A Phase 1 Study of Prulacabtagene Leucel (Prula-cel, Formerly ADI-001) in Autoimmune Disease

Inclusion Criteria

• •For Cohort 1: Subjects with LN:
• •Clinical diagnosis of systemic lupus erythematosus (SLE) per 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aringer 2019).
• •Have unequivocally positive anti-nuclear antibody (ANA) test results defined as an ANA titer ≥ 1:80 (based on Hep-2 immunofluorescence assay or equivalence by enzyme-linked immunosorbent assay (ELISA), and/or positive anti-dsDNA (≥ 30 IU/mL based on ELISA.
• •Historical ANA and anti-dsDNA results (defined as within the 2 years prior to enrollment) may be used for eligibility. During screening a specimen will be collected.
• •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.
• •Proteinuria (or urine protein creatinine ratio \[UPCR\]) \> 1g / 24 hours.
• •LN showing inadequate response to current standard of care, defined per 2023 EULAR/ERA-EDTA recommendations as:
• •Failure following at least two lines of standard of care therapies for LN (including at least one being mycophenolate or cyclophosphamide or a biologic at doses and durations of treatment per local standard of care.
• •Adequate renal function, including:
• •Estimated creatinine clearance ≥ 45 mL/min as calculated using the method standard for the institution, or equivalent estimated glomerular filtration rate (eGFR) determination.
• •Proteinuria ≤ 8 g/24 h or UPCR ≤ 8 in a spot urine.
• •Adequate pulmonary function defined saturated oxygen (SpO2) ≥ 93% on room air.
• •For Cohort 1: Subjects with SLE with Extrarenal Involvement
• •Clinical diagnosis of systemic lupus erythematosus (SLE) per 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria (Aringer 2019).
• •Positive anti-nuclear antibody (ANA) test results and/or a positive anti-dsDNA and/or anti-Smith antibodies above the ULN.
• •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 AND physician's global assessment of SLE disease activity score ≥ 1.5 (on a 0 to 3 visual analogue scale).
• •Inadequate response in terms of active disease despite treatment with current standard of care for SLE including corticosteroids and at least 2 SLE therapy.
• •Estimated creatinine clearance ≥ 60 mL/min AND Proteinuria ≤ 1 g/24 h or UPCR ≤ 1 in a spot urine.
• •Adequate pulmonary function defined saturated oxygen (SpO2) ≥ 93% on room air.
• •For Cohort 2: Subjects with SSc
• •Disease duration ≤ 6 years (from onset of first non-Raynaud manifestation)
• •Subjects with diffuse cutaneous SSc, 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
• •Subjects with diffuse or limited cutaneous SSc and ILD must meet both of the following criteria: ILD, defined as evidence of fibrosis on HRCT within 4 months of screening AND Progression of ILD by FVC or HRCT in previous 24 months:
• •Relative decline in FVC of 10% predicted or more OR 5% to \<10% and worsening respiratory symptoms OR relative decline in FVC of 5% to \<10% and any increased extent of fibrosis on HRCT OR Worsening of respiratory symptoms and any increased extent of fibrosis on HRCT.
• •Inadequate response to at least one (1) of the following medications administered at the appropriate dose for at least 3 months within 24 months prior to screening: mycophenolate mofetil or its derivatives, cyclophosphamide, tocilizumab, rituximab, azathioprine, methotrexate.
• •Adequate pulmonary function, defined as Baseline FVC ≥ 45% predicted AND Baseline diffusing capacity of the lung for carbon monoxide (DLCO), corrected for hemoglobin, ≥ 40% predicted.
• •Adequate renal function, defined as Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 as estimated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Inker 2021).
• •For Cohort 3: Subjects with AAV
• •Diagnosis of AAV defined as either GPA or MPA according to the 2012 Chapel Hill Consensus Conference definitions:
• •Positive for PR3-ANCA or MPO-ANCA
• •Relapsed or refractory AAV:
• •Relapsed following remission after at least 1 standard-of-care immunosuppressive regimen in addition to steroids.
• •Refractory after at least 1 immunosuppressive regimen in addition to steroids administered for at least 3 months.
• •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)
• •Adequate renal function: CrCl ≥ 30 mL/min AND Proteinuria ≤ 8 g/24 hour or UPCR ≤ 8 in a spot urine.
• •Adequate pulmonary function defined as saturated oxygen (SpO2) ≥ 93% on room air.
• •For Cohort 4: Subjects with Idiopathic Inflammatory Myopathies
• •Meets the 2017 ACR/EULAR classification criteria (Lundberg 2017) for probable/definite IIM
• •Muscle weakness defined as Manual Muscle Testing (MMT)-8 score \< 142/150, and ≥ 2 of the following abnormal core set measures: (i) Patient global assessment VAS ≥ 2 cm (on 10-cm VAS), (ii) Physician global assessment VAS ≥ 2 cm (10-cm VAS), (iii) HAQ-DI \> 0.25 , (iv) Extra-muscular global activity VAS ≥ 2 cm (10-cm VAS)
• •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
• •Positivity for ≥ 1 myositis-specific antibody or myositis-associated antibody at screening
• •Inadequate response or intolerance/contraindication to glucocorticoids and to ≥ 2 immunosuppressants for 3 months of an immunosuppressive medication.
• •Adequate renal function defined as estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 as estimated by the 2021 CKD-EPI equation.
• •For Cohort 4: Subjects with Stiff Person Syndrome
• •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)
• •Inadequate response or intolerance or contraindication to ≥ 1 treatment including chronic IVIG or other biologic therapy.