a phase 1 study of adi-001 in autoimmune disease

Conditions: Lupus Nephritis; Autoimmune Diseases; Systemic Sclerosis (SSc); Systemic Lupus Erythematosus (SLE); ANCA-Associated Vasculitis (AAV); Idiopathic Inflammatory Myopathies; Stiff Person Syndrome

Summary: adi-202300103 is a phase 1 multicenter, open label, dose finding and dose expansion, safety/efficacy study in patients with autoimmune disease. the study will consist of different periods including screening, lymphodepletion, treatment, and follow-up


Eligibility criteria:
inclusion criteria: for cohort 1: subjects with ln: 1. clinical diagnosis of systemic lupus erythematosus (sle) per 2019 european league against rheumatism (eular)/american college of rheumatology (acr) classification criteria (aringer 2019) 2. active kidney disease with biopsy-proven active ln class iii or iv (coexistent class v permitted) (per 2018 international society of nephrology \[isn\]/renal pathology society \[rps\] criteria); biopsy should be performed within 6 months before enrolling in the study 3. ecog performance ≤ 2 4. proteinuria (or urine protein creatinine ratio \[upcr\]) \> 1g / 24 hours for cohort 1: subjects with sle with extrarenal involvement 1. clinical diagnosis of systemic lupus erythematosus (sle) per 2019 european league against rheumatism (eular)/american college of rheumatology (acr) classification criteria (aringer 2019). 2. systemic lupus erythematosus disease activity index 2000 (sledai-2k) score ≥ 8 with a clinical sledai-2k score (sledai-2k not including points for anti-dsdna and/or low complement) ≥ 6 and/or ≥ 1 british isles lupus assessment group (bilag)-2004 category a 3. positive anti-nuclear antibody (ana) test results and/or a positive anti-dsdna and/or anti-smith antibodies above the uln 4. estimated creatinine clearance ≥ 60 ml/min 5. inadequate response in terms of active disease despite treatment with current standard of care for sle including corticosteroids and at least 2 sle therapy for cohort 2: subjects with ssc 1. disease duration ≤ 6 years (from onset of first non-raynaud manifestation) 2. participants with diffuse cutaneous ssc with worsening skin disease, must meet both of the following criteria: mrss ≥ 15 at screening and one of the following within 6 months prior to screening: (i) mrss increase of ≥ 3 units in the total mrss, or (ii) involvement of 1 new body area, or (iii) increase in mrss ≥ 2 units in 1 body area 3. participants with diffuse or limited cutaneous ssc and ild must meet both of the following criteria: ild, i.e. fibrosis on hrct within 4 months of screening and progression of ild by fvc or hrct in previous 24 months 4. fvc ≥ 45% predicted, dlco ≥ 40% 5. exclude pah defined as rvsp ≥ 45 mmhg or right atrial or ventricular enlargement or dilatation, or renal crisis within 1 year of enrollment for cohort 3: subjects with aav 1. diagnosis of aav defined as either gpa or mpa according to the 2012 chapel hill consensus conference 2. positive for pr3-anca or mpo-anca 3. relapsed or refractory aav after at least 1 standard-of-care immunosuppressive regimen in addition to steroids. 4. severe disease (i.e., presence of one or more major aav sign or symptom per the bvas or ≥ 3 minor items, or at least the 2 renal items of proteinuria and hematuria due to vasculitis) 5. adequate renal function: crcl ≥ 30 ml/min 6. proteinuria ≤ 8 g/24 hour for cohort 4: subjects with idiopathic inflammatory myopathies 1. meets the 2017 acr/eular classification criteria (lundberg 2017) for probable/definite iim 2. muscle weakness defined as manual muscle testing (mmt)-8 score \ 0.25 , (iv) extra-muscular global activity vas ≥ 2 cm (10-cm vas) 3. active disease defined as ≥ 1 of the following signs in the past 4 months: a) elevated serum ck or aldolase levels ≥ 3 times uln; b) active myositis by muscle biopsy, muscle mri, or emg; c) active dm rash and cdasi \>14; d) active interstitial lung disease 4. positivity for ≥ 1 myositis-specific antibody or myositis-associated antibody at screening 5. inadequate response or intolerance/contraindication to glucocorticoids and to ≥ 2 immunosuppressants for 3 months/drug for cohort 4: subjects with stiff person syndrome 1. meets the 2009 criteria for diagnosis of stiff person syndrome (sps) (dalakas 2009): (a) stiffness of the axial muscles, particularly the abdominal and thoraco-lumbar paraspinals, leading to hyperlordosis; (b) superimposed painful spasms triggered by unexpected tactile or auditory stimuli; (c) severe anxiety with task-specific phobias especially in anticipation of physically challenging tasks; (d) electromyographic evidence of continuous motor unit activity of agonist and antagonist muscles; (e) absence of other neurological findings that may suggest an alternative diagnosis; (f) highly positive anti-gad titer (\> 10,000 iu/ml in serum by elisa or detectable in csf) 2. inadequate response or intolerance or contraindication to ≥ 1 treatment including chronic ivig or other biologic exclusion criteria: for all subjects: 1. presence of severe liver disease, child-pugh class b or c. 2. prior treatment with any gene therapy, genetically modified cell therapy, or adoptive t cell therapy. 3. autoimmune disease requiring prednisone higher than 0.5 mg/kg/day (or corticosteroid equivalent). 4. subjects unwilling to participate in an extended safety monitoring period (ltfu protocol) 5. history of a clinically significant infection (including sepsis, pneumonia, bacteremia, fungal, viral and opportunistic infections) within 4 weeks prior to first dose of study drug which in the opinion of the investigator may compromise the safety of the subject in the study.