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

NCT06375993 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: ADI-202300103
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort

  This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD)

  28 Days

• Proportion of treatment emergent and treatment related adverse events

  This primary endpoint will be used to determine the MTD/MAD of ADI-001

  2 year

Study Arms (3)

ADI-001 Dose Escalation

EXPERIMENTAL

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.

Drug: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

ADI-001 Dose Extension

EXPERIMENTAL

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. Dose extension patients will not contribute to the determination of MTD/MAD and DLT evaluation.

Drug: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

ADI-001 Dose Expansion

EXPERIMENTAL

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

Drug: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

ADI-001 DRUG

Anti-CD20 CAR-T

ADI-001 Dose Escalation; ADI-001 Dose Expansion; ADI-001 Dose Extension

Fludarabine DRUG

Chemotherapy for Lymphodepletion

ADI-001 Dose Escalation; ADI-001 Dose Expansion; ADI-001 Dose Extension

Cyclophosphamide DRUG

Chemotherapy for Lymphodepletion

ADI-001 Dose Escalation; ADI-001 Dose Expansion; ADI-001 Dose Extension

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• For all Subjects:
• Presence of severe liver disease, Child-Pugh class B or C.
• Prior treatment with any gene therapy, genetically modified cell therapy, or adoptive T cell therapy.
• Autoimmune disease requiring prednisone higher than 0.5 mg/kg/day (or corticosteroid equivalent).
• Subjects unwilling to participate in an extended safety monitoring period (LTFU protocol)
• 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.
• Radiation therapy within 1 week prior to study entry.
• Autologous stem cell transplant (auto-SCT) within 6 weeks of planned prulacabtagene leucel (prula-cel) infusion.
• History of any form of primary immunodeficiency such as severe combined immunodeficiency disease.
• History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac diseases.
• Concurrent malignancy or history of prior malignancy requiring systemic treatment. Subjects with a prior history of malignancy whose natural history or treatment does not have the potential to interfere with either the safety or efficacy assessment of the investigational regimen may be included after discussion with Sponsor or designee.
• Active acute or chronic graft-versus-host disease (GvHD) other than Grade 1 with skin involvement, or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment.
• Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or that, in the judgment of the investigator, would make the subject inappropriate for entry into the study.
• Concurrent opportunistic infections.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study, including known hypersensitivity reaction to dimethyl sulfoxide (DMSO) or excipients of cell therapy products.

Sponsors & Collaborators

• Adicet Therapeutics: lead

Study Sites (2)

Adicet Clinical Trials

Redwood City, California, 94065, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Lupus Nephritis; Autoimmune Diseases; Scleroderma, Systemic; Lupus Erythematosus, Systemic; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Myositis; Stiff-Person Syndrome

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Skin Diseases; Systemic Vasculitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Autoimmune Diseases of the Nervous System; Spinal Cord Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 Dose Escalation Design

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: April 19, 2024
• Study Start: November 10, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

US (2)