A Phase 1 Study of ADI-001 in Autoimmune Disease

Phase 1

Recruiting

• Conditions: Lupus Nephritis; Idiopathic Inflammatory Myopathies; Autoimmune Diseases; Systemic Sclerosis (SSc); ANCA-Associated Vasculitis (AAV); Systemic Lupus Erythematosus (SLE); Stiff Person Syndrome
• Interventions: Drug: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT06375993
• Lead Sponsor: Adicet Therapeutics

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-17
• Study First Submitted QC: 2024-04-17
• Study First Posted: 2024-04-19
• Study Start: 2024-11-10
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-10
• Last Update Posted: 2025-01-13
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 180

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ADI-001 Dose Escalation	ADI-001	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.
ADI-001 Dose Extension	Fludarabine	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.
ADI-001 Dose Expansion	ADI-001	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
ADI-001 Dose Expansion	Cyclophosphamide	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
ADI-001 Dose Extension	ADI-001	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.
ADI-001 Dose Extension	Cyclophosphamide	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.
ADI-001 Dose Escalation	Fludarabine	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.
ADI-001 Dose Escalation	Cyclophosphamide	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.
ADI-001 Dose Expansion	Fludarabine	Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Primary Outcome Measures

Name	Time	Method
The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort	28 Days	This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD)
Proportion of treatment emergent and treatment related adverse events	2 year	This primary endpoint will be used to determine the MTD/MAD of ADI-001

Trial Locations

Locations (1)

The Feinstein Institutes for Medical Research - Northwell Health; 🇺🇸 Manhasset, New York, United States