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RecruitingInterventionalPhase 1

A Phase 1, Open-label Study to Evaluate the Safety and Clinical Activity of Azercabtagene Zapreleucel in Participants With B-cell Mediated Autoimmune Disorders

NCT ID: NCT06680037Sponsor: TG Therapeutics, Inc.Last updated: 2026-06-18

Summary

The main objective of the study is to determine the recommended phase 2 dose (RP2D) of Azercabtagene zapreleucel (azer-cel).

Arms & interventions

  • DrugAzercabtagene zapreleucel (azer-cel)

    IV infusion

Outcome measures

Primary

  • Number of Participants with Dose-Limiting Toxicities (DLTs)

    DLT will be determined using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Time frame: From Day 0 to Day 28

Secondary

  • Number of Participants with Treatment Emergent Adverse Events (TEAEs), Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs)

    Time frame: Up to Day 720

  • Change From Baseline in CAR T-cell Toxicities

    Time frame: Baseline, up to Day 720

  • Pharmacokinetics (PK) Plasma Concentrations of Azer-cel

    Time frame: Up to Day 720

  • Pharmacodynamics (PD) Plasma Concentrations of Azer-cel

    Time frame: Up to Day 720

  • Time to Confirmed Disability Progression (CDP)

    Time frame: Up to Day 720

  • Time to Confirmed Disability Improvement (CDI)

    Time frame: Up to Day 720

  • Change From Baseline in Brain MRI Gadolinium Enhancing T1, New or Enlarging Hyperintense T2

    Time frame: Baseline, up to Day 720

  • Change From Baseline in Whole Brain Atrophy

    Time frame: Baseline, up to Day 720

  • Change From Baseline in Modified Rankin Scale (mRS)

    Time frame: 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)

    Time frame: Baseline, up to Day 720

  • Change from Baseline in Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) Total Score

    Time frame: Baseline, up to Day 720

  • Change from Baseline in the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r)

    Time frame: Baseline, up to Day 720

  • Time to Relapse, as Defined by a 1 Point Change in Adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT)

    Time frame: Baseline, up to Day 720

  • Change From Baseline in Inflammatory Neuropathy Cause and Treatment (INCAT) Score

    Time frame: Baseline, up to Day 720

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: PMS and RMS inclusion criteria: 1. Age 18 years to ≤60 years (inclusive) at screening. 2. Expanded Disability Status Scale (EDSS) score 3.0 - 6.5 (inclusive) at screening. 3. Diagnosis of primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (non-active or active), or Relapsing MS (RMS). 4. Documented evidence of disability progression independent of relapse (PIRA) at any point over the 12 months prior to the screening visit. NMOSD inclusion criteria: 1. Between age 18 and 65 years, inclusive at the time of signing the informed consent. 2. 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). 3. Diagnosis of anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive at screening (verified by the allocated central laboratory) and Neuromyelitis Optica Spectrum Disorder (NMOSD). 4. Must meet the appropriate NMOSD treatment washout criteria prior to receiving lymphodepletion. MG Inclusion criteria: 1. Age ≥18 and ≤70 years of age at the time of signing the informed consent. 2. Diagnosed with gMG at least 1 year prior to the date of signing the informed consent. 3. Confirmation of MG Diagnosis: 1. Positive serologic test for anti-acetylcholine receptor (AChR) antibodies or anti-muscle-specific kinase (MuSK) antibodies confirmed at screening AND 2. 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. 4. MG activities of daily living (MG-ADL) score ≥6 at screening. CIDP Inclusion criteria 1. Age ≥18 and ≤70 years of age at the time of signing the informed consent. 2. Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP, multifocal CIDP (also known as Lewis Sumner Syndrome). 3. CIDP Disease Activity Status (CDAS): CDAS score ≥3 at screening. 4. INCAT Disability Score: INCAT disability score ≥4 to ≤9 score at screening. General Exclusion Criteria: 1. History of malignancy that has not been in remission for at least 2 years. 2. Viral Screening 1. Evidence of chronic active or history of hepatitis B virus (HBV). 2. Seropositive for human immunodeficiency virus (HIV) antibody. 3. History of bone marrow/hematopoietic stem cell or solid organ transplantation. 4. Prior treatment with adoptive T-cell therapy or any gene therapy product directed at any target (e.g. CAR T-cell therapy). Note: Other protocol-specified Inclusion/Exclusion criteria may apply.

Study locations (8)

TG Therapeutics Investigational Trial Site

La Jolla, California, 92093

Recruiting

TG Therapeutics Investigational Trial Site

Ann Arbor, Michigan, 48019

Recruiting

TG Therapeutics Investigational Trial Site

Omaha, Nebraska, 68198

Recruiting

TG Therapeutics Investigational Trial Site

New York, New York, 10025

Recruiting

TG Therapeutics Investigational Trial Site

Rochester, New York, 14642

Recruiting

TG Therapeutics Investigational Trial Site

Cleveland, Ohio, 44195

Recruiting

TG Therapeutics Investigational Trial Site

Columbus, Ohio, 43210

Recruiting

TG Therapeutics Investigational Trial Site

Milwaukee, Wisconsin, 53226

Recruiting
A Study to Assess the Safety and Clinical Activity of Azer-cel in Participants With B-cell Mediated Autoimmune Disorders | Cancerify