Primary Immunodeficiency Diseases (PID)
Conditions
Keywords
Immunoglobulin replacement therapy; facilitated subcutaneous, Immunoglobulin; primary immunodeficiency disease
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).
Interventions
Sponsors
Takeda
Takeda Development Center Americas, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study consists of crossover randomized epoch (participants aged \>=16 years) and single arm epoch (participants aged 2 to \<16 years).
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve Over One Dosing Interval at Steady-State (AUC0-tau;ss) of Total IgG Levels With TAK-881 and HYQVIA Treatment in Participants >= 16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | AUC0-tau;ss was defined as the area under the curve over one dosing interval at steady-state. The AUC0-tau;ss was calculated during the dosing interval after the last dose in each crossover epoch by the non-compartmental analysis (NCA) based on total IgG levels for TAK-881 and HYQVIA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Annualized Rate of All Infections | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Mean annualized rates and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale. |
| Mean Annualized Rate of Acute Serious Bacterial Infections (ASBIs) | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Mean annualized rates of ASBIs and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale. |
| Mean Annualized Rate of Fever Episodes | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Mean annualized rates of fever episodes and corresponding two-sided 95% CIs were reported for TAK-881 and HYQVIA and were analyzed using a generalized linear model. The response distribution was assumed to be Poisson with a logarithmic link function. The model included the natural logarithm of the length of the observational period in years as an offset to account for potential differences in lengths of the observational periods per participant. Results were back transformed from the logarithmic scale. |
| Time to First ASBI | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | The time to first ASBI was defined as the time between the first investigational product (IP) administration (referring to the first ramp-up dose, if ramp-up is applicable, or to the first full dose at Week 1, if ramp-up is not applicable) and the first occurrence of the ASBI. The median time to first ASBI was reported. |
| Duration of Infections | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | The median duration of infections was reported. Only participants with an infection are included here. |
| Number of Days Not Able to go to School, Work, Daycare, or to Perform Normal Daily Activities Due to Infections and/or Their Treatment, or Other Illnesses | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | The mean number of days with daily activity impairment per participant-year was reported. |
| Number of Days on Antibiotics Due to Treatment of Infection | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Days on antibiotics were calculated as the total number of calendar days during which at least one respective antibiotic was administered due to treatment of infection. Data was collected for administration via oral or parenteral and all routes. The mean number of days on antibiotics per participant-year was reported. |
| Number of Participants Hospitalized Due to Infection or Other Illnesses | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Number of participants hospitalized due to infection or other illnesses were reported. |
| Number of Days of Hospitalization Due to Infections or Other Illnesses | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | The number of days of hospitalization due to infection per participant-year was reported. |
| Number of Participants With Acute Physician Visits Due to Infection or Other Illnesses | Single arm treatment: Up to 27 weeks; Crossover treatment: Up to 51 weeks | Number of participants with acute physician visits due to infection or other illnesses was reported. |
| Maximum Concentration (Cmax) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | Cmax of total IgG with TAK-881 and HYQVIA at steady-state was reported. |
| Time to Maximum Concentration (Tmax) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | Tmax of total IgG with TAK-881 and HYQVIA at steady-state was reported. |
| Terminal Half-life (t1/2) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | t1/2 of total IgG with TAK-881 and HYQVIA at steady-state was reported. t1/2 was estimated by noncompartmental analysis from the terminal elimination-rate constant derived from the slope of the log-linear decline in total IgG concentrations during the terminal phase of the concentration-time profile. The estimated t1/2 may exceed the 21- or 28-day PK sampling interval. The PK assessment period did not extend beyond the protocol-defined 21-day or 28-day interval. |
| Apparent Clearance (CL/F) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | CL/F of total IgG with TAK-881 and HYQVIA at steady-state was reported. |
| Apparent Volume of Distribution (Vz/F) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | Vz/F of total IgG with TAK-881 and HYQVIA at steady-state was reported. |
| AUC0-tau;ss Per Week (AUC0-tau;ss/Week) of Total IgG With TAK-881 and HYQVIA at Steady-State in Participants >=16 Years | During the dosing interval of 8th dose (3-week) or 6th dose (4-week): 3-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21 days (post-infusion); 4-week dosing - Day 1 (pre & post-infusion), 24,48,72 hours, 7,14,21,28 days (post-infusion) | AUC0-tau;ss/week of total IgG with TAK-881 and HYQVIA at steady-state was reported. |
| Trough Level of Total IgG | Single arm treatment: pre-infusion at Week 25 during the 4-week dosing; Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen | The trough level of total IgG was reported. Total IgG trough levels were analyzed using the last trough level per participants (at the end of the last dosing interval). |
| Trough Level of IgG Subclasses | Single arm treatment: pre-infusion at Week 21 during the 4-week dosing; Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen | The trough level of IgG subclasses was reported. Trough levels of IgG subclasses were analyzed using the last trough level per participants (at the end of the last dosing interval). |
| Trough Level of Antigen Specific IgG Antibodies in Participants >=16 Years | Crossover treatment: pre-infusion at Weeks 25, 49, corresponding to 21 days after the last dose for 3-week dosing and 28 days after the last dose for 4-week regimen | The trough level of antigen specific IgG antibodies (Clostridium tetani toxoid, Haemophilus influenzae, and hepatitis B) was reported. Antigen-specific IgG antibodies were analyzed using the last trough level per participant in each crossover epoch (at the end of the last dosing interval). |
| Simulated AUC0-tau;ss of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. AUC0-tau;ss was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% predicted interval (PI) derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated Cmax of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Cmax was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated Tmax of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Tmax was estimated for the simulated PK profiles and summarized by age group. Median and full range derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated t1/2 of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. t1/2 was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated CL/F of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. CL/F was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated Vz/F of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. Vz/F was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Simulated AUC0-tau;ss/Week of TAK-881 at Steady-State | During the dosing interval of 6th dose (4-week): From Day 1 (pre and post infusion) every day up to 4 weeks | Sparse PK sampling was conducted for participants aged 2 to \<16 years. A population PK model integrating PK data from participants aged 2 to \<16 years and participants aged \>=16 years was developed. Population PK simulations were performed using virtual pediatric and adult populations constructed from age- and sex-specific body weight distributions, ensuring that the simulations were representative of the target PIDD population. AUC0-tau;ss/week was estimated for the simulated PK profiles and summarized by age group. Geometric mean and 90% PI derived from the simulation (N = 3000 per age group) at the observed median of average body weight adjusted TAK-881 full-dose per participant for every-4-week dosing frequency were reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From the start of study drug administration, up to 27 weeks (Single arm treatment) and up to 51 weeks (Crossover treatment) | An adverse event (AE) was any untoward medical occurrence in a clinical study subject, temporally associated with the use of the study intervention, whether or not the occurrence is considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study intervention. A TEAE was defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product. |
| Number of Participants With Infusion Withdrawals, Interruptions, or Infusion Rate Reductions Due to TAK-881-related TEAEs | From the start of study drug administration, up to 23 weeks (Single arm treatment) and up to 48 weeks (Crossover treatment) | Number of participants with infusion withdrawals, interruptions, or infusion rate reductions due to TAK-881-related TEAEs were reported. |
| Number of Participants With Positive Binding Antibodies (Titer Greater Than and Equal to [>=] 1:160) and Positive Neutralizing Antibodies to Recombinant Human Hyaluronidase PH20 (rHuPH20) | From the start of study drug administration, up to 23 weeks (Single arm treatment) and up to 51 weeks (Crossover treatment) | Participants were considered "Positive" if corresponding titer is \>=1:160 and were considered "Negative" if no anti-drug antibodies (ADA) is quantified (negative assay result) or the corresponding titer is \<1:160. |
| Number of Infusions Per Month at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | Number of infusion per month at full dose was calculated as the total number of full dose infusions divided by the total time in months on treatment. A single aggregate value was therefore presented; a measure of dispersion was not applicable. |
| Duration of Infusions Per Participant at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | The sum of the following: 1) Stop time of rHuPH20 - start time of rHuPH20; 2) Sum of all individual IgG duration steps; 3) Start time of IgG - Stop time of rHuPH20, 4) Duration of all IgG interruptions independent of the reason for interruption. For each participant, the average infusion duration was calculated; participant-level averages were then summarized using median and full range. |
| Monthly Infusion Time Per Participant at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | Monthly infusion time per participant at full dose was calculated as the total duration of full dose infusions per treatment divided by the total time in months on the respective treatment. For each participant, the average monthly infusion time was calculated; participant-level averages were then summarized using median and full range. |
| Number of Infusion Sites (Needle Sticks) Per Infusion at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | Number of infusion sites per infusion at full dose was calculated as the total number of full dose infusion sites divided by the total number of full dose infusions with an available infusion site. A single aggregate value was therefore presented; a measure of dispersion was not applicable. |
| Number of Infusion Sites (Needle Sticks) Per Month at Full Dose With Both TAK-881 and HYQVIA in All Participant | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | Number of infusion sites per month at full dose was calculated as the total number of full dose infusion sites divided by the total time in months on treatment. A single aggregate value was therefore presented; a measure of dispersion was not applicable. |
| Maximum Tolerated Infusion Rate Per Site at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | The maximum tolerated infusion rate at full dose was reported for rHuPH20 and IgG. |
| Infusion Volume Per Site Per Participant at Full Dose With Both TAK-881 and HYQVIA | Single arm treatment: Up to 20 weeks; Crossover treatment: Up to 45 weeks | Infusion volume per site at full dose was reported for rHuPH20 and IgG. Infusion volume was measured in milliliters (mL), and infusion volume per site was reported in terms of mL per site per participant. For each participant, the average infusion volume per site was calculated; participant-level averages were then summarized using median and full range. |
Countries
Czechia, Denmark, Germany, Netherlands, Poland, Slovakia, Spain, United States
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants with primary immunodeficiency diseases (PIDD) took part in the study across 26 investigative sites in Czech Republic, Denmark, Spain, Greece, Netherlands, Poland, Slovakia, and United States from 24 October 2023 to 20 January 2026. Participants previously treated with IGIV or HYQVIA maintained their prestudy 3- or 4-week dosing interval. For participants previously treated with conventional IGSC, the 3- or 4-week dosing interval was selected by the investigator at screening.
Pre-assignment details
Participants aged greater than or equal to \[\>=\]16 years were randomized at a 1:1 ratio in the crossover part to one of the following treatment sequences: TAK-881 followed by HYQVIA (Sequence 1 \[AB\]) or HYQVIA followed by TAK-881 (Sequence 2 \[BA\]). Pediatric participants aged 2 to less than \[\<\] 16 years received treatment with the study drug (TAK-881 only) in a single-arm part.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 8.2 years STANDARD_DEVIATION 4.24 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 41 | 0 / 38 |
| other Total, other adverse events | 21 / 22 | 31 / 41 | 31 / 38 |
| serious Total, serious adverse events | 3 / 22 | 1 / 41 | 3 / 38 |
Outcome results
None listed