Pharmacokinetic Comparability Study of TAK-881 and Human Normal Immunoglobulin in Chronic Inflammatory Demyelinating Polyradiculoneuropathy Patients
- Trial ID
- 2024-517450-95-00
- Protocol
- TAK-881-3003
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3, single-arm, multiple-dose trial is to demonstrate the **pharmacokinetic** (PK) comparability of TAK-881 and HYQVIA at steady-state following subcutaneous administration in patients with **Chronic Inflammatory Demyelinating Polyradiculoneuropathy** (CIDP). This objective is clinically relevant as it aims to establish whether TAK-881 can provide a similar PK profile to HYQVIA, which is crucial for ensuring therapeutic efficacy and safety in managing CIDP. No secondary objectives are specified for this study.
Participants
The clinical trial involves a total of **19 participants** diagnosed with **Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)**. The study population includes both male and female subjects, aged 18 years and older, who have a documented diagnosis of CIDP or possible CIDP, confirmed by a neurologist specializing in neuromuscular diseases. Participants have previously responded to immunoglobulin G (IgG) treatment and are on a stable pretrial treatment regimen with IGIV, cIGSC, or HYQVIA. The trial population was selected based on their ability to comply with trial procedures and requirements, as well as their informed consent. Participants are required to have an INCAT disability score between 0 and 7, with specific criteria for eligibility based on their score. Lifestyle considerations such as diet and physical activity are not specified, but participants with the potential to become pregnant must have a negative pregnancy test and agree to use effective contraception during the trial. The trial includes a vulnerable population, ensuring careful monitoring and ethical considerations throughout the study.
Plans and Procedures
The clinical trial is designed as a **Phase 3**, single-arm, multiple-dose, pharmacokinetic comparability study to evaluate the **pharmacokinetic** comparability of TAK-881 and HyQvia in adults with **chronic inflammatory demyelinating polyradiculoneuropathy** (CIDP). The trial will involve the administration of a **solution for infusion** containing **human normal immunoglobulin** and **hyaluronidase (human recombinant)** via the subcutaneous route. The trial is expected to commence recruitment on June 12, 2025, and conclude by May 30, 2030, with a maximum treatment period of 121 weeks for TAK-881 and 27 weeks for HyQvia.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of CIDP, and previous response to immunoglobulin treatment. The primary endpoint is the baseline-uncorrected area under the curve during the dosing interval at steady-state based on total IgG levels. Follow-up visits will be scheduled to monitor the pharmacokinetic parameters and safety of the investigational products. The end-of-study visit will assess the overall outcomes and any adverse events experienced by the participants.
The expected length of participant involvement will vary depending on the treatment arm, with TAK-881 participants involved for up to 121 weeks and HyQvia participants for up to 27 weeks. Conditions that may lead to early termination from the study include non-compliance with trial procedures, withdrawal of consent, or any adverse events that, in the opinion of the investigator, warrant discontinuation of the participant's involvement for safety reasons.
Treatment
The clinical trial involves the administration of **HyQvia**, a 100 mg/mL solution for infusion intended for subcutaneous use. This pharmaceutical product is composed of **human normal immunoglobulin**, a structurally diverse substance derived from blood. The solution is administered subcutaneously, with a maximum daily dose of 120 grams and a total dose not exceeding 1080 grams over a treatment period of 27 weeks. The administration is facilitated by devices such as the Qcore Sapphire Infusion Pump and the Koru 24G Subcutaneous Needle set, all of which have CE marks ensuring compliance with European safety standards. The infusion process may also involve the use of Sapphire Administration tubing and BD Plastipak Luer Lock Syringes for precise delivery.
Another treatment in the trial is **TAK-881**, a solution for infusion that combines **human normal immunoglobulin** and **hyaluronidase (human recombinant)**. This investigational product is also administered subcutaneously, with a maximum daily dose of 120 grams and a total dose limit of 7080 grams over a 121-week treatment period. The administration of TAK-881 utilizes similar devices as HyQvia, including the Qcore Sapphire Infusion Pump and the Koru 24G Subcutaneous Needle set, ensuring consistent delivery and patient safety. The inclusion of hyaluronidase facilitates the dispersion and absorption of the immunoglobulin, enhancing the therapeutic effect.
Both treatments are part of a Phase 3, single-arm, multiple-dose pharmacokinetic comparability trial aimed at evaluating the pharmacokinetic profiles of TAK-881 and HyQvia in adults with **Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)**. The trial's primary objective is to demonstrate the pharmacokinetic comparability of TAK-881 and HyQvia at steady-state following subcutaneous administration. Participant compliance is monitored through regular assessments and the use of standardized infusion devices, ensuring adherence to the dosing schedule and accurate data collection.
Efficacy
The efficacy of the investigational product in the clinical trial will be assessed primarily through the measurement of the baseline-uncorrected area under the curve during the dosing interval at steady-state (AUC0-τ,ss) based on total **IgG** levels. This parameter serves as the primary endpoint to evaluate the pharmacokinetic comparability between TAK-881 and HyQvia in adults with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). The trial is designed as a Phase 3, single-arm, multiple-dose study, focusing on the steady-state pharmacokinetics following subcutaneous administration.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The participant is willing and able to understand and fully comply with trial procedures and requirements, in the opinion of the investigator.
- The participant has provided informed consent (that is, in writing, documented via a signed and dated ICF) and any required privacy authorization before the initiation of any trial procedures.
- The participant is at least 18 years of age at the time of signing the ICF.
- The participant has a documented diagnosis of CIDP or possible CIDP, as confirmed by a neurologist specializing/experienced in neuromuscular diseases and consistent with the EAN/PNS 2021 criteria (Van den Bergh et al., 2021).
- The participant has responded to IgG treatment in the past (documented partial or complete resolution of neurological symptoms and deficits).
- The participant is on a stable, pretrial treatment with IGIV, cIGSC, or HYQVIA (also known as TAK-771 in Japan) within the dose range equivalent to a cumulative monthly IgG dose of 0.4 to 2.4 g/kg body weight (BW) (inclusive) administered for at least 12 weeks before screening. The dosing interval of IGIV treatment must be between 2 and 6 weeks (inclusive). The dosing interval must be weekly or biweekly for cIGSC dosing and ≤6 weeks for HYQVIA dosing. Prior to screening, variations in the dosing interval of up to ±7 days or monthly dose amount of up to ±20% between the participant’s consecutive pretrial IgG infusions are acceptable.
- The participant has an INCAT disability score between 0 and 7 (inclusive). Participants will be eligible if one of the below eligibility criteria are met: a. Screening INCAT disability score of between 3 and 7 inclusive. b. Screening INCAT disability score of 2 (both points are from lower extremities). c. Screening INCAT disability score of 2 (both points are not from lower extremities) AND has at least a score of 2 or greater documented in the medical record before screening. If a score was greater than 2 documented in the medical record before screening at least 2 points must be from lower extremities. d. Screening INCAT disability score of 0 or 1 AND has at least a score of 2 or greater (both from lower extremities) documented in the medical record before screening, at least 2 points must be from lower extremities.
- If a participant has the potential to become pregnant, they must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the trial and for at least 30 days after the last administration of IMP.
Exclusion Criteria
- Documented diagnosis of focal, multifocal, distal, or sensory CIDP, or possible focal, multifocal, distal, or sensory CIDP per the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2021 criteria (Van den Bergh et al., 2021).
- The participant has any neuropathy of other causes, including: a. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN), Charcot-Marie-Tooth (CMT) disease, and hereditary sensory and autonomic neuropathies (HSANs). b. Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy, lymphoma, amyloidosis. c. Multifocal motor neuropathy (MMN). d. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.
- The participant has any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or which may interfere with assessment of CIDP or outcome measures, including (but not limited to) multiple sclerosis, arthritis, stroke, Parkinson’s disease, and diabetic peripheral neuropathy. Note: Participants with clinically diagnosed diabetes mellitus who do not have diabetic peripheral neuropathy and who have adequate glycemic control with hemoglobin A1c [HbA1c] level of <7.5% at screening will be eligible for the trial, provided the electrodiagnostic criteria are consistent with the diagnosis of CIDP or possible CIDP consistent with the EFNS/PNS 2021 criteria and the participant agrees to maintain adequate glycemic control.
- The participant is required to take or has taken immunomodulatory/immunosuppressive agents (except IGIV, cIGSC, or fIGSC) that include but are not limited to specific complement inhibitors, rituximab, neonatal Fc receptor inhibitors (eg, efgartigimod), and chemotherapeutic drugs, within 6 months of screening. Participants on a long-term, stable dosing regimen of certain immunomodulatory agents (eg, hydroxychloroquine) for the treatment of non-CIDP conditions may be included in the trial.
- The participant is required to take or has taken long-term systemic corticosteroids defined as dosages >20 mg/day prednisone-equivalent for >30 days within 3 months of screening. Note: Participants using short-pulse dose corticosteroid course and oral daily corticosteroids ≤20 mg/day prednisone-equivalent are allowed.
- The participant has undergone plasma exchange within 3 months before screening.
- The participant has immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with a high titer of antibody to myelin-associated glycoprotein.
- The participant has immunoglobulin A (IgA) deficiency (IgA <0.07 g/L) associated with known anti-IgA antibodies and a history of hypersensitivity to human immunoglobulin treatment.
- The participant has a condition(s) which could alter protein catabolism and/or IgG use (eg, protein losing enteropathies, and nephrotic syndrome).
- The participant has a history or clinical manifestations of chronic kidney disease, or glomerular filtration rate of <30 mL/min/1.73 m2 estimated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey et al., 2009) at the time of screening.
- The participant has a history of malignancy with less than 2 years of complete remission before screening, or active malignancy requiring chemotherapy and/or radiotherapy. Note: Participants with adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stable prostate cancer not requiring treatment are eligible.
- The participant has congestive heart failure (New York Heart Association class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (defined as diastolic blood pressure >100 mm Hg and/or systolic blood pressure >160 mm Hg during the screening epoch confirmed on 2 measures >30 minutes apart).
- The participant has an acquired or inherited thrombophilic disorder, such as protein C deficiency, protein S deficiency, antithrombin deficiency, and primary antiphospholipid antibody syndrome.
- The participant has a history of deep vein thrombosis or arterial thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) within 12 months before screening.
- The participant has any 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 trial or place the participant at undue medical risk.
- Participant has a known history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC IGSC immunoglobulin, and/or immune serum globulin infusions.
- The participant has 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).
- Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
- The participant has a known history of positive result for 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 HIV Type 1 and Type 2. Note: Cured participants with a history of hepatitis C infection who have a negative PCR test at screening are eligible.
- The participant has clinically significant anemia that precludes repeated blood sampling during the trial, or hemoglobin level of <10.0 g/dL at the time of screening. Note: If in investigator judgement, the screening laboratory abnormalities are likely to be transient, then laboratory tests may be repeated. The investigator rationale is to be documented. Laboratory values can be retested once during screening as long as the participant can be evaluated for eligibility and can be enrolled within the allowed screening epoch.
- The participant has any of the following laboratory values at screening: a. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN). b. Platelet count <100,000 cells/μL. c. Absolute neutrophil count <1000 cells/μL. Note: If in investigator judgement, the screening laboratory abnormalities are likely to be transient, then laboratory tests may be repeated. The investigator rationale is to be documented. Laboratory values can be retested once during screening as long as the participant can be evaluated for eligibility and can be enrolled within the allowed screening epoch.
- If female, the participant is pregnant or lactating at the time of screening
- The participant has participated in another clinical trial involving an IMP or investigational device within 12 weeks or 5◦half-lives, whichever is longer, before enrollment (except for participants rolling over from the Japan study TAK-771-3002) or is scheduled to participate in another clinical trial involving an IMP or investigational device during the course of this trial.
- The participant is a trial site employee, an immediate family member (eg, spouse, parent, child, sibling), or is in a dependent relationship with a trial site employee who is involved in conduct of this trial, or may consent under duress.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Not Recruiting | 12 Jun 2025 | 4 |
 Denmark | Recruiting | 12 Jun 2025 | 7 |
 Germany | Recruiting | 12 Jun 2025 | 9 |
 Greece | Recruiting | 12 Jun 2025 | 3 |
 Italy | Recruiting | 12 Jun 2025 | 11 |
 Poland | Recruiting | 12 Jun 2025 | 7 |
 Spain | Not Yet Recruiting | 12 Jun 2025 | 3 |
 Sweden | Recruiting | 12 Jun 2025 | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
HyQvia 100 mg/mL solution for infusion for subcutaneous use | Comparator | SOLUTION FOR INFUSION FOR SUBCUTANEOUS USE | SUBCUTANEOUS | 120 | 27 | PRD3237752 |
TAK-881 | Test | SOLUTION FOR INFUSION | SUBCUTANEOUS | 120 | 121 | PRD10021986 |
HyQvia 100 mg/mL solution for infusion for subcutaneous use | Comparator | SOLUTION FOR INFUSION FOR SUBCUTANEOUS USE | SUBCUTANEOUS | 120 | 27 | PRD3237754 |