US Zamto-cel Autoimmune Diseases
- Conditions
- Interventions
- Registration Number
- NCT06708845
- Lead Sponsor
- Miltenyi Biomedicine GmbH
- Brief Summary
AID is a phase I multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (SLE-Non renal, SLE-LN, SSc/dcSSc) after receiving standard therapy.
- Detailed Description
This is a Phase 1, multicohort, dose-finding study evaluating autologous T cells engineered to target dual CD19 and CD20 antigens in subjects with refractory autoimmune diseases following standard therapy. The investigational product, Zamto-cel, is a chimeric antigen receptor T-cell (CAR-T) therapy genetically engineered to enable subjects' T cells to expres...
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 48
•Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc/ dcSSc)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Level 1 zamtocabtagene autoleucel - Dose Level 1 Cyclophosphamide - Dose Level 1 Fludarabine - Dose Level 2 zamtocabtagene autoleucel - Dose Level 2 Cyclophosphamide - Dose Level 2 Fludarabine -
- Primary Outcome Measures
Name Time Method The incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) From enrollment through study completion 12 months post zamto-cel infusion The proportion of subjects with dose-limiting toxicities (DLTs) up to Day 28 and determination of recommended Phase 2 dose (RP2D) From enrollment through Day 28 post zamto-cel infusion
- Secondary Outcome Measures
Name Time Method The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) From enrollment through study completion 12 months post zamto-cel infusion Clinical response at Week 4, 12, 24, and 52 evaluated by defined disease-specific activity measures in SLE-Non renal, SLE-LN, and SSc/dcSSc From enrollment through study completion 12 months post zamto-cel infusion The duration of remission or low disease activity status in respective diseases under the study From enrollment through study completion 12 months post zamto-cel infusion Persistence, maximal drug concentration (Cmax), time to reach Cmax, area under the concentration curve, and phenotype of zamto-cel From enrollment through study completion 12 months post zamto-cel infusion