A Study of TAK-771 in Japanese Participants With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Multifocal Motor Neuropathy (MMN)

Study Overview
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Brief Summary
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The main aim of the study is to check for side effects from TAK-771, and to check how well TAK-771 controls symptoms in Japanese participants with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) The participants will be treated with TAK-771 for 45 months as a maximum. There will be many clinic visits. The number of visits will depend on the infusion cycles of study drug (every 2, 3, or 4 weeks).

Official Title
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A Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of TAK-771 for the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Multifocal Motor Neuropathy (MMN) in Japanese Subjects

Conditions
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Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), Multifocal Motor Neuropathy (MMN)

Intervention / Treatment
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* Drug: TAK-771


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Be a Japanese person. The participant is male or female >=18 years old at the time of screening. Participant has a documented diagnosis of definite or probable CIDP (focal atypical CIDP and pure sensory atypical CIDP will be excluded) or definite or probable MMN, as confirmed by a neurologist specializing/experienced in neuromuscular diseases to be consistent with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 criteria. Participant has responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IVIG treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 g/kg BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of intravenous immunoglobulin (IVIG) treatment must be between 2 and 6 weeks (inclusive). Variations in the dosing interval of up to ±7 days or monthly dose amount of up to +or-20% between participant's pre-study IgG infusions are within acceptable limits. CIDP participants only - INCAT disability score between 0 and 7 (inclusive). Participants with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater documented in the medical record. Participants will be eligible if one of the below eligibility criteria are met: Screening and Baseline INCAT disability score between 3 and 7 inclusive. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities) Screening and/or Baseline 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 prior to screening. If a score was greater than 2 documented in the medical record prior to screening at least 2 points must be from lower extremities. Screening and/or Baseline 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 prior to screening, at least 2 points must be from lower extremities. If female of childbearing potential, the participant must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of IP. The participant is willing and able to sign an Informed Consent Form (ICF). The participant is willing and able to comply with the requirements of the protocol. Exclusion Criteria CIDP patients Participants with focal atypical CIDP or pure sensory atypical CIDP or multifocal acquired demyelinating sensory and motor neuropathy (MADASAM). Participants with 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, and amyloidosis. Multifocal motor neuropathy (MMN). Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy. MMN patients Participant with other neuropathies (eg, diabetic, lead, porphyric or vasculitic neuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, Lyme neuroborreliosis, post radiation neuropathy, hereditary neuropathy with liability to pressure palsies, CMT neuropathies, meningeal carcinomatosis). CIDP/MMN Patients Participant with immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein. Participant with presence of prominent sphincter disturbance. Participant with any central demyelinating disorders such as multiple sclerosis. Participant with any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of endpoint measures, including (but not limited to) arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy. (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 study, provided the electrodiagnostic criteria are consistent with the diagnosis of a definite or probable CIDP consistent with the EFNS/PNS 2010 criteria and the participant agrees to maintain adequate glycemic control.) Participant with congestive heart failure (New York Heart Association [NYHA] class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (defined as diastolic blood pressure >100 mmHg and/or systolic blood pressure >160 mmHg). Participant with a history of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening. Participant with condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome). Participant with a known history of chronic kidney disease, or glomerular filtration rate of <60 mL/min/1.73m^2 estimated based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at the time of screening. Participant with active malignancy requiring chemotherapy and/or radiotherapy, or history of malignancy with less than 2 years of complete remission prior to screening. Exceptions to this exclusion are: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment. Participant with clinically significant anemia that precludes repeated blood sampling during the study, or hemoglobin (Hgb) level of <10.0 g/dL at the time of screening. Participant with a known history of hypersensitivity or ARs such as urticaria, breathing difficulty, severe hypotension, or anaphylaxis following administration of human blood products such as human IgG, albumin, or other blood components. (Clinically non-significant skin reactions, as per the investigator's and the sponsor medical monitor's discretion, do not meet this exclusion criterion. Clinically non-significant skin reactions may include local reactions to injection such as injection site's itching, redness, erythema, or swelling.) Participant has a known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin such as bee or wasp venom. Participant with immunoglobulin A (IgA) deficiency and antibodies against IgA and a history of hypersensitivity. Participant with an abnormal laboratory values at screening meeting any one of the following criteria: Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN). Platelet count <100,000 cells/microL. Absolute neutrophil count (ANC) <1000 cells/microL. Participant has a known history of 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 1/2. Participant has received or is currently receiving treatment with immunomodulatory/immunosuppressive agents within 6 months prior to screening. Participant has received or is currently receiving treatment with any corticosteroids dose within 8 weeks prior to screening, regardless of indication. Participant has undergone PE within 3 months prior to screening. Participant has any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study. Participant is nursing or intends to begin nursing during the course of the study. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. Participant is a family member or employee of the investigator. Participants with known acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of developing thrombotic events. Examples include a. Hereditary thrombophilia: i. Factor V Leiden mutation. ii. Prothrombin 20210A mutation. iii. Protein C deficiency. iv. Protein S deficiency. v. Anti-thrombin deficiency. b. Acquired thrombophilia: i. Anti-phospholipid antibody syndrome. ii. Activated protein C Resistance acquired. iii. Homocystinemia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TAK-771 for CIDP Participants<br>TAK-771 includes Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20). Participants will receive subcutaneous infusion of rHuPH20 solution at a dose of 80 U/g IgG first, followed by SC infusion of 10% IGI within 10 minutes of completion of the infusion of rHuPH20 solution, every 2, 3, or 4 weeks. | Drug: TAK-771<br>* Intervention description; Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20)<br>* Other names: Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase;|
| Experimental: Cohort 2: TAK-771 for MMN Participants<br>TAK-771 includes IGI 10% and rHuPH20. Participants will receive subcutaneous infusion of rHuPH20 solution at a dose of 80 U/g IgG first, followed by SC infusion of 10% IGI within 10 minutes of completion of the infusion of rHuPH20 solution, every 2, 3, or 4 weeks. | Drug: TAK-771<br>* Intervention description; Immune Globulin Infusion (IGI) 10% and Recombinant Human Hyaluronidase (rHuPH20)<br>* Other names: Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with CIDP who Experienced Relapse in Epoch 1 | Relapse is defined as worsening of functional disability defined as an increase of >=1 point relative to the pre-subcutaneous (pre-SC) treatment baseline score in adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. The INCAT disability scale is the most widely used assessment tool to measure the functional activity level of patients with CIDP. The INCAT disability scale consists of upper and lower extremity components, with a maximum of 5 points for the upper extremities (arm disability) and a maximum of 5 points for the lower extremities (leg disability), which are summed for an overall INCAT disability score ranging from 0 to 10 points, where 0 is normal and 10 is severely incapacitated. An adjusted INCAT disability score is the same as the INCAT disability score, with the only exception in the exclusion of changes from 0 (normal) to 1 (minor symptoms) (or vice versa) in upper limb function. | 6 Months | 
| Change in Maximum Grip Strength in the More Affected Hand in Epoch 1 for Participants with MMN | Change in maximum grip strength in the more affected hand in Epoch 1 for participants with MMN will be reported. Per baseline measurement point, investigators will judge which of both hands is more affected. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) |  | 45 Months | 
| Number of Participants with Serious Adverse Events (SAEs) |  | 45 Months | 
| Number of Participants with Serious and Nonserious Adverse Reactions (ARs) plus Suspected ARs |  | 45 Months | 
| Number of Participants with SAEs Associated with Infusions |  | 45 Months | 
| Number of Participants with TEAEs Associated with Infusions |  | 45 Months | 
| Number of Participants with AEs Temporally Associated with Infusions | AEs temporally associated with infusions defined as AEs occurring during or within 72 hours after completion of an infusion. | 45 Months | 
| Number of Participants with Serious and Nonserious ARs plus Suspected ARs Associated with Infusions |  | 45 Months | 
| Number of Participants with Treatment-emergent Systemic AEs Associated with Infusions |  | 45 Months | 
| Number of Participants with Treatment-emergent Local Infusion Site Reactions Associated with Infusions |  | 45 Months | 
| Number of Infusions for which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped due to Intolerability and/or AEs |  | 45 Months | 
| Number of Participants who Have Positive Titer (>=160) Binding Antibodies, or Neutralizing Antibodies, to rHuPH20 |  | 45 Months | 
| Percentage of Participants with CIDP who Experienced Worsening in Epoch 1 | Worsening defined as a >=8 kilo Pascal (kPa) decrease in the hand grip strength in the more affected hand) OR >=4 points decrease in Rasch Built Overall Disability Scale (R-ODS) relative to the pre-SC treatment baseline score at 2 consecutive time points. The R-ODS is a patient self-reported, linearly-weighted overall disability scale that was specifically designed to capture activity and social participation limitations in patients with immune-mediated peripheral neuropathies including CIDP. The R-ODS is comprised of 24 items for which participants are asked to rate their functioning (ie, no difficulty, some difficulty, or could not do) related to a variety of everyday tasks at the moment of completion. | 6 Months | 
| Time to Relapse in Participants with CIDP | Time to relapse is defined as time from the date of the first SC administration of TAK-771 to the date of relapse. | 45 Months | 
| Change from Baseline in R-ODS Score in Epoch 1 for Participants with CIDP | The R-ODS is a patient self-reported, linearly-weighted overall disability scale that was specifically designed to capture activity and social participation limitations in patients with immune-mediated peripheral neuropathies including CIDP. The R-ODS is comprised of 24 items for which participants are asked to rate their functioning (ie, no difficulty, some difficulty, or could not do) related to a variety of everyday tasks at the moment of completion. | 6 Months | 
| Change from Baseline in an Average of Handgrip Strength of Both Hands in Epoch 1 for Participants with CIDP |  | 6 Months | 
| Medical Research Council (MRC) Sum Score in Epoch 1 for Participants with MMN | The MRC sum score will serve as a measure of muscle strength. The following muscles on each side of the body are examined and the strength of each muscle is rated according to the MRC scale: deltoids, biceps, wrist extensors, iliopsoas, quadriceps, and anterior tibialis. The MRC scale ranges from 0 to 5, where: 0 = no visible contraction; 1 = visible contraction without movement of the limb; 2 = movement of the limb but not against gravity; 3 = movement against gravity over (almost) the full range; 4 = movement against gravity and resistance; and, 5 = normal. All scores from both left and right side of the body are summed to obtain the MRC sum score. The MRC sum score ranges from 0 (paralysis) to 60 (normal strength). | 6 Months | 
| Guy's Neurological Disability Scale (GNDS) in Upper Limb and Lower Limb Categories in Epoch 1 for Participants with MMN | Guy's Neurological Disability Scale is a questionnaire which consists of 12 separate categories (4 to 8 questions per category). The categories include: cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and others. In the current study, only 2 categories; upper limb function and the lower limb function will be used for assessment of the disability of participants with MMN. The severity of each subscale is graded from 0 (normal function) to 5 (total loss of function) based according to severity and impact on the individual. | 6 Months | 
| Change from Baseline in an Average of Handgrip Strength of Both Hands in Epoch 1 for Participants with MMN |  | 6 Months |