A Phase 1 Study of ADI-001 in Autoimmune Disease

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 80 Years
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06375993
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Adicet Therapeutics
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

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

Arms

Experimental: ADI-001 Dose Escalation

ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001.

Experimental: ADI-001 Dose Extension

After dose level has been declared safe, additional patients can be enrolled at the declared safe dose to further investigate the safety profile of ADI-001.

Experimental: ADI-001 Dose Expansion

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Interventions

Drug: - ADI-001

Anti-CD20 CAR-T

Drug: - Fludarabine

Chemotherapy for Lymphodepletion

Drug: - Cyclophosphamide

Chemotherapy for Lymphodepletion

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Manhasset, New York

Status

Recruiting

Address

The Feinstein Institutes for Medical Research - Northwell Health

Manhasset, New York, 11030

Site Contact

Meggan Mackay, MD

[email protected]

516-562-3838