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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 Sep 2024 → 21 Jan 2026

Decision date (initial)

2024-08-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc

External identifiers

EU CT number

2022-502095-23-01

ClinicalTrials.gov

NCT05755035

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others

To demonstrate PK comparability of TAK-881 and HYQVIA at steady-state after subcutaneous (SC) administration in subjects aged ≥16 years with PIDD.

Secondary objectives 6

1. To assess infections in all subjects.
2. To assess healthcare resource utilization (HRU) for subjects using TAK-881/HYQVIA.
3. To evaluate PK, safety, tolerability and immunogenicity of TAK-881 in subjects aged ≥16 years with PIDD.
4. To characterize the PK of TAK-881 between subjects aged ≥16 years and subjects aged 2 to <16 years with PIDD.
5. To assess IgG trough levels and to evaluate safety, tolerability, and immunogenicity of TAK-881 in pediatric subjects aged 2 to <16 years with PIDD.
6. To evaluate infusion parameters at full dose for both TAK-881 and HYQVIA in all subjects.

Conditions and MedDRA coding

Primary Immunodeficiency Diseases

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subject 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 (Bousfiha et al., 2020, Tangye et al., 2021).
2. Subject is 2 years to <16 years at the time of signing the 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.
3. Subject 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 g/kg BW/4 weeks and a maximum dose equivalent to 1 g/kg BW/4 weeks. Over that period, the subject should have been on the same product of IGIV, HYQVIA, or cIGSC. A stable dose is defined as one that deviates less than ±25% 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 subjects with a 28-day treatment interval and of up to ±3 days for subjects with a 7, 14, or 21-day treatment interval are acceptable up to the first IP infusion.
4. Subject has a serum trough level of IgG >5 g/L at the following time points: a. At screening (sample taken prior to prestudy IgG infusion after signing the ICF) and b. Within 12 weeks prior to screening.
5. If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ a highly effective form of contraception for the duration of the study.
6. Subject 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.
7. The subject 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.
8. The subject 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 20

1. Subject 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 subjects with a history of hepatitis C infection who have a negative PCR test at screening are eligible.
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): a. Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5× the upper limit of normal (ULN) for the testing laboratory. b. Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤500/mm3).
3. Known history of chronic kidney disease, or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2 at screening.
4. Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site, at the discretion of the investigator.
5. Subject 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.
6. Subjects with a known systemic hypersensitivity to any of the excipients of TAK 881/HYQVIA in accordance with the IB/package insert/Summary of Product Characteristics (SmPC).
7. Known substance or prescription drug abuse within 12 months of screening.
8. Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07 g/L) associated with known anti-IgA antibodies and a history of hypersensitivity.
9. Subject has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
10. Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
11. Subject has a bleeding disorder or a platelet count less than 20,000/µL, or, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of IGSC therapy.
12. 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.
13. Live-attenuated viral vaccination within 12 weeks prior to screening.
14. History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device >2 years prior to screening are allowed.
15. Subject has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
16. Subject 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 subject at undue medical risk.
17. Subject has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening.
18. Subject is scheduled to participate in another clinical study involving an IP (except for subjects scheduled to enroll in a long-term follow-up study with TAK-881) or investigational device during the course of this study.
19. Subject is a family member or employee of the investigator or the investigator’s site staff.
20. If female, subject is pregnant or lactating at the time of screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is AUC0-τ,ss based on total IgG levels.

Secondary endpoints 5

1. Efficacy Endpoints 1. Annualized rate of all infections. 2. Annualized rate of ASBIs. 3. Annualized rate of episodes of fever. 4. Time to first ASBI. 5. Duration of infections.
2. Health Resource Utilization Endpoints 1. 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. 2. Days on antibiotics. 3. Number of hospitalizations, indication for the hospitalization (infection or other illnesses) and days hospitalized. 4. Number of acute physician visits due to infection or other illnesses.
3. Pharmacokinetic Endpoints 1. Pharmacokinetics at steady-state including Cmax, Tmax, t1/2, CL/F, Vz/F, and AUC0-τ,ss/week based on total IgG levels. 2. Trough level of total IgG. 3. Trough level of IgG subclasses. 4. Trough level of antigen-specific IgG antibodies (only for subjects ≥16 years).
4. Safety Endpoints • Occurrence of TEAEs. • Tolerability: occurrence of infusion withdrawals, interruptions, and infusion rate reductions due to TAK-881-related TEAEs. • Immunogenicity: occurrence of positive binding (defined as titer ≥1:160) and neutralizing antibodies to rHuPH20.
5. Note that clinically significant treatment-emergent changes in clinical laboratory measurements and vital signs will be recorded in the study database as TEAEs. Infusion Endpoints at Full Dose • Number of infusions per month. • Number of infusion sites (needle sticks) per month. • Number of infusion sites (needle sticks) per infusion. • Duration of infusions (minutes). • Monthly infusion time (minutes/month). • Maximum infusion rate per site (mL/hour/site). • Infusion volume per site (mL/site).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Andras Nagy

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 19

Locations

8 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 195 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications