RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase 1 Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma-Delta (γδ) T Cells in Adults with Autoimmune Disease

Quick Facts

Study Start:2024-11-10

Study Completion:2027-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06375993

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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 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 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 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 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 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	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.

Inclusion Criteria

Exclusion Criteria

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
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
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
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
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
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

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.

Contacts and Locations

Study Contact

Adicet Medical Director

CONTACT

650-503-9095

clinicaltrials@adicetbio.com

Study Locations (Sites)

The Feinstein Institutes for Medical Research - Northwell Health

Manhasset, New York, 11030

United States

Collaborators and Investigators

Sponsor: Adicet Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-11-10

Study Completion Date2027-12

Study Record Updates

Study Start Date2024-11-10

Study Completion Date2027-12

Terms related to this study

Additional Relevant MeSH Terms

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