A Study of TAK-881 in Participants With Primary Immunodeficiency Diseases (PIDD)

Sponsor

Takeda (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05755035

Collaborator

Takeda Development Center Americas, Inc. (Industry)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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 or HYQVIA with the same dose and dosing interval of immunoglobulin for up to 32 weeks 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.

Condition or Disease	Intervention/Treatment	Phase
Primary Immunodeficiency Diseases (PID)	Biological: TAK-881 Biological: HYQVIA	Phase 2/Phase 3

Detailed Description

The study consists of a screening epoch, a ramp-up epoch and treatment epochs. Participants who have been receiving intravenous IgG (IVIG), 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, including those rolling over from previous studies (TAK-771-3004 [NCT05513586]/ TAK-771-3005 [NCT05150340]), 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. Participants aged 2 to less than [<]16 years will complete a nonrandomized treatment epoch (TAK-881 only).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

61 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This study consists of crossover randomized part (participants aged >=16 years) and non-randomized part (participants aged 2 to <16 years).This study consists of crossover randomized part (participants aged >=16 years) and non-randomized part (participants aged 2 to <16 years).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 29, 2023

Anticipated Primary Completion Date :

Apr 28, 2025

Anticipated Study Completion Date :

Apr 28, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Randomized Crossover Treatment Epoch: TAK-881 followed by HYQVIA (Sequence 1) Participants aged >=16 years will receive 4 or 5 full doses of TAK-881 followed by 4 or 5 full doses HYQVIA in sequence 1. The first full dose of TAK-881 or HYQVIA, depending on the sequence, will be administered either 2 weeks after the ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin IgG treatment (if ramp-up is not applicable).	Biological: TAK-881 Participants will receive SC infusion of TAK-881 on Day 1. Other Names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20). Biological: HYQVIA Participants will receive SC infusion of HYQVIA on Day 1. Other Names: Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20). TAK-771
Experimental: Randomized Crossover Treatment Epoch: HYQVIA followed by TAK-881 (Sequence 2) Participants aged >=16 years will receive 5 full doses of HYQVIA followed by 4 or 5 full doses of TAK-881 in Sequence 2. The first full dose of TAK-881 or HYQVIA, depending on the sequence, will be administered either 2 weeks after the ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin IgG treatment (if ramp-up is not applicable).	Biological: TAK-881 Participants will receive SC infusion of TAK-881 on Day 1. Other Names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20). Biological: HYQVIA Participants will receive SC infusion of HYQVIA on Day 1. Other Names: Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20). TAK-771
Experimental: Non-Randomized Treatment Epoch: TAK-881 Participants aged 2 to <16 years will receive 4 to 5 full doses of TAK-881. The first full dose of TAK-881, will be administered either 2 weeks after the 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 Participants will receive SC infusion of TAK-881 on Day 1. Other Names: Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).

Arm

Intervention/Treatment

Experimental: Randomized Crossover Treatment Epoch: TAK-881 followed by HYQVIA (Sequence 1)

Participants aged >=16 years will receive 4 or 5 full doses of TAK-881 followed by 4 or 5 full doses HYQVIA in sequence 1. The first full dose of TAK-881 or HYQVIA, depending on the sequence, will be administered either 2 weeks after the ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin IgG treatment (if ramp-up is not applicable).

Biological: TAK-881

Participants will receive SC infusion of TAK-881 on Day 1.

Other Names:

Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).

Biological: HYQVIA

Participants will receive SC infusion of HYQVIA on Day 1.

Other Names:

Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20).

TAK-771

Experimental: Randomized Crossover Treatment Epoch: HYQVIA followed by TAK-881 (Sequence 2)

Participants aged >=16 years will receive 5 full doses of HYQVIA followed by 4 or 5 full doses of TAK-881 in Sequence 2. The first full dose of TAK-881 or HYQVIA, depending on the sequence, will be administered either 2 weeks after the ramp-up dose (if applicable) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin IgG treatment (if ramp-up is not applicable).

Biological: TAK-881

Participants will receive SC infusion of TAK-881 on Day 1.

Other Names:

Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).

Biological: HYQVIA

Participants will receive SC infusion of HYQVIA on Day 1.

Other Names:

Immune Globulin Infusion (Human), 10% Solution with Recombinant Human Hyaluronidase (rHuPH20).

TAK-771

Experimental: Non-Randomized Treatment Epoch: TAK-881

Participants aged 2 to <16 years will receive 4 to 5 full doses of TAK-881. The first full dose of TAK-881, will be administered either 2 weeks after the 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

Participants will receive SC infusion of TAK-881 on Day 1.

Other Names:

Immune Globulin Subcutaneous (Human), 20% Solution with Recombinant Human Hyaluronidase (rHuPH20).

Outcome Measures

Primary Outcome Measures

Area Under the Curve During the Dosing Interval at Steady-State (AUC0-tau;ss) of TAK-881 and HYQVIA in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]

Secondary Outcome Measures

Maximum Concentration (Cmax) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
Time to Maximum Concentration (Tmax) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
Terminal half-life (t1/2) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
Apparent Clearance (CL/F) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
Apparent Volume of Distribution (Vz/F) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
AUC0-tau; ss Per Week (AUC0-tau; ss/week) of TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 years With PIDD [3- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15 and 22 pre- infusions; 4- Week dosing interval: PK Day 1 (pre-infusion and post-infusion), PK Days 2, 3, 4, 8, 15, 22 and 29 pre-infusion]
Trough Level of IgG in Participants Aged >=16 years With PIDD [From start of study drug administration up to Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
Trough Level of IgG Subclasses and Antigen Specific IgG Antibodies in Participants Aged >=16 years With PIDD [From start of study drug administration up to Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [From start of study drug administration up to Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
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 Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
Number of Participants With Positive Binding Antibodies (Titer Greater than and equal to [>=] 1:160) to rHuPH20 [From start of study drug administration up to Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
Number of Participants With Positive Neutralizing Antibodies to rHuPH20 [From start of study drug administration up to Week 31 (for 3-week regimen) and Week 33 (for 4-week regimen)]
Trough Level of Total IgG, IgG Subclasses and Antigen Specific IgG Antibodies in Participants Aged 2 to <16 years With PIDD [From start of study drug administration up to Week 16 (for 3-week regimen) and Week 17 (for 4-week regimen)]
Number of Infusions per Month at Full Dose With Both TAK-881 and HYQVIA in all Participants [Up to Weeks 16 and 31 (3-week regimen) and Weeks 17 and 33 (for 4-week regimen)]
Number of infusions per month at full dose with both TAK-881 and HYQVIA in all participants will be assessed.
Number of Infusions Sites per Infusion at Full Dose With Both TAK-881 and HYQVIA in all Participants [Up to Weeks 16 and 31 (3-week regimen) and Weeks 17 and 33 (for 4-week regimen)]
Number of infusions sites per infusion at full dose both TAK-881 and HYQVIA in all participants will be assessed.
Duration of Infusions at Full Dose With Both TAK-881 and HYQVIA in all Participants [Up to Weeks 16 and 31 (3-week regimen) and Weeks 17 and 33 (for 4-week regimen)]
Duration of infusions at full dose with both TAK-881 and HYQVIA in all participants will be assessed.
Monthly Infusion Time at Full Dose With Both TAK-881 and HYQVIA in all Participants [Time from the start of rHuPH20 infusion until the stop time of IgG infusion (Up to Week 38)]
Monthly infusion time at full dose with both TAK-881 and HYQVIA in all participants will be assessed.
Maximum Infusion Rate per Site at Full Dose With Both TAK-881 and HYQVIA in all Participants [Time from the start of rHuPH20 infusion until the stop time of IgG infusion (Up to Week 38)]
Maximum infusion rate per site at full dose with both TAK-881 and HYQVIA in all participants will be assessed.
Infusion Volume per Site at Full Dose With Both TAK-881 and HYQVIA in all Participants [Time from the start of rHuPH20 infusion until the stop time of IgG infusion (Up to Week 38)]
Infusion volume per site at full dose with both TAK-881 and HYQVIA in all participants will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 screening for the nonrandomized part of the study OR 16 years or older at the time of screening for the randomized 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 300 milligrams per kilograms per body weight per 4 weeks (mg/kg BW/4 weeks). Variations in the treatment interval of up to +=3 days or monthly IgG absolute dose amount of up to +=20 percent (%) are acceptable.
Participant has a serum trough level of IgG greater than (>) 5 grams per liter (g/L) at the following time points:

IVIG- or HYQVIA-treated participants: At screening (sample taken prior to last prestudy IgG infusion and after signing the ICF) and at least 1 documented serum IgG trough level of >5 g/L within 12 weeks prior to screening.
TAK-771-3004 or TAK-771-3005 participants: Documented serum IgG trough level of

5 g/L at the last 2 visits before the end of study or end of trial (EOS/ET) visit in Japan studies TAK-771-3004 or TAK-771-3005.

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/legally authorized representative is willing and able to comply with the requirements of the protocol.

Informed Consent

The participant or the participant's legally authorized representative, is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
The participant / Participant's legally authorized representative 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.
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 (except for participants rolling over from Japan studies TAK-771-3004 or TAK-771-3005).
Participant who experiences a clinically significant AE in Japan studies TAK-771-3004 or TAK-771-3005 and it may worsen by participating in this study at the discretion of the investigator.
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.
If female, participant is pregnant or lactating at the time of screening.