A First-in-human Study of KT501 Administered Subcutaneously to Patients With Rheumatoid Arthritis (RA).

Официальное название

A Phase 1a, Open-Label, First-in-Human Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KT501 by a Single Subcutaneous Administration in Participants With Rheumatoid Arthritis

Обзор

This is a Phase 1, open-label, first-in-human study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of KT501 administered subcutaneously to participants with Rheumatoid Arthritis (RA).

Подробное описание

This is a Phase 1, open-label, first-in-human dose escalation study to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic of KT501 by a single subcutaneous administration in participants with Rheumatoid Arthritis (RA).

Up to a total of 5 cohorts with up to approximately 24 participants in total with RA will be enrolled. All participants will receive a single dose of KT501 on Day 1 and followed up until Week 12. For any participants with B cells lower than baseline level or lower limit quantification, whichever is lower, additional B cell follow up is required up to Week 48 after the study treatment.

Вмешательства

• Препарат KT501
  KT501 is a monoclonal antibody that depletes B cells including plasma cells by targeting CD19, BCMA and CD3.

Первичные конечные точки

• Incidence of Adverse Events [Срок оценки: From Baseline Up to 12 weeks]
• Incidence of Cytokine-release Syndrome (CRS) [Срок оценки: From Baseline Up to 12 Weeks]
• Changes in Pulse Rate from Baseline [Срок оценки: From Baseline Up to 12 Weeks]
• Changes in Respiratory Rate from Baseline [Срок оценки: From Baseline to 12 Weeks]
• Changes in Blood Pressure from Baseline [Срок оценки: From Baseline Up to Week 12]
• Changes in Temperature from Baseline [Срок оценки: From Baseline to 12 Weeks]
• Changes in Hematology Clinical Laboratory Results from Baseline [Срок оценки: From Baseline Up to 12 Weeks]
• Changes in Chemistry Clinical Laboratory Results from Baseline [Срок оценки: From Baseline Up to 12 Weeks]
• Changes in Urinalysis Clinical Laboratory Results from Baseline [Срок оценки: From Baseline Up to 12 Weeks]
• Changes in Coagulation Clinical Laboratory Results from Baseline [Срок оценки: From Baseline Up to 12 Weeks]

Вторичные конечные точки (12)

• Serum Concentrations of KT501 [Срок оценки: Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.]
• Incidence of Treatment-induced Anti-Drug Antibodies (ADAs) [Срок оценки: Pre-dose and on Day 1; Day 8, 11, 15, 22, 29, 43, 57 and 85.]
• To Determine Cmax [Срок оценки: Day 1 - Day 85]
• To Determine Tmax, Derived from Serum Concentration of each Dose of KT501 [Срок оценки: Day 1 - Day 85]
• Area Under the Serum-concentration Time Curve (AUC) from Time Zero to the Last Timepoint with Measurable Analyte Concentration (AUC0-t) [Срок оценки: Day 1 - Day 85]
• AUC from Time Zero to Infinity (AUCinf) [Срок оценки: Day 1 - Day 85]
• To Determine Terminal Half-Life (T1/2) [Срок оценки: Day 1 - Day 85]
• Total Body Clearance (CL/F) [Срок оценки: Day 1 - Day 85]
• Volume of Distribution During the Terminal Phase (Vz/F) [Срок оценки: Day 1 - Day 85]
• Change in Levels of B Cell Count [Срок оценки: Pre-dose on Day 1; Day 2, 3, 4, 5, 8, 11, 15, 22, 29, 43, 57 and 85.]
• Duration of B Cell Depletion [Срок оценки: Day 1 - Day 85]
• Change in Levels of Acute Inflammatory Markers [Срок оценки: Pre-dose and 6 hours post-dose on Day 1; Day 2, 3, 4, 5, 8, 15, 22, 29,, 57 and 85.]

Критерии участия

Критерии включения

• 18 to 75 years old
• Diagnosis of adult-onset RA for at least 6 months
• Moderately to severely active RA
• Inadequate treatment response as defined in the protocol
• RF + or ACPA+
• Stable use of traditional DMARDs is permitted
• Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Критерии исключения

• Functional class IV as defined by the ACR Classification of Functional Status in RA
• Presence of any concomitant autoimmune disease other than RA
• Active infection, history of serious recurrent or chronic infection
• History of progressive multifocal leukoencephalopathy
• Have a diagnosis or history of malignant disease within 5 years or breast cancer diagnosed within the previous 10 years.
• History of or planned organ transplant and/or autologous or allogeneic hematopoietic stem cell transplantation
• Receipt of live vaccine within 4 weeks
• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after study
• Women who are pregnant or breastfeeding
• Significant or uncontrolled medical disease that would preclude participant participation

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

Австралия · 1 центр

• Kali Study Site — Bayswater

Идентификаторы

NCT: NCT07234773 · KT501-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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