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

Primary Immunodeficiency Diseases (PID) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05755035
• Other study ID #: TAK-881-3001
• Secondary ID: 2022-502095-23
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 24, 2023
• Est. completion date: September 30, 2026

Study information

• Verified date: April 2024
• Source: Takeda
• Contact: Takeda Contact
• Phone: +1-877-825-3327
• Email: medinfoUS[@]takeda.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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/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.

Description:

The study consists of a screening epoch, a ramp-up epoch (if needed) and treatment epochs. Participants who have been receiving conventional subcutaneous intravenous immunoglobin G (cIGSC) or intravenous immunoglobulin G (IGIV) before the study, will enter a ramp-up epoch which will start 1, 2, 3 or 4 weeks after the last cIGSC or IGIV 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 >=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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: September 30, 2026
• Est. primary completion date: February 10, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

Inclusion Criteria

• Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring 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 a stable dose of regular treatment with any IGIV OR HYQVIA with a treatment interval of every 21 or 28 days OR any cIGSC with a treatment interval of every 7 or 14 days over a period of at least 12 weeks prior to screening at a minimum prestudy IgG dose equivalent to 0.3 grams per kilograms per body weight per 4 weeks (g/kg BW/4 weeks) and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the participant should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than +-25 percentage (%) from the mean dose for all IgG infusions within this 12-week period prior to screening. Variations in the treatment interval of up to +-5 days for participant with a 28-day treatment interval and of up to +-3 days for participant with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.

• Participant has a serum trough level of IgG greater than (>) 5 grams per liter (g/L) at the following time points:

1. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and

2. Within 12 weeks prior to screening.

• If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ highly effective form of contraception for the duration of the study.

• Participant/Participant's parent(s)/legal guardian(s) is/are willing and able to comply with the requirements of the protocol, including PK blood sampling, for the duration of the study.

Informed Consent

• The participant or the participant's parents/legal guardians is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.

• The participant/Participant's parents/legal guardians has/have 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 a positive result 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. Cured participants with a history of hepatitis C infection who have a negative PCR test at screening is eligible.

• Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):

1. Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5* the upper limit of normal (ULN) for the testing laboratory.

2. 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 estimated glomerular filtration rate (eGFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) at screening.

• 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.

• Participants with a known systemic hypersensitivity to any of the excipients of TAK-881/HYQVIA in accordance with the Investigator's Brochure (IB)/package insert/Summary of Product Characteristics (SmPC).

• Known substance or prescription drug abuse within 12 months of screening.

• Participant has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L) associated with known anti-IgA antibodies and a history of hypersensitivity.

• Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.

• 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.

• Treatment with immunosuppressants including chemotherapeutic agents, immunomodulators, and long-term systemic corticosteroid (defined as a daily dose of >1 mg of prednisone equivalent/kg/day for >30 days) within 12 weeks prior to screening. Short or intermittent courses (<=10 days) of corticosteroids are allowed.

• Live-attenuated viral vaccination within 12 weeks prior to screening.

• 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 a medical condition, laboratory finding, or physical examination finding that precludes participation, or with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the study or place the participant at undue medical risk.

• 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.

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immunodeficiency Diseases
• Primary Immunodeficiency Diseases (PID)

Intervention

Biological:
• TAK-881
Participants will receive SC infusion of TAK-881.
• HYQVIA
Participants will receive SC infusion of HYQVIA.

Locations

Country	Name	City	State
United States	Optimed Research, LTD	Columbus	Ohio
United States	Central Georgia Infectious Disease Consultants	Macon	Georgia
United States	Tanner Clinic	Murray	Utah
United States	Sneeze, Wheeze, & Itch Associates, LLC	Normal	Illinois
United States	Vital Prospects Clinical Research Institute, PC	Tulsa	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Annualized Rate of all Infections in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Annualized Rate of Acute Serious Bacterial Infections (ASBIs) in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Annualized Rate of Episodes of Fever in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Time to First ASBI in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Duration of Infections in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Number of Days Lost From School, Work, Daycare, or to Perform Normal Daily Activities Due To Infection and/or their treatment or other Illnesses		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Number of Days on Antibiotics in Participants		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Number of Hospitalizations With Indications (Infection or other Illnesses)		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Number of Days of Hospitalization		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	Number of Acute Physician Visits Due to Infection or Other Illnesses		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Trough Level of Antigen Specific IgG Antibodies in Participants Aged >=16 Years with PIDD		Up to 51 Weeks
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)		Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
Secondary	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)
Secondary	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 22 Week (2 to <16 years) and 46 Week (>=16 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

•   To obtain more information on the study, click here/on this link