TAK-881 for Primary Immunodeficiency
Recruiting in Palo Alto (17 mi)
+40 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Takeda
Must be taking: Immunoglobulin
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Hepatitis, HIV, Kidney disease, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the treatment HyQvia for primary immunodeficiency?
Research shows that HyQvia, which combines human immunoglobulin with recombinant human hyaluronidase, is effective in reducing infection rates in patients with primary immunodeficiency. It is well-tolerated, with mostly mild to moderate side effects, and allows for less frequent dosing compared to other treatments, making it convenient for home use.
12345Is TAK-881 (HyQvia) safe for humans?
TAK-881, also known as HyQvia, has been shown to be generally safe for humans, with most adverse events being mild to moderate, such as local infusion site reactions. It is well tolerated and offers a new method for delivering immunoglobulin therapy, with a safety profile comparable to traditional intravenous methods.
12367How is the drug TAK-881 different from other treatments for primary immunodeficiency?
TAK-881 (HyQvia) is unique because it combines human immunoglobulin with recombinant human hyaluronidase, allowing larger doses to be given less frequently through a single subcutaneous injection. This method reduces the frequency of infusions compared to other subcutaneous treatments and is generally preferred by patients over intravenous administration due to its convenience and lower rate of systemic side effects.
12378Eligibility Criteria
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.
+7 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Single Arm Treatment Epoch: TAK-881Experimental Treatment1 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 Treatment2 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 Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California Irvine Medical CenterIrvine, CA
Allergy and Asthma Clinical ResearchWalnut Creek, CA
National Jewish Medical And Research CenterDenver, CO
University of South FloridaSaint Petersburg, FL
More Trial Locations
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Who Is Running the Clinical Trial?
TakedaLead Sponsor
Takeda Development Center Americas, Inc.Industry Sponsor
References
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]Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency patients. We collected retrospective data from 30 patients with primary and secondary immunodeficiency diseases in therapy with fSCIG from September 2014 to December 2019. We evaluated the efficacy of the therapy, taking into account serum IgG values during follow-up and the number of annual infectious events and serious bacterial infections reported by patients. Safety was assessed on the basis of the number and intensity of adverse events (AEs) and local reactions reported. Our real-life data suggest that long-term repeated self-administration of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulins results in a reduced rate of infectious events if compared to the pre-treatment rate. Both AEs and local reactions are mild to moderate and were never reasons for treatment discontinuation. Therapy with HyQvia shows prolonged efficacy and good tolerability; these aspects, together with the possibility of self-administration at home, minimize the impact the illness has on patients.
Clinical Practice Experience with HyQvia in Adults Using Alternative Dosing Regimens and Pediatric Patients: A Retrospective Study. [2022]HyQvia (Immune Globulin Infusion 10% [Human] with Recombinant Human Hyaluronidase) was developed to combine the advantages of intravenous and subcutaneous immune globulin (SCIG), allowing administration of larger volumes at a single subcutaneous site with less frequent dosing when compared to other SCIG products. Current US prescribing guidelines for HyQvia are limited to adults and do not encompass the flexibility required to achieve success in all patients with primary immunodeficiency (PID).
Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders. [2016]Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.
Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Subcutaneous immunoglobulin is one of the standard treatments for hypogammaglobulinemia in primary immunodeficiencies (PID) worldwide. In Japan, IgPro20 (Hizentra® ; l-proline-stabilized 20% human subcutaneous immunoglobulin) is approved for agammaglobulinemia or hypogammaglobulinemia due to PID or secondary immunodeficiency (SID); however, its safety and effectiveness has not previously been assessed in a real-world setting.
Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. [2022]Subcutaneous immunoglobulin (IGSC) replacement therapy for primary immunodeficiency (PI) is equally efficacious to intravenous immunoglobulin (IGIV), induces fewer systemic reactions, and may be self-infused. Limited SC infusion volumes and reduced bioavailability, however, necessitate multiple infusion sites, more frequent treatment, and dose adjustment to achieve pharmacokinetic equivalence. Recombinant human hyaluronidase (rHuPH20) increases SC tissue permeability and facilitates dispersion and absorption, enabling administration of monthly doses in one site.
Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. [2020]Aim: This prospective, Phase III study assessed the pharmacokinetics (PK), safety and tolerability of immune globulin subcutaneous, human - klhw 20% solution (IGSC-C 20%) in participants with primary humoral immunodeficiency (PI), compared with immune globulin injection (human), 10% caprylate/chromatography purified (IGIV-C 10%). Patients & methods: About 53 participants enrolled. Total 44 received IGIV-C 10% in the run-in phase and then entered the IV phase (with an additional nine who were already receiving IGIV-C 10% and entered the IV phase directly) for steady-state IV PK assessments. Total 49 entered the SC phase (weekly doses of IGSC-C 20% for ∼24 weeks). The PK profiles of IGIV-C 10% and IGSC-C 20% and their safety and tolerability parameters were compared. Results: At a dose adjustment factor of 1.37, IGSC-C 20% provided comparable (noninferior and bioequivalent) overall total immunoglobulin G exposure to IGIV-C 10% over an equal time interval. About 33 participants reported 79 adverse events during run-in + IV phases; 41 participants reported 141 adverse events during the SC phase, with most being local infusion site reactions. The majority of infusion site reactions were mild to moderate in severity. Conclusion: IGSC-C 20% was bioequivalent to IGIV-C 10% and was well tolerated, with a safety profile comparable with IGIV-C 10%, in this study. Trial registration: ClinicalTrials.gov identifier: NCT02604810.
Cost-minimization analysis of IgPro20, a subcutaneous immunoglobulin, in Japanese patients with primary immunodeficiency. [2018]IgPro20, Hizentra(®) an L-proline-stabilized 20% human subcutaneous immunoglobulin (SCIG), has been shown in a Phase III pivotal study to be well tolerated and efficacious in adult and pediatric Japanese patients with primary immunodeficiency. Economic aspects of SCIG treatment in comparison with previous intravenous immunoglobulin (IVIG) therapy were analyzed in this Phase III study in Japan.
Transitioning subcutaneous immunoglobulin 20% therapies in patients with primary and secondary immunodeficiencies: Canadian real-world study. [2023]Real-world data on transitioning to Immune Globulin Subcutaneous (Human) 20% solution (Ig20Gly) are limited. This study aimed to assess infusion parameters and experience of patients with primary (PID) or secondary immunodeficiencies (SID) transitioning to Ig20Gly in clinical practice in Canada.