose of HYQVIA will be administered either 2 weeks after the second ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study IgG treatment (if ramp-up is not applicable). | Biological: TAK-881<br>* Participants will receive SC infusion of TAK-881.<br>* Other names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).;Biological: HYQVIA<br>* Participants will receive SC infusion of HYQVIA.<br>* Other names: Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20).;|
| Experimental: Single Arm Treatment Epoch: TAK-881<br>Pediatric participants aged 2 to <16 years will receive 6 or 8 full doses of TAK-881. The first full dose of TAK-881, will be administered either 2 weeks after the second ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study IgG treatment (if ramp-up is not applicable). | Biological: TAK-881<br>* Participants will receive SC infusion of TAK-881.<br>* Other names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve During the Dosing Interval at Steady-State (AUC0-tau;ss) of total IgG with TAK-881 and HYQVIA in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Rate of all Infections in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Annualized Rate of Acute Serious Bacterial Infections (ASBIs) in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Annualized Rate of Episodes of Fever in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Time to First ASBI in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Duration of Infections in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Days Lost From School, Work, Daycare, or to Perform Normal Daily Activities Due To Infection and/or their treatment or other Illnesses (non-Infection) |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Days on Antibiotics in Participants |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Hospitalizations With Indications (Infection or other Illnesses) |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Days of Hospitalization |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Acute Physician Visits (Office and Emergency Room) Due to Infection or Other Illnesses |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Maximum Concentration (Cmax) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| Time to Maximum Concentration (Tmax) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| Terminal half-life (t1/2) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| Apparent Clearance (CL/F) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| Apparent Volume of Distribution (Vz/F) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| AUC0-tau; ss Per Week (AUC0-tau; ss/week) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 14, 21, 28 days (post-infusion) of last infusion in each cross-over epoch | 
| Maximum Concentration (Cmax) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| Time to Maximum Concentration (Tmax) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| Terminal half-life (t1/2) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| Apparent Clearance (CL/F) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| Apparent Volume of Distribution (Vz/F) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| AUC0-tau; ss Per Week (AUC0-tau; ss/week) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD |  | 3-Week dosing: Day 1 (pre and post-infusion), 24, 48, 72 hours and 7, 14, 21 days (post-infusion); 4-Week dosing: Day 1 (pre and post-infusion), 24, 48 and 72 hours and 7, 21, 28 days (post-infusion) | 
| Trough Level of Total IgG in Participants Aged 2 to <16 Years and >=16 Years with PIDD |  | Up to 27 Weeks (2 to <16 years) and 51 Weeks (>=16 years) | 
| Trough Level of IgG Subclasses in Participants Aged 2 to <16 Years and >=16 Years with PIDD |  | Up to 27 Weeks (2 to <16 years) and 51 Weeks (>=16 years) | 
| Trough Level of Antigen Specific IgG Antibodies in Participants Aged 2 to <16 Years and >=16 Years with PIDD |  | Up to 27 Weeks (2 to <16 years) and 51 Weeks (>=16 years) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |  | Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years) | 
| Number of Participants With Infusion Withdrawals, Interruptions, and Infusion Rate Reductions due to TAK-881-related TEAEs |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Number of Participants With Positive Binding Antibodies (Titer Greater than and equal to [>=] 1:160) and With Positive Neutralizing Antibodies to rHuPH20 |  | From start of study drug administration, up to 25 Week (2 to <16 years) and 49 Week (>=16 years) | 
| Number of Infusions per Month at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Duration of Infusions (minutes) at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Monthly Infusion (minutes/month) Time at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Number of Infusions Sites (Needle Sticks) per Infusion at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Number of Infusions Sites (Needle Sticks) per Month at Full Dose With Both TAK-881 and HYQVIA in all Participant |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Maximum Infusion Rate per Site (mL/hour/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 
| Infusion Volume per Site (mL/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants |  | From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulin; primary immunodeficiency disease, Immunoglobulin replacement therapy; facilitated subcutaneous