B-cell Mediated Autoimmune Disorders
Conditions
Keywords
Progressive forms of multiple sclerosis (PMS), Primary Progressive MS (PPMS), Secondary Progressive MS (SPMS), Multiple Sclerosis (MS), Neuromyelitis optica spectrum disorder (MNOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
Brief summary
The main objective of the study is to determine the recommended phase 2 dose (RP2D) of Azercabtagene zapreleucel (azer-cel).
Interventions
DRUGAzercabtagene zapreleucel (azer-cel)
IV infusion
Sponsors
TG Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Dose-Limiting Toxicities (DLTs) | 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. |
Secondary
| 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 |
Countries
United States
Contacts
CONTACTTG Therapeutics Clinical Support Team
Outcome results
None listed