TAK-881 for Primary Immunodeficiency

Not currently recruiting at 46 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Takeda

Must be taking: Immunoglobulin

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Hepatitis, HIV, Kidney disease, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 27-51 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAK-881 (Human normal immunoglobulin IgG combined with recombinant human hyaluronidase) for individuals with primary immunodeficiency, a condition that weakens the body's ability to fight infections due to poor antibody formation. Researchers compare TAK-881 to an existing treatment, HYQVIA, to assess safety and effectiveness. The trial involves either alternating between TAK-881 and HYQVIA for adults or maintaining TAK-881 for children, with regular check-ups every few weeks. Individuals on a stable dose of immunoglobulin treatments who require regular injections might be suitable for this study. As a Phase 2, Phase 3 trial, this study is crucial for evaluating TAK-881's effectiveness and represents the final step before potential FDA approval, offering participants a chance to contribute to advancing treatment options.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it does require that you have been on a stable dose of immunoglobulin treatment before joining. If you are taking immunosuppressants or have had a live-attenuated viral vaccination recently, you may not be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TAK-881 is generally safe for healthy adults, with most people not experiencing serious side effects. Ongoing studies are examining its safety for individuals with primary immunodeficiency diseases (PIDD).

HYQVIA, another treatment in the study, has already received FDA approval for treating primary immunodeficiency. It has been tested for safety in adults and children aged 2 and older. The most common side effects are mild, such as swelling or redness at the injection site.

In summary, both TAK-881 and HYQVIA are generally considered safe based on current research and approvals. However, individual experiences may vary, and ongoing studies will provide more detailed information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TAK-881 because it offers a potentially more convenient option for people with primary immunodeficiency, who traditionally rely on regular intravenous immunoglobulin (IGIV) or subcutaneous immunoglobulin (cIGSC) treatments. Unlike these standard therapies, TAK-881 is being explored for its ability to provide effective immune support with fewer infusions, which could improve patients' quality of life by reducing treatment frequency. Additionally, TAK-881's unique formulation might offer enhanced protection and stability, which could lead to better overall management of the condition. By simplifying the treatment process while maintaining efficacy, TAK-881 could represent a significant advancement in the care of individuals with primary immunodeficiency.

What evidence suggests that this trial's treatments could be effective for primary immunodeficiency?

Research has shown that both TAK-881 and HYQVIA are promising treatments for primary immunodeficiency. In this trial, participants will receive these treatments in different sequences. TAK-881, also known as fSCIG 20%, has proven effective and safe in several studies, with patients tolerating it well. Similarly, HYQVIA is already used to treat primary immunodeficiency and has proven safe and effective for both adults and children. Studies indicate that HYQVIA allows for longer intervals between treatments, offering more convenience without losing effectiveness. Both treatments help patients manage their condition by strengthening the immune system. ^{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 children and adults with Primary Immunodeficiency Diseases (PIDD) who need regular immune globulin treatments. Participants aged 2-15 will only receive TAK-881, while those 16+ may also get HYQVIA. They must have been on a stable dose of immunoglobulin therapy prior to the study and be willing to follow the study procedures.

Inclusion Criteria

I have had an IgG level over 5 g/L before my last IVIG or HYQVIA treatment.

I have a diagnosed immune system disorder that affects my body's ability to produce antibodies, requiring me to receive immunoglobulin (IgG) replacement.

I've been on regular IVIG or HYQVIA treatment every 3-4 weeks for at least 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-4 weeks

Ramp-up

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

1-4 weeks

Treatment

Participants receive TAK-881/HYQVIA or HYQVIA/TAK-881 with the same dose and dosing interval of immunoglobulin

27-51 weeks

Clinic visits every 3 or 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HYQVIA
• TAK-881

Trial Overview The trial is testing how TAK-881, given under the skin, compares to HYQVIA in treating PIDD. It looks at how the body processes these drugs, their safety, tolerability, and potential immune response over up to 51 weeks for adults and up to 27 weeks for kids.

How Is the Trial Designed?

Group I: Single Arm Treatment Epoch: TAK-881 Experimental Treatment 1 Intervention

Pediatric participants aged 2 to \<16 years will receive 6 or 8 infusions at full doses of TAK-881. The first full dose of TAK-881, will be administered either 2 weeks after the second ramp-up dose (applicable for participants pretreated with IGIV or cIGSC) or 3 or 4 weeks after the last infusion of their prestudy IgG treatment (applicable for participants pre-treated with HYQVIA).

Group II: Randomized Crossover Treatment Epoch: TAK-881 followed by HYQVIA (Sequence 1) Experimental Treatment 2 Interventions

Participants aged \>=16 years will receive 6 or 8 infusions at full doses of TAK-881 followed by HYQVIA in sequence 1. The first full dose of TAK-881 will be administered either 2 weeks after the second ramp-up dose (applicable for participants pretreated with IGIV or cIGSC) or 3 or 4 weeks after the last infusion of their pre study immunoglobulin G (IgG) treatment (applicable for participants pre-treated with HYQVIA).

Group III: Randomized Crossover Treatment Epoch: HYQVIA followed by TAK-881 (Sequence 2) Experimental Treatment 2 Interventions

Participants aged \>=16 years will receive 6 or 8 infusions at full doses of HYQVIA followed by TAK-881 in Sequence 2. The first full dose of HYQVIA will be administered either 2 weeks after the second ramp-up dose (applicable for participants pretreated with IGIV or cIGSC) or 3 or 4 weeks after the last infusion of their pre study IgG treatment (applicable for participants pre-treated with HYQVIA).

HYQVIA is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as HyQvia for:

• Primary immunodeficiency diseases
• Chronic inflammatory demyelinating polyradiculoneuropathy

Approved in United States as HyQvia for:

• Primary immunodeficiency diseases

Approved in Canada as HyQvia for:

• Primary immunodeficiency diseases
• Immunodeficiency disorders in adolescents and children

Approved in Japan as HyQvia for:

• Primary immunodeficiency diseases
• Chronic inflammatory demyelinating polyradiculoneuropathy

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

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Published Research Related to This Trial

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(&#174;)) in immunodeficiency diseases: real-life data from a monocentric experience. Angelotti, F., Capecchi, R., Giannini, D., et al.[2021]

A retrospective study involving 38 patients with primary immunodeficiency (PID) showed that HyQvia can be administered with flexible regimens outside of standard guidelines, including shorter ramp-up periods and using multiple infusion sites, without increasing adverse events.

In pediatric patients, HyQvia demonstrated good tolerability, with 4 out of 5 children experiencing no adverse events, suggesting that this treatment can be effectively tailored for younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Practice Experience with HyQvia in Adults Using Alternative Dosing Regimens and Pediatric Patients: A Retrospective Study. Wasserman, RL.[2022]

In a Phase III study involving 24 Japanese patients with primary immunodeficiency, switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (IgPro20) significantly improved quality of life, with Life Quality Index scores increasing from 45.1 to 71.9, indicating a large effect size.

The transition to IgPro20 also led to a 60% reduction in productivity loss and increased the number of patients able to maintain work and household duties, highlighting the economic benefits and reduced hospital visits associated with this home-based treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency. Igarashi, A., Kanegane, H., Kobayashi, M., et al.[2018]

In a real-world study of 85 patients receiving IgPro20 for hypogammaglobulinemia, 45.9% experienced adverse events, with injection site reactions being the most common, but the treatment was generally considered safe.

The effectiveness of IgPro20 was demonstrated by a reduction in infection rates from 0.54 per patient before treatment to 0.39 during treatment, indicating it helps protect against infections in patients with primary and secondary immunodeficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan. Imai, K., Ishii, T., Nonoyama, S., et al.[2023]

HyQvia® (IGHy), a combination of recombinant human hyaluronidase and human immunoglobulin, allows for subcutaneous administration of immunoglobulin therapy with reduced frequency and fewer infusion reactions compared to traditional intravenous methods, based on a study of 87 patients with primary immunodeficiency disorders.

The study found that IGHy maintained similar IgG levels and infection rates as intravenous immunoglobulin, while showing a lower rate of systemic adverse events and higher patient preference for the subcutaneous method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders. Sanford, M.[2016]

The study found that the immune globulin subcutaneous, human - klhw 20% solution (IGSC-C 20%) is bioequivalent to the immune globulin injection (IGIV-C 10%), providing similar levels of immunoglobulin G exposure over time, based on a Phase III trial with 53 participants.

IGSC-C 20% was well tolerated, with most adverse events being mild to moderate local infusion site reactions, indicating a safety profile comparable to IGIV-C 10%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. Sleasman, JW., Lumry, WR., Hussain, I., et al.[2020]

In a study of 125 patients with primary or secondary immunodeficiencies transitioning to Immune Globulin Subcutaneous (Human) 20% solution (Ig20Gly), the infusion was well-tolerated with most patients reporting satisfaction and a desire to continue treatment after 12 months.

The study found that headaches and infusion-site reactions were the most common adverse events, but overall, patients experienced a positive quality of life and effective administration of Ig20Gly, whether via pump or manual methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitioning subcutaneous immunoglobulin 20% therapies in patients with primary and secondary immunodeficiencies: Canadian real-world study. Keith, PK., Cowan, J., Kanani, A., et al.[2023]

In a phase III study involving 87 patients with primary immunodeficiency, rHuPH20-facilitated subcutaneous immunoglobulin (IGHy) was found to be effective and pharmacokinetically equivalent to intravenous immunoglobulin (IGIV), allowing for administration at longer intervals with fewer infusion sites.

Patients receiving IGHy experienced significantly fewer systemic reactions (8.3%) compared to those on IGIV (25.0%), indicating improved tolerability while maintaining similar efficacy in preventing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. Wasserman, RL., Melamed, I., Stein, MR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333520/

Long-Term Safety of Facilitated Subcutaneous ... Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

2. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213219825005367

Facilitated Subcutaneous Immunoglobulin 10% Safety ... This review provides an overview of data published to date relating to the safety and tolerability of fSCIG 10% for the treatment of primary ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03277313

Study Details | NCT03277313 | Efficacy, Safety, Tolerability ... The purpose of the study is to acquire additional data on efficacy, safety, tolerability, immunogenicity, pharmacokinetic (PK) and other parameters of HYQVIA ...

5. hyqviahcp.com hyqviahcp.com/primary-immunodeficiency/dosing-administration

HyQvia Dosing & Administration | SCIG Infusion Time for PI HyQvia delivers long-lasting, monthly protection for your patients with PI who want a little more time between infusions.

6. hyqvia.com hyqvia.com/primary-immunodeficiency/effectiveness-and-safety

HyQvia Side Effects & Safety Considerations HyQvia is a liquid medicine that is given under the skin (subcutaneously) to treat primary immunodeficiency (PI) in people 2 years and older.

7. ema.europa.eu ema.europa.eu/en/documents/product-information/hyqvia-epar-product-information_en.pdf

HyQvia, INN-human normal immunoglobulin (SCIg) - EMA The 2 components of the medicinal product must be administered sequentially through the same subcutaneous needle beginning with the rHuPH20 followed by IG 10%.

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

A Phase 1 Open-Label Study to Assess the Tolerability ... fSCIG 20% was well-tolerated with a favorable safety profile in healthy adults. Future studies will evaluate fSCIG 20% in primary immunodeficiency diseases.