A Phase 1 Study of ADI-001 in Autoimmune Disease

Launched by ADICET THERAPEUTICS · Apr 17, 2024

Keywords

ClinConnect Summary

This clinical trial is testing a new treatment called ADI-001 for patients with lupus nephritis, a kidney problem that can occur in people with lupus, an autoimmune disease. The goal of this study is to find the right dose of this treatment and to see how safe and effective it is for managing kidney disease related to lupus. The trial is currently looking for participants, and people aged between 18 and 75 who have been diagnosed with systemic lupus erythematosus and have active kidney disease may be eligible to join. Participants should have had a kidney biopsy within the last six months that confirms their condition.

If you decide to take part in this trial, you'll go through several stages, including screening, a process to prepare your body for treatment, the treatment itself, and follow-up visits to monitor your health. It's important to note that certain health issues, like severe liver disease or other autoimmune diseases, may prevent someone from participating. This study represents a valuable opportunity for those looking for new options in managing lupus nephritis, and it aims to contribute to the understanding of this condition and its treatments.

Gender

ALL

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 \< 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)
• • 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.