An Open-label Study of AZD0120 in Adults With Multiple Sclerosis

Официальное название

A Phase 1b, Open-label, Multi-center, Randomized Study Evaluating the Safety and Tolerability of AZD0120, an Autologous CD19/BCMA Targeting Chimeric Antigen Receptor T-cells, in Adults With Refractory Relapsing or Progressive Multiple Sclerosis

Обзор

This trial is a Phase 1b, open-label, multi-center, clinical study of AZD0120, a BCMA/CD19 dual targeting CAR+ T-cell therapy, to evaluate the safety and tolerability in adult participants with Multiple Sclerosis.

Подробное описание

This study will evaluate AZD0120 for safety, including DLTs and TEAEs, by the SRC for determination of the Recommended Phase 2 dose for each disease cohort. Approximately 9-12 participants will be evaluated per disease cohort.

Вмешательства

• Биопрепарат AZD0120 - Regimen 1
  Regimen 1, infusion of AZD0120
• Биопрепарат AZD0120 - Regimen 2
  Regimen 2, infusion of AZD0120

Первичные конечные точки

• Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS) [Срок оценки: Day 1 to day 29, and over 104 weeks]
• Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS) [Срок оценки: Day 1 to day 29, and over 104 weeks]
• Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS) [Срок оценки: Day 1 to day 29, and over 104 weeks]
• Evaluate the safety, and tolerability of AZD0120 in participants with MS (disease cohort 1: RMS; disease cohort 2: PMS) [Срок оценки: Day 1 to day 29, and over 104 weeks]

Вторичные конечные точки (12)

• Evaluate the optimum regimen with AZD0120 in MS participants to determine the RP2D in each disease cohort [Срок оценки: Over 104 weeks]
• Evaluate the optimum regimen with AZD0120 in MS participants to determine the RP2D in each disease cohort [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]
• Evaluate the preliminary efficacy of AZD0120 in RMS and PMS [Срок оценки: Over 104 weeks]

Критерии участия

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

• Age ≥ 18-years-old to ≤ 60-years-old at the time of consent

Type of Participant and Disease Characteristics

• Written informed consent in accordance with federal, local, and institutional guidelines
• Adequate physiological function and reserve at screening

RMS Cohort Specific Inclusion Criteria

• Diagnosis of RMS according to the 2024 McDonald Criteria (Montalban et al 2025) or diagnosis of relapsing, active SPMS according to Lublin et al 2014.
• Participants should have an EDSS of ≤ 6.5 at screening.
• Evidence of active disease (clinical relapses and MRI activities within 2 years prior to screening), or intolerance, while on a high efficacy disease-modifying therapy for ≥ 6 months.

PMS Cohort Specific Inclusion Criteria

• Diagnosis of PPMS according to the 2024 McDonald Criteria (Montalban et al 2025) or non-relapsing SPMS according to Lublin et al 2014.
• Participants must have an EDSS of ≥ 3.0 and ≤ 6.5 at screening.
• Inadequate response ≥ 1 heDMT with ≥ 6 months treatment or intolerance.

Критерии исключения

Participants are excluded from the study if any of the following criteria apply:

• Any prior CAR-T or CAR-NK cell exposure.
• Underwent splenectomy within 12 months prior to signing the ICF.
• Received a solid organ transplant at any time or on an active transplant waiting list.
• Prior treatment with autologous hematopoietic stem cell transplantation or total lymphoid irradiation.
• Cardiac conditions or any other significant cardiac condition that would present undue risk to the participant in the investigator's opinion:
• Any other central nervous system disease including epilepsy, convulsive seizures, organic encephalopathy syndrome, non-MS related paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease or associated movement disorder, psychosis, CNS vasculitis, or any other neurological disease that may impact the ability to evaluate neurotoxicity. History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics.
• Participant has significant psychiatric condition (active or history of).
• History of other immune-mediated disease that required continued systemic immunosuppression/systemic disease-modifying agents.
• Evidence of clinically significant bleeding or active bleeding diathesis within 90 days before screening
• History of malignancy or ongoing treatment for prior malignancy.
• Inborn error of immunity and/or primary immunodeficiency.
• Seropositive for HIV or HTLV (including any history of HIV or HTLV).
• Active viral (any etiology, HBV, HCV) hepatitis are excluded.
• Major surgery within 4 weeks prior to apheresis or lymphodepletion or has surgery planned during the study or within 4 weeks after study treatment administration.
• Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment, whichever is longer.
• Unwilling or unsafe to proceed with CSF exams based on coagulopathy or anatomy or other considerations in the judgment of the study investigator.
• Any contraindications to LP.
• Participants not willing, able, or are unsafe to take MRI scans as per protocol.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• Research Site — Tucson
• Research Site — Aurora
• Research Site — Washington D.C.
• Research Site — St Louis
• Research Site — New York
• Research Site — New York
• Research Site — Cleveland
• Research Site — Seattle
• … и ещё 1 центр

Австралия · 4 центра

• Research Site — Liverpool
• Research Site — Melbourne
• Research Site — Melbourne
• Research Site — Waratah

Германия · 3 центра

• Research Site — Leipzig
• Research Site — Magdeburg
• Research Site — Würzburg

Великобритания · 2 центра

• Research Site — Cambridge
• Research Site — London

Канада · 1 центр

• Research Site — Montreal

Идентификаторы

NCT: NCT07224373 · D831DC00001 · 29707

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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