Clinical trial NCT05755035: A Study About How TAK-881 is Processed by the Body and Side Effects in People With Primary Immunodeficiency Diseases
Official title: Multicenter, Prospective, Open-label, Randomized, Crossover Study to Evaluate Pharmacokinetics (PK), Safety, and Tolerability of TAK-881 in Primary Immunodeficiency Diseases (PIDD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Primary Immunodeficiency Diseases (PID)
Keywords: Immunoglobulin replacement therapy; facilitated subcutaneous
Immunoglobulin; primary immunodeficiency disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2023-03-06
Enrollment: 65
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study consists of crossover randomized epoch (participants aged \>=16 years) and single arm epoch (participants aged 2 to \<16 years).
Primary purpose: TREATMENT

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/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: 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).

Eligibility criteria: 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, or in the case of minors, legally designated representative(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, in the case of minors, legally designated representative(s) is/are willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
* The participant or, in the case of minors, legally designated representative(s) 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 a known 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.

Primary outcomes:
measure: 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
timeFrame: 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 outcomes:
measure: Annualized Rate of all Infections in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Annualized Rate of Acute Serious Bacterial Infections (ASBIs) in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Annualized Rate of Episodes of Fever in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Time to First ASBI in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Duration of Infections in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Days Lost From School, Work, Daycare, or to Perform Normal Daily Activities Due To Infection and/or their treatment or other Illnesses
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Days on Antibiotics in Participants
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Hospitalizations With Indications (Infection or other Illnesses)
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Days of Hospitalization
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Acute Physician Visits Due to Infection or Other Illnesses
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Maximum Concentration (Cmax) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD
timeFrame: 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
measure: Terminal half-life (t1/2) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD
timeFrame: 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
measure: Apparent Clearance (CL/F) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of total IgG with TAK-881 and HYQVIA at Steady-State in Participants Aged >=16 Years with PIDD
timeFrame: 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
measure: 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
timeFrame: 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
measure: Maximum Concentration (Cmax) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: Time to Maximum Concentration (Tmax) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: Terminal half-life (t1/2) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: Apparent Clearance (CL/F) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: Apparent Volume of Distribution (Vz/F) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: AUC0-tau; ss Per Week (AUC0-tau; ss/week) of TAK-881 at Steady-State in Participants Aged 2 to <= 16 Years with PIDD
timeFrame: 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)
measure: Trough Level of Total IgG in Participants Aged 2 to <16 Years and >=16 Years with PIDD
timeFrame: Up to 27 Weeks (2 to <16 years) and 51 Weeks (>=16 years)
measure: Trough Level of IgG Subclasses in Participants Aged 2 to <16 Years and >=16 Years with PIDD
timeFrame: Up to 27 Weeks (2 to <16 years) and 51 Weeks (>=16 years)
measure: Trough Level of Antigen Specific IgG Antibodies in Participants Aged >=16 Years with PIDD
timeFrame: Up to 51 Weeks
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 28 Weeks (2 to <16 years) and 52 Weeks (>=16 years)
measure: Number of Participants With Infusion Withdrawals, Interruptions, and Infusion Rate Reductions due to TAK-881-related TEAEs
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Number of Participants With Positive Binding Antibodies (Titer Greater than and equal to [>=] 1:160) and With Positive Neutralizing Antibodies to rHuPH20
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Number of Infusions per Month at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Duration of Infusions (minutes) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Monthly Infusion (minutes/month) Time at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Number of Infusions Sites (Needle Sticks) per Infusion at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Number of Infusions Sites (Needle Sticks) per Month at Full Dose With Both TAK-881 and HYQVIA in all Participant
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Maximum Infusion Rate per Site (mL/hour/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
measure: Infusion Volume per Site (mL/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: From start of study drug administration, up to 22 Week (2 to <16 years) and 46 Week (>=16 years)
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine Medical Center
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research
state: California
city: Denver
country: United States
facility: National Jewish Medical And Research Center
state: Colorado
city: Saint Petersburg
country: United States
facility: University of South Florida
state: Florida
city: Macon
country: United States
facility: Central Georgia Infectious Disease Consultants
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center - University Cardiovascular Surgeons
state: Illinois
city: Normal
country: United States
facility: Sneeze, Wheeze, & Itch Associates, LLC
state: Illinois
city: New Orleans
country: United States
facility: Louisiana State University Health Science Center-New Orleans
state: Louisiana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Durham
country: United States
facility: Duke Asthma, Allergy and Airway Center
state: North Carolina
city: Columbus
country: United States
facility: Optimed Research, LTD
state: Ohio
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, PC
state: Oklahoma
city: Dallas
country: United States
facility: Allergy Partners of North Texas
state: Texas
city: Murray
country: United States
facility: Tanner Clinic
state: Utah
city: Brno
country: Czechia
facility: University Hospital Brno (Fakultni Nemocnice Brno) - Children's Hospital (Detska nemocnice)
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne - ICRC
city: Prague
country: Czechia
facility: Fakultni Nemocnice v Motole
city: Aarhus
country: Denmark
facility: Aarhus Universitetshospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen (UKT)
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht (UMC Utrecht)
city: Warsaw
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka
state: Mazowieckie
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny,Centralny Szpital Kliniczny Ministerstwa Obronty Narodowej
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, KLINIKA PEDIATRII, HEMATOLOGII I ONKOLOGII
state: Pomorskie
city: Lodz
country: Poland
facility: Osrodek Pediatryczny im. DR J. Korczaka, Wojewodzkie Wielospecjalistyczne Centrum i Traumatologii im. M. Kopernika w Lodzi
city: Bratislava
country: Slovakia
facility: NUDCH (National Institute of Children's Diseases)
city: Kosice
country: Slovakia
facility: OKIA, s.r.o
city: Martin
country: Slovakia
facility: Klinika Deti a Dorastu - Odborne Ambulancie UNM a JLF UK Martin
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu Barcelona
state: Barcelona
city: Madrid
country: Spain
facility: University Hospital La Paz
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: