NCT06680037招募中1 期
A Phase 1, Open-label Study to Evaluate the Safety and Clinical Activity of Azercabtagene Zapreleucel in Participants With B-cell Mediated Autoimmune Disorders
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 9
- 主要终点
- Number of Participants with Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The main objective of the study is to determine the recommended phase 2 dose (RP2D) of Azercabtagene zapreleucel (azer-cel).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PMS and RMS inclusion criteria:
- •Age 18 years to ≤60 years (inclusive) at screening.
- •Expanded Disability Status Scale (EDSS) score 3.0 - 6.5 (inclusive) at screening.
- •Diagnosis of primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (non-active or active), or Relapsing MS (RMS).
- •Documented evidence of disability progression independent of relapse (PIRA) at any point over the 12 months prior to the screening visit.
- •Willingness and ability to undergo lumbar puncture (LP) for cerebrospinal fluid (CSF) collection at protocol-specified timepoints, with no contraindications to the procedure in the opinion of the Investigator.
- •NMOSD inclusion criteria:
- •Between age 18 and ≤ 75 years, inclusive at the time of signing the informed consent.
- •EDSS score between 2.0 and 7.0 at screening, inclusive (for higher EDSS, the Investigator must assess that the participant is reasonably able to participate in the study).
- •Diagnosis of anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive at screening (verified by the allocated central laboratory) and Neuromyelitis Optica Spectrum Disorder (NMOSD).
- •Must meet the appropriate NMOSD treatment washout criteria prior to receiving lymphodepletion.
- •MG Inclusion criteria:
- •Age ≥18 and ≤75 years of age at the time of signing the informed consent.
- •Diagnosed with gMG at least 1 year prior to the date of signing the informed consent.
- •Confirmation of MG Diagnosis:
- •Positive serologic test for anti-acetylcholine receptor (AChR) antibodies or anti-muscle-specific kinase (MuSK) antibodies confirmed at screening AND
- •One of the following (either historical or during screening):
- •Abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation.
- •Positive anticholinesterase test (e.g., edrophonium chloride test).
- •Demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician.
- •MG activities of daily living (MG-ADL) score ≥6 at screening.
- •CIDP Inclusion criteria
- •Age ≥18 and ≤75 years of age at the time of signing the informed consent.
- •Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP, multifocal CIDP (also known as Lewis Sumner Syndrome). Separately, Autoimmune Nodopathy (AN) participants with anti-CNTN1 or anti-NF155/anti-NF186, as confirmed by serological testing, may be included.
- •CIDP Disease Activity Status (CDAS): CDAS score ≥3 at screening.
- •INCAT Disability Score: INCAT disability score ≥4 to ≤9 score at screening.
排除标准
- •History of malignancy that has not been in remission for at least 2 years.
- •Active venous thromboembolism (e.g., deep vein thrombosis or pulmonary embolism), clinically significant coagulopathy (e.g., disseminated intravascular coagulation), or current therapeutic anticoagulation (e.g., warfarin).
- •Viral and Tuberculosis (TB) Screening
- •Evidence of chronic active or history of hepatitis B virus (HBV).
- •Seropositive for human immunodeficiency virus (HIV) antibody.
- •History of bone marrow/hematopoietic stem cell or solid organ transplantation.
- •Prior treatment with any gene therapy product directed at any target (e.g. CAR T-cell therapy), with the exception of azer-cel.
- •Note: Other protocol-specified Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Azer-cel
Experimental
Participants will receive a single dose of intravenous (IV) infusion of azer-cel at different dose levels, on Day 0 of the treatment period.
干预措施: Azercabtagene zapreleucel (azer-cel) (Drug)
结局指标
主要结局
Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: From Day 0 to Day 28
DLT will be determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
次要结局
- Number of Participants with Treatment Emergent Adverse Events (TEAEs), Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)(Up to Day 720)
- Change From Baseline in CAR T-cell Toxicities(Baseline, up to Day 720)
- Pharmacokinetics (PK) Plasma Concentrations of Azer-cel(Up to Day 720)
- Pharmacodynamics (PD) Plasma Concentrations of Azer-cel(Up to Day 720)
- Time to Confirmed Disability Progression (CDP)(Up to Day 720)
- Time to Confirmed Disability Improvement (CDI)(Up to Day 720)
- Change From Baseline in Brain MRI Gadolinium Enhancing T1, New or Enlarging Hyperintense T2(Baseline, up to Day 720)
- Change From Baseline in Whole Brain Atrophy(Baseline, up to Day 720)
- Change from Baseline in Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) Total Score(Baseline, up to Day 720)
- Time to Relapse, as Defined by a 1 Point Change in Adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT)(Baseline, up to Day 720)
- Change From Baseline in Inflammatory Neuropathy Cause and Treatment (INCAT) Score(Baseline, up to Day 720)
- Change From Baseline in Modified Rankin Scale (mRS)(Baseline, up to Day 720)
- Change From Baseline in Visual Acuity on Landolt C Broken Ring Chart (Low Contrast Visual Acuity [LCVA]) and High Contrast Visual Acuity (HCVA)(Baseline, up to Day 720)
- Change from Baseline in the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r)(Baseline, up to Day 720)
研究者
研究点 (9)
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