[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06708845":3,"trial-entities:NCT06708845":136,"trial-summary:NCT06708845":143},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":23,"study_type":34,"primary_purpose":35,"phases":36,"enrollment_info":38,"interventions":41,"primary_outcomes":57,"secondary_outcomes":64,"sex":73,"minimum_age":74,"maximum_age":75,"healthy_volunteers":76,"eligibility_criteria":77,"std_ages":104,"locations":107,"central_contacts":122,"overall_officials":129,"references":134,"see_also_links":135},"NCT06708845","M-2024-423","US Zamto-cel Autoimmune Diseases","A Phase I Multicohort Trial of Zamtocabtagene Autoleucel (Zamto-Cel) in Subjects With Severe Refractory Autoimmune Diseases","RECRUITING","2028-07","2026-06","2026-06-11","2026-07","Miltenyi Biomedicine GmbH","INDUSTRY",true,"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\u002FdcSSc) after receiving standard therapy.","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 express CARs on their surfaces.\n\nEligible subjects will undergo leukapheresis for the collection of cells required for manufacturing. Prior to infusion of the fresh CAR-T product, subjects will receive a lymphodepleting regimen consisting of cyclophosphamide and fludarabine. The CAR-T cell infusion will be administered intravenously at a dose of 2.5 x 10\\^6 or 1.0 x 10\\^6 CAR+ cells\u002Fkg body weight, based on the dose level assigned to the cohort.\n\nThe study will initially enroll 3 subjects per cohort in a staggered manner to evaluate safety. Upon confirmation of safety, the study will proceed to cohort-specific recommended Phase 2 dose (RP2D) and dose expansion phases. Subjects will be monitored for up to 1 year to assess safety, preliminary efficacy, and health-related quality of life (HRQoL). Additional long-term follow-up will be conducted under a separate long-term follow-up protocol.",[19,20,21,22],"Lupus Nephritis","Systemic Lupus Erythematosus","Systemic Sclerosis (SSc)","Diffuse Cutaneous Systemic Sclerosis",[24,25,26,27,28,29,30,31,32,33],"Chimeric antigen receptor","CAR T","Zamtocabtagene autoleucel","Autoimmune Disease","Immune System Diseases","SLE-Non renal","SLE-LN","SSc","dcSSc","Lupus","INTERVENTIONAL","TREATMENT",[37],"PHASE1",{"count":39,"type":40},48,"ESTIMATED",[42,49,54],{"type":43,"name":44,"description":45,"armGroupLabels":46},"BIOLOGICAL","zamtocabtagene autoleucel","chimeric antigen receptor T-cell (CAR-T) therapy",[47,48],"Dose Level 1","Dose Level 2",{"type":50,"name":51,"description":52,"armGroupLabels":53},"DRUG","Cyclophosphamide","Lymphodepleting chemotherapy",[47,48],{"type":50,"name":55,"description":52,"armGroupLabels":56},"Fludarabine",[47,48],[58,61],{"measure":59,"timeFrame":60},"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",{"measure":62,"timeFrame":63},"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",[65,67,69,71],{"measure":66,"timeFrame":60},"The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)",{"measure":68,"timeFrame":60},"Clinical response at Week 4, 12, 24, and 52 evaluated by defined disease-specific activity measures in SLE-Non renal, SLE-LN, and SSc\u002FdcSSc",{"measure":70,"timeFrame":60},"The duration of remission or low disease activity status in respective diseases under the study",{"measure":72,"timeFrame":60},"Persistence, maximal drug concentration (Cmax), time to reach Cmax, area under the concentration curve, and phenotype of zamto-cel","ALL","18 Years",null,false,{"inclusion":78,"exclusion":92,"raw_text":103},[79,80,81,79,82,83,84,85,86,87,88,89,90,91],"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","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)","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:","Lack of response to standard therapy (e.g., failure of ≥ 2 immunosuppressive therapies)",[93,94,95,96,97,98,99,100,101,102],"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 \\\u003C 45 mL\u002Fmin\u002F1.73 m\\^2","Total bilirubin outside the normal range (unless congenital hyperbilirubinemia such as Gilbert syndrome has been confirmed).","Subjects with neuropsychiatric SLE.","Drug-induced SLE.","\"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","General Key Inclusion\u002FExclusion Criteria Across All Cohorts\n\nInclusion Criteria:\n\n•Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc\u002F dcSSc)\n\nExclusion Criteria:\n\n* Prior gene therapy treatment\n* Active malignancy within past 5 years\n* Significant active fungal or bacterial infection\n* History or presence of CNS lupus or other CNS disease\n* eGFR \\\u003C 45 mL\u002Fmin\u002F1.73 m\\^2\n* Total bilirubin outside the normal range (unless congenital hyperbilirubinemia such as Gilbert syndrome has been confirmed).\n\nSystemic Lupus Erythematosus-Non-renal Key Inclusion\u002FExclusion Criteria\n\nInclusion Criteria:\n\n* Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith\n* 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\n* 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\n\nExclusion Criteria:\n\n* Subjects with neuropsychiatric SLE.\n* Drug-induced SLE.\n\nSystemic Lupus Erythematosus - Lupus Nephritis Key Inclusion\u002FExclusion Criteria\n\nInclusion Criteria:\n\n* Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith\n* Confirmed LN diagnosis by kidney biopsy during screening or within the previous 6 months, with severe active phase of the disease.\n* Progressing despite maintenance on maximally tolerated doses of renin- angiotensin system (RAS) blocking agents, unless allergic to or intolerant of ACE inhibitors and ARBs\n* 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)\n\nExclusion Criteria:\n\n•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.\n\nSystemic Sclerosis\u002FDiffuse Cutaneous Systemic Sclerosis Cohort Key Inclusion\u002F Exclusion Criteria\n\nInclusion Criteria:\n\n* Active disease defined as:\n* Modified Rodnan skin score (mRSS) ≥ 16 units, in the prior 6 months, with 1 or more of the following:\n\n  * Increase in mRSS by ≥ 3 units or 10%\n  * Involvement of 1 new body area with increase in mRSS by ≥ 2 units\n  * Involvement of 2 new body areas with increase by ≥ 1 mRSS unit OR\n* Progressive interstitial lung disease (ILD) defined as:\n\n  \\- Worsening of respiratory symptoms and an increased extent of fibrosis evaluated by high-resolution computed tomography\n* Lack of response to standard therapy (e.g., failure of ≥ 2 immunosuppressive therapies)\n\nExclusion Criteria:\n\n* \"Active\" gastric antral vascular ectasia, as evidenced by bleeding (ie, on esophagogastroduodenoscopy) in the past 6 months or as per Investigator's assessment.\n* History of SSc renal crisis within 1 year prior to Screening; presence of kidney impairment due to conditions other than SSc",[105,106],"ADULT","OLDER_ADULT",[108],{"facility":109,"status":8,"city":110,"state":111,"zip":112,"country":113,"contacts":114,"geoPoint":119},"Froedtert Hospital and the Medical College of Wisconsin","Milwaukee","Wisconsin","53226","United States",[115],{"name":116,"role":117,"email":118},"Kiley Timler","CONTACT","ktimler@mcw.edu",{"lat":120,"lon":121},43.0389,-87.90647,[123,127],{"name":124,"role":117,"phone":125,"email":126},"Sadie Swift","617-218-0044","clinicaltrials@miltenyi.com",{"name":128,"role":117,"phone":125,"email":126},"Paris Jamiel",[130],{"name":131,"affiliation":132,"role":133},"Esther Eromosele, MD","Miltenyi Biomedicine","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":137,"biomarkers":140},[22,138,20,139],"Lupus Glomerulonephritis","Systemic Scleroderma",[141,142],"Anti-Double Stranded DNA Measurement","anti-Smith",{"nct_id":4,"found":76,"summary":75,"prompt_version":75}]