Zamtocabtagene Autologous CAR-T for Autoimmune Diseases

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a Phase 1, multicohort, dose-finding study evaluating autologous CAR-T cells engineered to target CD19 and CD20 for autoimmune diseases that have not responded to standard therapies. Participants undergo leukapheresis to collect cells, receive a lymphodepleting regimen, and then are infused with zamto-cel at specified dose levels. The study prioritizes safety in initial cohorts before expanding to defined dose levels and assessing preliminary signs of efficacy and quality of life over up to one year. Long-term follow-up will occur under a separate protocol.

Why it matters

Who can join: the full rules

General Key Inclusion/Exclusion Criteria Across All Cohorts

Inclusion Criteria:

•Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc/ dcSSc)

Exclusion Criteria:

* Prior gene therapy treatment
* Active malignancy within past 5 years
* Significant active fungal or bacterial infection
* History or presence of CNS lupus or other CNS disease
* eGFR \< 45 mL/min/1.73 m\^2
* Total bilirubin outside the normal range (unless congenital hyperbilirubinemia such as Gilbert syndrome has been confirmed).

Systemic Lupus Erythematosus-Non-renal Key Inclusion/Exclusion Criteria

Inclusion Criteria:

* Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith
* Systemic Lupus Erythematosus Disease Activity Index-2000 score ≥ 8 AND at least 1 British Isles Lupus Assessment Group (BILAG)-2004 Class A (severe manifestation) organ scores
* Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, or obinutuzumab

Exclusion Criteria:

* Subjects with neuropsychiatric SLE.
* Drug-induced SLE.

Systemic Lupus Erythematosus - Lupus Nephritis Key Inclusion/Exclusion Criteria

Inclusion Criteria:

* Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith
* Confirmed LN diagnosis by kidney biopsy during screening or within the previous 6 months, with severe active phase of the disease.
* Progressing despite maintenance on maximally tolerated doses of renin- angiotensin system (RAS) blocking agents, unless allergic to or intolerant of ACE inhibitors and ARBs
* Inadequate response to glucocorticoids and hydroxychloroquine and at least 1 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid derivatives, belimumab, azathioprine, methotrexate, rituximab, obinutuzumab, calcineurin inhibitor (cyclosporin, tacrolimus or voclosporin)

Exclusion Criteria:

•Evidence of Rapidly progressive glomerulonephritis (defined as a doubling of serum creatinine within 3 months prior to enrollment) or as determined by the study investigator.

Systemic Sclerosis/Diffuse Cutaneous Systemic Sclerosis Cohort Key Inclusion/ Exclusion Criteria

Inclusion Criteria:

* Active disease defined as:
* Modified Rodnan skin score (mRSS) ≥ 16 units, in the prior 6 months, with 1 or more of the following:

  * Increase in mRSS by ≥ 3 units or 10%
  * Involvement of 1 new body area with increase in mRSS by ≥ 2 units
  * Involvement of 2 new body areas with increase by ≥ 1 mRSS unit OR
* Progressive interstitial lung disease (ILD) defined as:

  \- Worsening of respiratory symptoms and an increased extent of fibrosis evaluated by high-resolution computed tomography
* Lack of response to standard therapy (e.g., failure of ≥ 2 immunosuppressive therapies)

Exclusion Criteria:

* "Active" gastric antral vascular ectasia, as evidenced by bleeding (ie, on esophagogastroduodenoscopy) in the past 6 months or as per Investigator's assessment.
* History of SSc renal crisis within 1 year prior to Screening; presence of kidney impairment due to conditions other than SSc

Where it's running

• Froedtert Hospital and the Medical College of Wisconsin
  Milwaukee, Wisconsin, United States Recruiting

Study contacts

• Study coordinator: Sadie Swift
• Email: clinicaltrials@miltenyi.com
• Phone: 617-218-0044

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• ATG-201 in adults with autoimmune diseases

  This early, open-label study tests ATG-201 in adults with autoimmune diseases to see if it is safe and tolerable, and to get initial clues about how the body handles the drug and its effects.

  Recruiting Phase 1 Antengene Corporation · Bengbu, Anhui and 21 other locations · NCT07732309

• Biomarker tests in adults with lupus to see how kidney disease changes over time

  Researchers will follow adults with lupus to see if blood and urine biomarkers can predict kidney involvement, flares, and treatment responses during routine care.

  Recruiting Oslo University Hospital · Oslo, Oslo · NCT07666711

• Mosunetuzumab for people with systemic lupus erythematosus

  This study tests mosunetuzumab in people with systemic lupus erythematosus, with or without active lupus nephritis.

  Recruiting at 24 sites Phase 2 Hoffmann-La Roche · CABA, Buenos Aires and 23 other locations · NCT07598396

• FT819 in Lupus Nephritis: a targeted cell therapy trial for moderate-to-severe LN

  This trial tests whether FT819, a donor-derived CAR T cell therapy, can help people with difficult-to-treat lupus nephritis who have not responded to other medicines.

  Recruiting at 12 sites Phase 2 Fate Therapeutics · Beverly Hills, California and 11 other locations · NCT07570862

• MTS109 treatment for refractory autoimmune diseases

  This trial tests whether MTS109 (an mRNA-LNP given by subcutaneous injection) is safe and tolerable in adults with moderate to severe autoimmune diseases that have not responded to standard treatments.

  Recruiting Early Phase 1 Shanghai Changzheng Hospital · Shanghai, Shanghai Municipality · NCT07526350

• Using long-lived immune cells to calm an overactive immune system

  This trial will try QEL-005, an autologous CD19-directed CAR-T regulatory cell therapy, to calm immune overactivity in adults with diffuse cutaneous systemic sclerosis or difficult-to-treat rheumatoid arthritis.

  Recruiting at 7 sites Phase 1/2 Quell Therapeutics Limited · Düsseldorf and 9 other locations · NCT07473154

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.