Clinical trial NCT06747351: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
Keywords: Immunoglobulin
facilitated subcutaneous , Immunoglobulin;
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2024-12-24
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 24 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.

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. 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:

  1. Screening INCAT disability score of between 3 and 7 inclusive.
  2. Screening INCAT disability score of 2 (both points are from lower extremities).
  3. 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.
  4. 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 t 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:

  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, amyloidosis.
  3. Multifocal motor neuropathy (MMN).
  4. 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 (for example \[eg.\] 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 less than or equal to (\<=) 10 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 IV immunoglobulin, SC immunoglobulin, 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:

  1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \>2.5\*upper limit of normal (ULN).
  2. Platelet count \<100,000 cells per microliter (cells/µL).
  3. 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 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.

Primary outcomes:
measure: Baseline-Uncorrected Area Under the Curve During the Dosing Interval at Steady-State (AUC0-tau;ss) Based on Total Immunoglobulin G (IgG) Levels
timeFrame: 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 outcomes:
measure: Baseline-Uncorrected Area Under the Curve to the Last Measurable Concentration at Steady-State (AUClast,ss) Based on Total IgG Levels
timeFrame: 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
measure: Baseline-Uncorrected Time of the Last Measurable Concentration at Steady-State (Tlast,ss) Based on Total IgG Levels
timeFrame: 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
measure: Baseline-Uncorrected Maximum Observed Concentration at Steady-State (Cmax,ss) Based on Total IgG Levels
timeFrame: 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
measure: Baseline-Uncorrected Time to Maximum Concentration at Steady-State (Tmax,ss) Based on Total IgG Levels
timeFrame: 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
measure: Total IgG Trough Level
timeFrame: Up to 4.06 years
measure: Number of Participants With Adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) who Experienced Relapse Related to Baseline
timeFrame: Baseline up to 24 weeks
measure: Change From Baseline in Hand Grip Strength
timeFrame: Baseline up to 24 weeks
measure: Change From Baseline in Medical Research Council (MRC) Sum Score
timeFrame: Baseline up to 24 weeks
measure: Change From Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) Centile Score
timeFrame: Baseline up to 24 weeks
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 4.06 years
measure: Number of Participants With Infusion Withdrawals, Interruptions, and Infusion Rate Reductions due to TAK-881-related TEAEs
timeFrame: Up to Week 55
measure: Number of Participants With Positive Binding Antibodies (Titer Greater than and equal to [>=] 1:160) and With Positive Neutralizing Antibodies to rHuPH20
timeFrame: Up to 4.06 years
measure: Number of Infusions per Month at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to 4.06 years
measure: Number of Infusions Sites (Needle Sticks) per Month at Full Dose With Both TAK-881 and HYQVIA in all Participant
timeFrame: Up to 4.06 years
measure: Number of Infusions Sites (Needle Sticks) per Infusion at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to Week 55
measure: Duration of Infusions (Minutes) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to 4.06 years
measure: Monthly Infusion Time (Minutes/Month) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to 4.06 years
measure: Maximum Tolerated Infusion Rate per Site (milliliter [mL]/hour/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to Week 55
measure: Infusion Volume per Site (mL/site) at Full Dose With Both TAK-881 and HYQVIA in all Participants
timeFrame: Up to Week 55
measure: Time of Infusion Preparation Measured by Healthcare provider (HCP)
timeFrame: Up to 4.06 years
Other outcomes:
Locations:
city: Rockledge
country: United States
facility: Knight Neurology
state: Florida
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: