A Phase 3, Single-Arm, Multiple-Dose, Pharmacokinetic Comparability Trial Between TAK-881 and HYQVIA in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy
A Study to Compare TAK-881 and HYQVIA in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Nishizawa Atsushi
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Contact for Clinical Trial Information
Takeda Pharmaceutical Company Limited
1-1, Doshomachi 4-chome, Chuo-ku, Osaka
+81-6-6204-2111
smb.Japanclinicalstudydisclosure@takeda.com
Recruiting
May. 06, 2025
May. 06, 2025
59
Interventional
single arm study
open(masking not used)
active control
single assignment
treatment purpose
1. Participant is willing and able to understand and fully comply with trial procedures and requirements, in the opinion of the investigator.
2. Participant has provided informed consent (that is, in writing, documented via a signed and dated informed consent Form [ICF]) and any required privacy authorization before the initiation of any trial procedures.
3. Participant has a documented diagnosis of CIDP or possible CIDP, as confirmed by a neurologist specializing/experienced in neuromuscular diseases and consistent with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2021 criteria.
4. Participant has responded to IgG treatment in the past (documented partial or complete resolution of neurological symptoms and deficits).
5. 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 grams per kilogram (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 less than or equal (<=) to 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 percentage (%) between the participant's pretrial IgG infusions are acceptable.
6. 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.
7. 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 the investigational medical product (IMP).
1. Participant with documented diagnosis of focal, multifocal, distal, or sensory CIDP, or possible focal, multifocal, distal, or sensory CIDP per the EFNS/PNS 2021 criteria.
2. 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.
3. 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 less than (<) 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.
4. 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.
5. Participant is required to take or has taken long-term systemic corticosteroids defined as dosages greater than (>) 20 milligrams per day (mg/day) prednisone-equivalent for >30 days within 3 months of screening.
Note: Participants using short-pulse dose corticosteroid course and oral daily corticosteroids <= 20mg/day prednisone-equivalent are allowed.
6. Participant has undergone plasma exchange within 3 months before screening.
7. Participant has immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with a high titer of antibody to myelin-associated glycoprotein.
8. Participant has immunoglobulin A (IgA) deficiency (IgA <0.07 grams per liter [g/L]) associated with known anti-IgA antibodies and a history of hypersensitivity to human immunoglobulin treatment.
9. Participant has a condition(s) which could alter protein catabolism and/or IgG use (for example [eg.] protein losing enteropathies, and nephrotic syndrome).
10. Participant has a history or clinical manifestations of chronic kidney disease, or glomerular filtration rate of <30 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) estimated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the time of screening.
11. 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.
12. 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 millimeters of mercury (mm Hg) and/or systolic blood pressure >160 mm Hg during the screening epoch confirmed on 2 measures >30 minutes apart).
13. Participant has an acquired or inherited thrombophilic disorder, such as protein C deficiency, protein S deficiency, antithrombin deficiency, and primary antiphospholipid antibody syndrome.
14. Participant has a history of deep vein thrombosis or arterial thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) within 12 months before screening.
15. 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.
16. Participant has a known history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, IGSC, and/or immune serum globulin infusions.
17. Participant has a known systemic hypersensitivity to any of the excipients of TAK-881/HYQVIA in accordance with the Investigator's Brochure (IB)/package insert/Summary of Product Characteristics (SmPC).
18. Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
19. 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 Human Immunodeficiency Virus (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.
20. Participant has clinically significant anemia that precludes repeated blood sampling during the trial, or hemoglobin level of <10.0 grams per deciliter (g/dL) at the time of screening.
21. 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 per microliter (cells/mcrL).
C) Absolute neutrophil count <1000 cells/mcrL.
22. If female, the participant is pregnant or lactating at the time of screening.
23. 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.
24. 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.
All Participants (HYQVIA and TAK-881)
Ramp-up Epoch:
Participants on IGIV or cIGSC will switch to HYQVIA during ramp-up epoch with gradually increasing doses/volumes. For participants switching from IGIV, first HYQVIA dose is given two weeks after their last IGIV infusion. For participants switching from cIGSC, first dose is given one week after a weekly infusion or two weeks after a bi-weekly infusion, using a SC investigational needle set.
Treatment Epoch:
After completing ramp-up, participants will enter HYQVIA dosing epoch 2-3 weeks later, depending on treatment interval. Those already on HYQVIA at screening will skip ramp-up and proceed directly to dosing phase, lasting 18 weeks for a 3-week interval and 20 weeks for 4-week interval. After HYQVIA PK sampling period, participants will switch to TAK-881 with a 1:1 dose conversion. TAK-881 dosing lasts 24 weeks with a SC infusion needle set.
Extension Epoch:
Post-TAK-881, participants will enter the extension epoch, continuing treatment for up to 3 years.
1. Baseline-Uncorrected Area Under the Curve During the Dosing Interval at Steady-State (AUC0-tau;ss) Based on Total Immunoglobulin G (IgG) Levels
Time Frame: 3-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 17, 21 days (post-infusion); 4-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 21, 28 days (post-infusion) of last infusion
1. Baseline-Uncorrected Area Under the Curve to the Last Measurable Concentration at Steady-State (AUClast,ss) Based on Total IgG Levels
Time Frame: 3-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 17, 21 days (post-infusion); 4-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 21, 28 days (post-infusion) of last infusion
2. Baseline-Uncorrected Time of the Last Measurable Concentration at Steady-State (Tlast,ss) Based on Total IgG Levels
Time Frame: 3-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 17, 21 days (post-infusion); 4-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 21, 28 days (post-infusion) of last infusion
3. Baseline-Uncorrected Maximum Observed Concentration at Steady-State (Cmax,ss) Based on Total IgG Levels
Time Frame: 3-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 17, 21 days (post-infusion); 4-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 21, 28 days (post-infusion) of last infusion
4. Baseline-Uncorrected Time to Maximum Concentration at Steady-State (Tmax,ss) Based on Total IgG Levels
Time Frame: 3-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 17, 21 days (post-infusion); 4-Week dosing: Day 1 (pre- and post-infusion), 24, 72, 120 hours and 7, 14, 21, 28 days (post-infusion) of last infusion
5. Total IgG Trough Level
Time Frame: Up to 4.06 years
6. Number of Participants With Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) who Experienced Relapse Related to Baseline
Time Frame: Baseline up to 24 weeks
Relapse is defined as an increase in the adjusted INCAT disability score by greater than and equal to (>=) 1-point relative to the baseline score. The INCAT disability score is a clinician-reported measure of a participant's level of arm and leg impairment. The arm and leg components of the INCAT are scored between 0 and 5 points (where arm = 0 indicates 'no upper limb problems' and arm = 5 indicates 'inability to use either arm for any purposeful movement', and leg = 0 indicates 'walking not affected', and leg = 5 indicates 'restricted to wheelchair, unable to stand and walk a few steps with help') and are summed to produce the overall INCAT disability score ranging between 0 and 10 points. A score of 0 indicates no signs of disability) and 10 indicates the most severe disability.
7. Change From Baseline in Hand Grip Strength
Time Frame: Baseline up to 24 weeks
Grip strength assessments conducted by prescribing physicians using the Martin Vigorimeter or the Jamar Dynamometer (as available at the site and performed per routine clinical practice).
8. Change From Baseline in Medical Research Council (MRC) Sum Score
Time Frame: Baseline up to 24 weeks
The MRC sum score measures muscle strength from both the left and right sides of the body on a scale of 0 to 5. The total MRC sum score ranges from 0 (paralysis) to 60 (normal strength), where higher score indicates better strength.
9. Change From Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) Centile Score
Time Frame: Baseline up to 24 weeks
The I-RODS is a validated, participants self-reported, linearly weighted overall disability scale that was specifically designed to capture current activity and social participation limitations in participants with immune-mediated peripheral neuropathies including CIDP. The I-RODS comprises 24 items for which participants are asked to rate their functioning related to a variety of everyday tasks at the moment of completion. The participant assigns a score between 0 and 2 to each item as follows: 0 (impossible to perform), 1 (performed with difficulty), 2 (easily performed) with a lower score indicating more severe activity and social participation limitations.
10. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Up to 4.06 years
11. Number of Participants With Infusion Withdrawals, Interruptions, and Infusion Rate Reductions due to TAK-881-related TEAEs
Time Frame: Up to Week 55
12. Number of Participants With Positive Binding Antibodies (Titer Greater than and equal to [>=] 1:160) and With Positive Neutralizing Antibodies to rHuPH20
Time Frame: Up to 4.06 years
13. Number of Infusions per Month at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to 4.06 years
14. Number of Infusions Sites (Needle Sticks) per Month at Full Dose With Both TAK-881 and HYQVIA in all Participant
Time Frame: Up to 4.06 years
15. Number of Infusions Sites (Needle Sticks) per Infusion at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to Week 55
16. Duration of Infusions (Minutes) at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to 4.06 years
17. Monthly Infusion Time (Minutes/Month) at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to 4.06 years
18. Maximum Tolerated Infusion Rate per Site (milliliter [mL]/hour/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to Week 55
19. Infusion Volume per Site (mL/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
Time Frame: Up to Week 55
20. Time of Infusion Preparation Measured by Healthcare provider (HCP)
Time Frame: Up to 4.06 years
Takeda Pharmaceutical Company Limited
Chubu Rosai Hospital IRB
1-10-6, Komei, Minato-ku, Nagoya city, Aichi, Japan, Aichi
+81-52-652-5511
Approval
Mar. 25, 2025
Yes
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
