TAK-881 for Primary Immunodeficiency

Recruiting at 5 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Disqualifiers: Serious medical condition, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if TAK-881 (Human normal immunoglobulin IgG combined with recombinant human hyaluronidase) is safe and well-tolerated for individuals with primary immunodeficiency (PIDD), a condition where the immune system malfunctions. Participants will receive TAK-881 through a regular infusion, which delivers medicine by slowly injecting it into the body. This trial is open to those who participated in an earlier study with TAK-881 and wish to continue. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study doctor to understand how your current medications might interact with the trial requirements.

Is there any evidence suggesting that TAK-881 is likely to be safe for humans?

Research has shown that TAK-881 was well-tolerated in earlier studies. In one study, healthy adults received a similar treatment and reported it as generally safe, with most experiencing no serious side effects.

Although this information comes from healthy participants, TAK-881 resembles treatments already approved for other uses, suggesting it might be safe for many people. However, individual experiences can vary. Always consult a doctor with any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for primary immunodeficiency, which often involve regular intravenous or subcutaneous immunoglobulin infusions, TAK-881 is delivered via a subcutaneous infusion using investigational needle sets. Researchers are particularly excited because TAK-881 may offer a more convenient dosing schedule—every 12 weeks—compared to the more frequent dosing required by current therapies. Additionally, TAK-881 targets the condition with a potentially improved safety profile by adjusting the dose and interval based on individual patient needs, which could enhance the overall treatment experience.

What evidence suggests that TAK-881 might be an effective treatment for primary immunodeficiency?

Research has shown that TAK-881, also known as hyaluronidase-facilitated subcutaneous immunoglobulin, is designed to help people with primary immunodeficiency (PIDD). This treatment combines immunoglobulin (IgG), a type of antibody, with an enzyme called rHuPH20, which helps the IgG spread more easily under the skin. Studies indicate that IgG replacement therapy, like TAK-881, is crucial for treating PIDD because it helps replace missing or low levels of antibodies. Participants in this trial will receive TAK-881, and previous users have experienced positive results in managing their condition. The treatment is generally well-tolerated and has a safety profile similar to other IgG therapies. ^{2 3 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for adults and children with Primary Immunodeficiency Diseases (PIDD) who completed the TAK-881-3001 study. Participants must agree to use contraception if applicable, have a negative pregnancy test if female of childbearing potential, and be willing to follow the study procedures.

Inclusion Criteria

Participant/Participant's parent(s)/legal guardian(s) is/are willing and able to comply with the requirements of the protocol

Participant must have completed Study TAK-881-3001 (NCT05755035)

Participant/Participant's parent(s)/legal guardian(s) has/have provided informed consent/assent (if applicable), including providing consent for use of the investigational medical device, prior to the initiation of any study procedures

Exclusion Criteria

Participant has a serious medical condition such that the participant's safety or medical care would be impacted by participation in this long-term follow-up study

New medical condition that developed during participation in Study TAK-881-3001 (NCT05755035), that, in the judgment of the investigator, could increase risk to the participant or interfere with the evaluation of TAK-881 and/or conduct of the study

Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to screening (with the exception of Study TAK-881-3001 [NCT05755035])

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Epoch 1)

Participants receive TAK-881 subcutaneous infusion every 12 weeks for a minimum of 6 months

6 months

Visits at Week 1, Week 13, and Week 25

Treatment (Epoch 2)

Participants with specific antibody titer levels continue receiving TAK-881 every 12 weeks for up to 2 years

2 years

Visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-881

Trial Overview

The safety and tolerance of long-term use of TAK-881 are being tested in this trial. Patients will start with the same dose they ended on in a previous study and can adjust dosage or interval between doses every 2, 3, or 4 weeks as directed by their doctor.

How Is the Trial Designed?

Group I: TAK-881 Experimental Treatment 2 Interventions

Epoch 1: Participants who completed study TAK-881-3001 (NCT05755035) and met eligibility criteria will receive TAK-881 subcutaneous (SC) infusion using investigational needle sets at the same dose and same treatment interval as at the last infusion in TAK-881-3001 (NCT05755035) at Week 1 and at Weeks 13 and Week 25 of study TAK-881-3002. Epoch 2: Participants with anti-rHuPH20 antibody titer \>=1:160 at any time point during Study TAK-881-3001 (NCT05755035) and/or Study TAK-881-3002 Epoch 1, will continue receiving TAK-881 every 12 weeks for up to Week 121. After the first TAK-881 infusion in study TAK-881-3002, the interval and/or the dose may be adjusted only at scheduled site visits at the investigator's discretion.

TAK-881 is already approved in Japan, Canada for the following indications:

Approved in Japan as TAK-881 for:

• Primary Immunodeficiency Diseases

Approved in Canada as TAK-881 for:

• Immunodeficiency disorders

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Baxalta Innovations GmbH, now part of Takeda

Collaborator

Trials

1

Recruited

40+

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

In a long-term study involving children with primary immunodeficiency diseases, recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (Ig) showed low rates of serious bacterial infections (0.08/patient-year) and minimal adverse reactions, indicating its safety and tolerability.

The study, which lasted up to 3.3 years, demonstrated that 97.2% of infusions required no changes due to adverse drug reactions, and a significant majority of patients preferred this subcutaneous method over traditional intravenous administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human hyaluronidase facilitated subcutaneous immunoglobulin treatment in pediatric patients with primary immunodeficiencies: long-term efficacy, safety and tolerability. Wasserman, RL., Melamed, I., Kobrynski, L., et al.[2022]

Both subcutaneous immunoglobulin (SCIG) and hyaluronidase-facilitated SCIG (fSCIG) effectively maintained serum immunoglobulin G (IgG) levels above the protective threshold of 7 g/L in patients with primary immunodeficiency diseases after switching from intravenous immunoglobulin (IVIG).

The study found that while mean IgG trough values were higher in obese patients and lower in pediatric patients compared to adults, these differences (up to 22%) do not necessitate dose adjustments based solely on BMI or age; instead, dosing should be tailored based on previous IVIG doses and individual monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Body Mass and Age on the Pharmacokinetics of Subcutaneous or Hyaluronidase-facilitated Subcutaneous Immunoglobulin G in Primary Immunodeficiency Diseases. Li, Z., Follman, K., Freshwater, E., et al.[2023]

Subcutaneous immunoglobulin therapy, enhanced with recombinant human hyaluronidase, allows for larger infusion volumes and faster administration rates, making it comparable to intravenous therapy while improving patient comfort.

A phase III clinical trial demonstrated that this enzyme-enhanced subcutaneous method is well tolerated, potentially increasing patient adherence and quality of life compared to traditional intravenous immunoglobulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in gammaglobulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. Wasserman, RL.[2021]

A 31-year-old woman with common variable immunodeficiency (CVID) successfully switched from intravenous immunoglobulin (IVIg) to subcutaneous immunoglobulin (SCIg) administration facilitated by recombinant human hyaluronidase during her pregnancy, allowing for effective treatment every 3-4 weeks.

The treatment was well tolerated and maintained sufficient immunoglobulin G (IgG) levels for both the mother and her newborn, highlighting the importance of patient preference and medical needs in choosing immunoglobulin administration methods during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case report of pregnancy in a patient with common variable immunodeficiency emphasizing the need for personalized immunoglobulin replacement. Więsik-Szewczyk, E., Jahnz-Różyk, K.[2022]

Recombinant human hyaluronidase (rHuPH20) enhances the absorption and distribution of subcutaneous immunoglobulin G (SCIG) in patients with primary immunodeficiency diseases (PIDD), allowing for fewer and less frequent infusions.

Clinical studies indicate that SCIG facilitated with rHuPH20 (IGHy) is effective in preventing infections and is well-tolerated, significantly reducing the number of infusion sites needed compared to traditional SCIG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin infusion in primary immunodeficiency diseases. Wasserman, RL.[2018]

In a study of 30 patients with immunodeficiency diseases, the use of recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG; HyQvia) significantly reduced the rate of infections compared to pre-treatment levels, indicating its efficacy in managing these conditions.

The treatment was found to be safe and well-tolerated, with only mild to moderate adverse events reported, none of which led to treatment discontinuation, allowing patients to self-administer the therapy at home.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency diseases: real-life data from a monocentric experience. Angelotti, F., Capecchi, R., Giannini, D., et al.[2021]

Subcutaneous infusions of IgG combined with recombinant human hyaluronidase (rHuPH20) were found to be safe and effective for treating primary immunodeficiency diseases (PIDD) in 83 subjects over a long-term period, with a low rate of adverse events (AEs) and stable infection rates.

The study showed that local adverse events decreased significantly over time, from 3.68 per subject-year in the first year to about 1.50 per subject-year after 30 months, indicating improved tolerance to the treatment with continued use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. Wasserman, RL., Melamed, I., Stein, MR., et al.[2018]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05755035

NCT05755035 | A Study About How TAK-881 is Processed ...

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 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10739571/

A Phase 1 Open-Label Study to Assess the Tolerability ...

Hyaluronidase-facilitated subcutaneous immunoglobulin 20% (fSCIG 20%, also known as TAK-881) is an infusion of IgG 20% and rHuPH20. The ratio of ...

3.

synapse.patsnap.com

synapse.patsnap.com/drug/e3f5a214cdb64f0aa286f7b4b04160ac

Human normal immunoglobulin(Takeda) - Drug Targets ...

INDICATIONS FOR HYQVIA HYQVIA is indicated for the treatment of primary immunodeficiency (PI) in adults and pediatric patients two years of age and older and ...

4.

fda.gov

fda.gov/media/168253/download

April 7, 2023 Clinical Review Memo - HYQVIA

This choice of primary efficacy outcome is consistent with the FDA guidance document “Safety, Efficacy, and Pharmacokinetic Studies to Support ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4928364/

Hyaluronidase facilitated subcutaneous immunoglobulin in ...

Immunoglobulin (Ig)-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05755035

NCT05755035 | A Study About How TAK-881 is Processed ...

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 ...

7.

cda-amc.ca

cda-amc.ca/sites/default/files/DRR/2022/ST0695-HyQvia-meta.pdf

Normal Immunoglobulin (Human) 10% and Recombinant ...

sufficient data to supplement the safety outcomes data ... recombinant human hyaluronidase; IVIg = intravenous immunoglobulin; PID = primary immunodeficiency ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00782106

NCT00782106 | Study to Determine the Dose of ...

The purpose of the study is to determine the feasibility of infusing a full 4-week dose of Immune Globulin Intravenous (Human), 10% in a single subcutaneous ...