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

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

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

Study Overview

• Status: Recruiting
• Conditions: B-cell Mediated Autoimmune Disorders
• Intervention / Treatment: Drug: Azercabtagene zapreleucel (azer-cel)

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: TG Therapeutics Clinical Support Team; Phone Number: 1-877-575-8489; Email: clinicalsupport@tgtxinc.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • TG Therapeutics Investigational Trial Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48019
      • Recruiting
      • TG Therapeutics Investigational Trial Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • TG Therapeutics Investigational Trial Site
  • New York
    • New York, New York, United States, 10025
      • Recruiting
      • TG Therapeutics Investigational Trial Site
    • Rochester, New York, United States, 14642
      • Recruiting
      • TG Therapeutics Investigational Trial Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • TG Therapeutics Investigational Trial Site
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • TG Therapeutics Investigational Trial Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • TG Therapeutics Investigational Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.
5. 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:

1. Between age 18 and ≤ 75 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 ≤75 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 ≤75 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). Separately, Autoimmune Nodopathy (AN) participants with anti-CNTN1 or anti-NF155/anti-NF186, as confirmed by serological testing, may be included.
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. 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).

3. Viral and Tuberculosis (TB) Screening

   1. Evidence of chronic active or history of hepatitis B virus (HBV).
   2. Seropositive for human immunodeficiency virus (HIV) antibody.
4. History of bone marrow/hematopoietic stem cell or solid organ transplantation.
5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azer-cel; Participants will receive a single dose of intravenous (IV) infusion of azer-cel at different dose levels, on Day 0 of the treatment period.	Drug: Azercabtagene zapreleucel (azer-cel); IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Day 0 to Day 28

Secondary Outcome Measures

Outcome Measure	Time Frame
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 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 Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) Total Score	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
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

Collaborators and Investigators

• Sponsor: TG Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): September 9, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis (MS); Myasthenia Gravis (MG); Progressive forms of multiple sclerosis (PMS); Primary Progressive MS (PPMS); Secondary Progressive MS (SPMS); Neuromyelitis optica spectrum disorder (MNOSD); Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Polyneuropathies; Polyradiculoneuropathy; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
• Other Study ID Numbers: TG-Azercel-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No