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

TG Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: B-cell Mediated Autoimmune Disorders

Treatments: Drug: Azercabtagene zapreleucel (azer-cel)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06680037

TG-Azercel-101

Details and patient eligibility

About

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

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Azer-cel

Experimental group

Description:

Participants will receive a single dose of intravenous (IV) infusion of azer-cel at different dose levels, on Day 0 of the treatment period.

Treatment:

Drug: Azercabtagene zapreleucel (azer-cel)