A Study to Evaluate the Pharmacokinetics and Safety of XEMBIFY Versus Gamunex-C in Participants With Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Официальное название

An Open-Label, Multicenter Study to Evaluate the Pharmacokinetics and Safety of XEMBIFY Versus Gamunex-C in Participants With Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Обзор

The main goal of the study is to find out whether XEMBIFY, given once a week under the skin, provides similar levels of immunoglobulin G in the blood over time as Gamunex-C, which is given into a vein once every 3 weeks in people with CIDP. Participants with CIDP will first have up to 28 days of screening to make sure they can join the study. Those who qualify will then start a 19-week treatment period with Gamunex-C. During this period, they will receive Gamunex-C through a vein once every 3 weeks, for a total of 7 doses. Approximately, one week after their last Gamunex-C dose, they will begin a 16-week treatment period with XEMBIFY under the skin, once a week for a total of 16 doses. Blood samples will be collected during both treatment periods to measure IgG level in the blood.

Вмешательства

• Биопрепарат Gamunex-C
  Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (IGIV-C 10%)
• Биопрепарат Xembify
  Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%)

Первичные конечные точки

• AUC in the IV Phase: Steady-state area under the concentration-time curve (AUC) of total IgG over a 3-week intravenous dosing interval (τ) (i.e., AUC(0-21days) in participants with CIDP [Срок оценки: Week 1 to 19 of IV Phase]
• AUC in the SC Phase: Steady-state AUC of total IgG over a weekly SC dosing interval (τ) (i.e., AUC(0-7days)) in participants with CIDP [Срок оценки: Week 1 to 16 of SC Phase]

Вторичные конечные точки (1)

• Steady-state mean trough (pre-dose) concentration of total IgG following IV administration of Gamunex-C 10% every 3 weeks SC administration of Xembify 20% once weekly [Срок оценки: Day 1 through End of Study Visit (approximately 35 weeks)]

Критерии участия

Критерии включения

• Have typical CIDP or a CIDP variant according to the 2021 criteria established by the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS). The level of diagnostic certainty may be CIDP or possible CIDP.
• Participants ≤ 90 kg in body weight and requiring an IGIV dose equivalent to 0.3-1.0 g/kg every three weeks (Q3W) inclusive and between 20-90 g of IGIV Q3W inclusive.
• Clinically stable on IGIV, defined as no recent change in CIDP treatment or experienced a CIDP relapse requiring treatment, within 12 weeks prior to Screening and through baseline visit.

Критерии исключения

• Diagnosis of polyneuropathy of any other cause (including multifocal motor neuropathy; monoclonal gammopathy of uncertain significance with anti-myelin-associated glycoprotein IgM antibodies; hereditary demyelinating neuropathy; polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome; lumbosacral radiculoplexus neuropathy; polyneuropathy associated with diabetes mellitus; polyneuropathy associated with systemic illnesses; or drug or toxin induced polyneuropathy).
• Severe diseases and conditions that are likely to interfere with evaluation of the study product or satisfactory conduct of the study such as the following:

• current malignancy or history of allogeneic bone marrow/stem cell transplant,
• cardiac insufficiency (New York Heart Association classes III/IV), cardiomyopathy, significant cardiac arrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension
• chronic kidney disease stage IV or V
• an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/µL \[1.0 × 10\^9/L\]), or human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome
• known bleeding disorders
• severe skin disease at the planned injection sites
• alcohol, drug or medication abuse, or
• other disorders where IGSC therapy would be contraindicated during the study.
• History of a thrombotic episode (including deep vein thrombosis, known hypercoagulable state, myocardial infarction, pulmonary embolism, or thromboembolic stroke)
• Known allergic or other severe adverse reactions to blood products including intolerability to previous IVIG up to 1 g/kg Q3W, history of hemolysis after IVIG infusion, aseptic meningitis, recurrent severe headache, hypersensitivity, or severe generalized skin reaction
• Has had a CIDP relapse requiring treatment modification within 12 weeks prior to Screening or between Screening and baseline visit
• Treatment with any of the following:

• alemtuzumab or rituximab within 12 months of Screening.
• cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, or fragment crystallizable receptor (FCRn) blockers, within six months of Screening
• plasma exchange or complement inhibitors within three months of Screening.
• changes to the following treatment within three months of Screening: methotrexate, azathioprine, or mycophenolate or any other immunosuppressants within six months of Screening
• participants on corticosteroids ≥ 20 mg/day prednisone equivalent. Participants on low dose corticosteroids (< 20 mg/day prednisone equivalent) may be enrolled if dose has been stable over the last three months prior to Screening and the dosage is not likely to be adjusted during the duration of the trial (inhaled or topical corticosteroids are allowed).
• Participants requiring an IGIV dose equivalent to:

• greater than 1.0 g/kg every three weeks (Q3W) or
• less than 0.3 g/kg Q3W or
• greater than 90 g of IGIV Q3W or
• less than 20 g of IGIV Q3W.
• Known IgA deficient patients with known antibodies against IgA
• Known significant proteinuria (≥ 3+ or known urinary protein loss >1 g/24 hours or nephrotic syndrome), acute renal failure, are on dialysis, and/or have severe renal impairment on Screening laboratory testing (blood urea nitrogen \[BUN\] > 3 times the upper limit of normal \[ULN\] or creatinine more than 1.5 times ULN).
• Screening values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding ≥ 2.5 times the ULN for the expected normal range for the testing laboratory.
• Hemoglobin levels < 10 g/dL at Screening.
• Current administration of anti-coagulation therapy which would make IGSC administration inadvisable per investigator judgement (i.e., vitamin K antagonists, nonvitamin K antagonist oral anticoagulants \[e.g., dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa\], and parenteral anticoagulants \[e.g., fondaparinux\]).
• Known hyperviscosity syndrome.
• Known HIV, chronic hepatitis B virus (HBV), or chronic hepatitis C virus (HCV) infection.
• Participation in another clinical trial within 30 days or if known, 5 half-lives of the interventional product prior to Screening (observational studies without investigative treatments \[non-interventional\] are permitted).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• GC2402 Study Site 104 — Rancho Mirage
• GC2402 Study Site 109 — Coral Springs
• GC2402 Study Site 105 — Miami
• GC2402 Study Site 103 — Port Charlotte
• GC2402 Study Site 110 — New York
• GC2402 Study Site 111 — Cordova
• GC2402 Study Site 106 — Sherman

Идентификаторы

NCT: NCT07540221 · GC2402

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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