Clinical trial NCT05084053: A Study of TAK-771 in Japanese Participants With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Multifocal Motor Neuropathy (MMN)
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Multifocal Motor Neuropathy (MMN)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion criteria

1. Be a Japanese person.
2. The participant is male or female \>=18 years old at the time of screening.
3. 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.
4. 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.
5. 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:

   1. Screening and Baseline INCAT disability score between 3 and 7 inclusive.
   2. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities)
   3. 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.
   4. 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.
6. 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.
7. The participant is willing and able to sign an Informed Consent Form (ICF).
8. The participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria CIDP patients

1. Participants with focal atypical CIDP or pure sensory atypical CIDP or multifocal acquired demyelinating sensory and motor neuropathy (MADASAM).
2. Participants with any neuropathy of other causes, including:

   1. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth \[CMT\] disease), and hereditary sensory and autonomic neuropathies (HSANs).
   2. 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.
   3. Multifocal motor neuropathy (MMN).
   4. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy. MMN patients
3. 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
4. Participant with immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.
5. Participant with presence of prominent sphincter disturbance.
6. Participant with any central demyelinating disorders such as multiple sclerosis.
7. 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.)
8. 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).
9. Participant with a history of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) within 12 months prior to screening.
10. Participant with condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome).
11. 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.
12. 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.
13. 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.
14. 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.)
15. Participant has a known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin such as bee or wasp venom.
16. Participant with immunoglobulin A (IgA) deficiency and antibodies against IgA and a history of hypersensitivity.
17. Participant with an abnormal laboratory values at screening meeting any one of the following criteria:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN).
    2. Platelet count \<100,000 cells/microL.
    3. Absolute neutrophil count (ANC) \<1000 cells/microL.
18. 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.
19. Participant has received or is currently receiving treatment with immunomodulatory/immunosuppressive agents within 6 months prior to screening.
20. Participant has received or is currently receiving treatment with any corticosteroids dose within 8 weeks prior to screening, regardless of indication.
21. Participant has undergone PE within 3 months prior to screening.
22. 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.
23. Participant is nursing or intends to begin nursing during the course of the study.
24. 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.
25. Participant is a family member or employee of the investigator.
26. 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.

Primary outcomes:
measure: Epoch 1: Percentage of Participants With CIDP Who Experienced Relapse
timeFrame: Epoch 1: Baseline up to 6 months
measure: Epoch 1: Change From Baseline in Maximum Grip Strength in the More Affected Hand in Participants With MMN
timeFrame: Epoch 1: Baseline up to 6 months
Secondary outcomes:
measure: Epoch 1 and 2 (6 Months): Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Related SAEs and TEAEs
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Serious and Non-serious Adverse Reactions (ARs) Plus Suspected ARs
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With SAEs and/or TEAEs Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Related SAEs and TEAEs Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With TEAEs Temporally Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Serious and Non-serious ARs Plus Suspected ARs Temporally Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Systemic TEAEs Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Treatment-emergent Local Infusion Site Reactions Associated With Infusions
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 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
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1 and 2 (6 Months): Number of Participants With Positive Binding Antibodies, and Positive Neutralizing Antibodies to rHuPH20
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1: Percentage of Participants With Clinical Worsening of CIDP
timeFrame: Epoch 1: Baseline until end of Epoch 1 or relapse (up to 6 months)
measure: Epoch 1 and 2 (6 Months): Time to Relapse in Participants With CIDP
timeFrame: Epoch 1: Baseline up to 6 months; Epoch 2: Up to 6 months post-Epoch 1
measure: Epoch 1: Change From Pre-subcutaneous Treatment (Baseline) in R-ODS Total Score in Participants With CIDP
timeFrame: Epoch 1: Baseline up to 6 months
measure: Epoch 1: Change From Pre-subcutaneous Treatment (Baseline) in an Average of Handgrip Strength of Both Hands in Participants With CIDP and MMN
timeFrame: Epoch 1: Baseline up to 6 months
measure: Epoch 1: Change From Pre-subcutaneous Treatment (Baseline) Total Medical Research Council (MRC) Sum Score in Participants With MMN
timeFrame: Epoch 1: Baseline up to 6 months
measure: Epoch 1: Number of MMN Participants With Increased Guy's Neurological Disability Scale (GNDS) Score in Upper Limb and Lower Limb Categories
timeFrame: Epoch 1: Baseline up to 6 months
Other outcomes:
Locations:
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Chubu Rosai Hospital
state: Aichi
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Asahikawa
country: Japan
facility: Asahikawa Medical Center
state: Hokkaido
city: Amagasaki
country: Japan
facility: Kansai Rosai Hospital
state: Hyogo
city: Nishinomiya
country: Japan
facility: Hyogo College of Medicine Hospital
state: Hyogo
city: Kawasaki
country: Japan
facility: St.Marianna University School of Medicine Hospital
state: Kanagawa
city: Sendai
country: Japan
facility: Tohoku Medical and Pharmaceutical University Hospital
state: Miyagi
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Higashimatsuyama
country: Japan
facility: Higashimatsuyama Municipal Hospital
state: Saitama
city: Otsu
country: Japan
facility: Shiga University of Medical Science Hospital
state: Shiga
city: Yoshinogawa
country: Japan
facility: Tokushima National Hospital
state: Tokushima
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: