TAK-881 for Primary Immunodeficiency

Recruiting in Palo Alto (17 mi)

+1 other location

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Takeda

Disqualifiers: Serious medical condition, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main aim of this study is to learn if TAK-881 is safe and well tolerated during long-term use in adults and children with PIDD who are eligible and completed study TAK-881-3001 (NCT05755035). The participants will receive the first dose of TAK-881 immunoglobulin (IgG) infusion at the same dosage as the last dose administered in study TAK-881-3001 (NCT05755035). After the first TAK-881 infusion in study TAK-881-3002, the dosing interval (can be adjusted by participant/caregiver) and/or the dose of TAK-881 can be adjusted by the study doctor to every 2, 3 or 4 weeks at scheduled site visits. Participants will visit the clinic every 12 weeks until the End of Study (EOS) visit.

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.

What data supports the effectiveness of the treatment TAK-881 for primary immunodeficiency?

Research shows that using recombinant human hyaluronidase with immunoglobulin (a protein that helps fight infections) for primary immunodeficiency can reduce the number of infections and is generally safe and well-tolerated. This combination allows for easier and more effective delivery of the treatment under the skin, which can be done at home, making it more convenient for patients. ^{1 2 3 4 5}

Is TAK-881 safe for humans?

Research shows that TAK-881, also known as recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin, is generally safe for humans. Studies report that any side effects are usually mild to moderate and do not lead to stopping the treatment. ^{1 2 3 5 6}

How is the drug TAK-881 different from other treatments for primary immunodeficiency?

TAK-881 is unique because it combines human immunoglobulin (a protein that helps fight infections) with recombinant human hyaluronidase, which helps the immunoglobulin spread more easily under the skin. This allows for less frequent and fewer infusion sites compared to traditional treatments, making it more convenient for patients. ^{1 2 3 5 7}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

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

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])

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

Trial Timeline

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

Treatment Details

Interventions

• TAK-881 (Immunoglobulin Replacement Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Recombinant human hyaluronidase facilitated subcutaneous immunoglobulin treatment in pediatric patients with primary immunodeficiencies: long-term efficacy, safety and tolerability. [2022]

2. Italy 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. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

A case report of pregnancy in a patient with common variable immunodeficiency emphasizing the need for personalized immunoglobulin replacement. [2022]

6. Netherlands 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

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