A Study to Compare TAK-881 and HYQVIA in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Official title

A Phase 3, Single-Arm, Multiple-Dose, Pharmacokinetic Comparability Trial Between TAK-881 and HYQVIA in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Overview

The main aim of this study is to evaluate the pharmacokinetic (PK) comparability between TAK-881 and HYQVIA subcutaneous (SC) administration for maintenance therapy of CIDP. The participants who are already receiving intravenous immunoglobulin G (IGIV), conventional subcutaneous intravenous immunoglobulin G (cIGSC), or HYQVIA will be treated with the same dose equivalent as their prior IG treatment with HYQVIA for 20 weeks followed by TAK-881 for 24 weeks. Participants will need to visit the clinic every 3 or 4 weeks until they enter the extension phase. In the extension phase, home infusions are allowed, and visits will occur between every 12 weeks and 24 weeks.

Detailed description

The study includes a screening phase, a ramp-up phase (if needed), a HYQVIA treatment phase, a TAK-881 treatment phase, and an extension phase. Participants who have been receiving cIGSC or IGIV prior to the study will enter a HYQVIA ramp-up phase, starting 1 to 2 weeks after their last pre-study cIGSC or IGIV dose. Participants already on HYQVIA at the time of screening will proceed directly to the treatment phase. After the TAK-881 dosing phase, participants will move on to the TAK-881 extension phase, with the preference for subsequent infusions in the extension phase to be administered by the participant or caregiver at home.

Interventions

• Biological TAK-881
  Participants will receive SC infusion of TAK-881.
• Biological HYQVIA
  Participants will receive SC infusion of HYQVIA.
• Device SC Investigational Needle Sets
  The single-use only SC needle set will be used to administer TAK-881/HYQVIA to the target depth below the skin surface. One needle set (single or bifurcated) will be used per infusion.

Primary outcome measures

• 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]

Secondary outcome measures (12)

• 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]
• 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]
• 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]
• 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]
• Total IgG Trough Level [Time frame: Up to 4.06 years]
• Number of Participants With Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) who Experienced Relapse Related to Baseline [Time frame: Baseline up to 24 weeks]
• Change From Baseline in Hand Grip Strength [Time frame: Baseline up to 24 weeks]
• Change From Baseline in Medical Research Council (MRC) Sum Score [Time frame: Baseline up to 24 weeks]
• Change From Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) Centile Score [Time frame: Baseline up to 24 weeks]
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time frame: Up to 4.06 years]
• Number of Participants With Infusion Withdrawals, Interruptions, and Infusion Rate Reductions due to TAK-881-related TEAEs [Time frame: Up to Week 55]
• 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]

Eligibility criteria

Inclusion criteria

• Participant is willing and able to understand and fully comply with trial procedures and requirements, in the opinion of the investigator.
• 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.
• 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.
• Participant has responded to IgG treatment in the past (documented partial or complete resolution of neurological symptoms and deficits).
• 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.
• Participant has an INCAT disability score between 0 and 7 (inclusive). Participants will be eligible if one of the below eligibility criteria are met:

• Screening INCAT disability score of between 3 and 7 inclusive.
• Screening INCAT disability score of 2 (both points are from lower extremities).
• 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.
• 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 the investigational medical product (IMP).

Exclusion criteria

• 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.
• Participant has any neuropathy of other causes, including:

• Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN), Charcot-Marie-Tooth (CMT) disease, and hereditary sensory and autonomic neuropathies (HSANs).
• 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.
• Multifocal motor neuropathy (MMN).
• Drug, biologic, chemotherapy, or toxin-induced peripheral neuropathy.
• 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.

• 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 (e.g. efgartigimod), and chemotherapeutic drugs, within 6 months of screening.
• 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 <= 20 mg/day prednisone-equivalent are allowed.

• Participant has undergone plasma exchange within 3 months before screening.
• Participant has immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with a high titer of antibody to myelin-associated glycoprotein.
• 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.
• Participant has a condition(s) which could alter protein catabolism and/or IgG use (for example \[eg.\] protein losing enteropathies, and nephrotic syndrome).
• 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.
• 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.

• 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).
• Participant has an acquired or inherited thrombophilic disorder, such as protein C deficiency, protein S deficiency, antithrombin deficiency, and primary antiphospholipid antibody syndrome.
• Participant has a history of deep vein thrombosis or arterial thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) within 12 months before screening.
• 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, IGSC, and/or immune serum globulin infusions.
• 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).
• Participant has a known systemic hypersensitivity to hyaluronidase or rHuPH20.
• 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.

• 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.
• Participant has any of the following laboratory values at screening:

• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5\*upper limit of normal (ULN).
• Platelet count <100,000 cells per microliter (cells/µL).
• Absolute neutrophil count <1000 cells/µL.
• If female, the participant is pregnant or lactating at the time of screening.
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 16 centers

• HonorHealth Neurology — Scottsdale
• Stanford Neuroscience Health Center — Palo Alto
• Yale University School of Medicine — New Haven
• Neurology Associates — Maitland
• Knight Neurology — Rockledge
• The Washington University — St Louis
• NYU Langone Health — New York
• University of North Carolina (UNC) — Chapel Hill
• … and 8 more centers

Italy · 9 centers

• Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale San Raffaele — Milan
• IRCCS Istituto Clinico Humanitas — Rozzano
• Azienda Ospedaliero - Universitaria San Luigi Gonzaga — Orbassano
• ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia — Brescia
• Ospedale San Martino — Genova
• Az Ospedaliera Universitaria Policlinico G Martino — Messina
• Fondazione Istituto Neurologico Casimiro Mondino — Pavia
• Azienda Ospedaliero Universitaria Pisana — Pisa
• … and 1 more center

Japan · 8 centers

• Japan Organization of Occupational Health and Safety Chubu Rosai Hospital — Nagoya
• Kumamoto University Hospital — Kumamoto
• Tohoku Medical and Pharmaceutical University Hospital — Sendai
• Nara Medical University Hospital — Kashihara
• Higashimatsuyama Municipal Hospital — Higashi-Matsuyama
• Shiga University of Medical Science Hospital — Ōtsu
• Tokushima University Hospital — Tokushima
• Juntendo University Hospital — Bunkyo-ku

Germany · 5 centers

• Universitätsklinikum Mannheim GmbH — Mannheim
• University of Ulm — Ulm
• Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg — Marburg
• Medizinische Hochschule Hannover — Hanover
• Charite - Universitatsmedizin Berlin — Berlin

Poland · 4 centers

• Oddzial Kliniczny Neurologii — Krakow
• Clinirem Sp zo.o. — Lublin
• Warszawski Uniwersytet Medyczny — Warsaw
• Copernicus Podmiot Leczniczy — Gdansk

Argentina · 2 centers

• INECO — Rosario
• Instituto Argentino de Investigacion Neurologica (IADIN) — Buenos Aires

Denmark · 2 centers

• Copenhagen University Hospital — Copenhagen
• Aarhus Universitetshospital — Aarhus

Greece · 2 centers

• Attikon University General Hospital — Athens
• University General Hospital of Patras — Patras

Spain · 2 centers

• Hospital de La Santa Creu I San Pau — Barcelona
• Hospital Universitari i Politecnic La Fe — Valencia

Czechia · 1 center

• Fakultni nemocnice Hradec Kralove — Hradec Králové

Sweden · 1 center

• Sahlgrenska Universitetssjukhuset — Gothenburg

Identifiers

NCT: NCT06747351 · TAK-881-3003 · 2024-517450-95-00 · jRCT2041250014

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗