A Study to Evaluate the Safety and Preliminary Efficacy of ATA3219 in Participants With Systemic Lupus Erythematosus

NCT06429800 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: ATA3219-AEC-104
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety and preliminary efficacy of ATA3219 for treatment of participants with lupus nephritis (LN) following lymphodepletion (LD) and in participants with extrarenal systemic lupus erythematosus (SLE) without LD.

Conditions

Lupus Nephritis; Systemic Lupus Erythematosus

Keywords

Lupus Nephritis (LN); Systemic Lupus Erythematosus (SLE); Anti CD19 Chimeric Antigen Receptor T cell (CAR T) Therapy; Human leukocyte antigen (HLA); Epstein-Barr virus (EBV) T cells; Extrarenal Systemic Lupus Erythematosus (ERL)

Outcome Measures

Primary Outcomes (4)

• Number of Participants With treatment-emergent adverse events, including adverse events of special interest

  From administration of pretreatments (LD or methylprednisolone) through 90 days after administration of study drug

• Number of Participants With Dose-limiting Toxicities

  Day 1 through Day 28 of first dose of study drug

• Maximum Tolerated dose

  Day 1 through Day 28 of first dose of study drug

• Recommended Phase 2 dose of ATA3219

  Day 1 through Day 28 of first dose of study drug

Secondary Outcomes (22)

• Maximum Observed Plasma Concentration (Cmax) of ATA3219

  Pre-dose on Day 1 through 24 months after the last dose on a defined schedule

• Time to Reach Cmax (Tmax) of ATA3219

  Pre-dose on Day 1 through 24 months after the last dose on a defined schedule

• Partial Area Under the Curve (pAUC) of ATA3219

  Pre-dose on Day 1 through 24 months after the last dose on a defined schedule

• Last Observed Plasma Concentration (Clast) of ATA3219

  Pre-dose on Day 1 through 24 months after the last dose on a defined schedule

• Time of Clast of ATA3219

  Pre-dose on Day 1 through 24 months after the last dose on a defined schedule

Study Arms (8)

Cohort LN: ATA3219 Dose Level -1

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level -1 (if required) on Day 1 of a 28-day dose limiting toxicity (DLT) observation period.

Drug: ATA3219

Cohort LN: ATA3219 Dose Level 1

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 1 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort LN: ATA3219 Dose Level 2

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 2 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort LN: ATA3219 Dose Level 3

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 3 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort ERL: ATA3219 Dose Level -1

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level -1 (if required) on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort ERL: ATA3219 Dose Level 1

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 1 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort ERL: ATA3219 Dose Level 2

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 2 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Cohort ERL: ATA3219 Dose Level 3

EXPERIMENTAL

Participants will receive a single IV infusion of ATA3219 Dose Level 3 on Day 1 of a 28-day DLT observation period.

Drug: ATA3219

Interventions

ATA3219 DRUG

ATA3219 is an allogeneic chimeric antigen receptor (CAR) T-cell therapy containing a second generation CD19 CAR construct in Epstein Barr virus (EBV) T cells, administered intravenously on Day 1.

Cohort ERL: ATA3219 Dose Level -1; Cohort ERL: ATA3219 Dose Level 1; Cohort ERL: ATA3219 Dose Level 2; Cohort ERL: ATA3219 Dose Level 3; Cohort LN: ATA3219 Dose Level -1; Cohort LN: ATA3219 Dose Level 1; Cohort LN: ATA3219 Dose Level 2; Cohort LN: ATA3219 Dose Level 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification for SLE OR the Systemic Lupus International Collaborating Clinics Classification criteria \[Petri 2012\].
• Meets one or more of the following immunologic criteria during screening:
• Anti double stranded DNA above laboratory reference range, except enzyme linked immunosorbent assay (2 × above laboratory reference range), OR
• Presence of one or more of following autoantibodies: anti-Smith, anti-ribonucleoprotein, or anti-phospholipid, OR
• Low complement as demonstrated by low complement component 3, low complement component 4, or low complement CH50.
• Adequate lung, liver, kidney, and cardiac function.
• History of International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Class III or IV with or without Class V glomerulonephritis on renal biopsy either within 6 months prior to screening or as performed during screening. Biopsy should demonstrate evidence of active nephritis.
• Proteinuria level between ≥ 1.0 to 6.0 g/g via urine protein creatinine ratio during screening.
• Has refractory LN defined as having received 1 or more standard therapies for LN (which must have included mycophenolate mofetil, mycophenolic acid, or cyclophosphamide), and:
• Has worsening LN (per criteria listed in \[Gordon 2009\]) while on treatment, OR
• Has not achieved a complete renal response (CRR) after 2 or more lines of therapy, OR
• Has not achieved a CRR after first-line therapy after a minimum of 12 months.
• Hybrid SELENA-SLEDAI score of ≥ 8 points at screening
• For participants with BILAG A involvement, this must include "clinical" hybrid SELENA-SLEDAI score of ≥ 4 points
• For participants without BILAG A involvement, this must include clinical hybrid SELENA-SLEDAI score of ≥ 6 points

You may not qualify if:

• Has a concurrent systemic autoimmune disease that may confound study assessments other than SLE, LN, or cutaneous lupus erythematosus.
• Has any unstable or progressive manifestation of SLE that is likely to warrant an intensification of lupus-directed therapy
• Has a history of catastrophic antiphospholipid syndrome, or any history of prior thrombosis due to antiphospholipid syndrome resulting in hospitalization due to myocardial infarction, pulmonary embolism, or stroke.
• Has a history of bleeding disorder requiring hospitalization or systemic therapeutic intervention within the previous 3 months, or for participants without a prior kidney biopsy meeting eligibility criterion within the past 6 months who will require a biopsy during screening, any contraindication to kidney biopsy.
• Presence of clinically relevant (as assessed by the investigator) central nervous system (CNS) pathology such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; any BILAG A CNS manifestation within 4 weeks of enrollment.
• Any prior cellular therapies, obinutuzumab, anti-cluster of differentiation 19 (CD19) antibody, or B-cell targeting bispecific antibody, unless B-cells have recovered to baseline as assessed by the investigator. Investigational therapies or initiation of new SLE-directed therapies within 4 weeks.
• Severe kidney disease as assessed locally, defined as history of ISN/RPS Class VI or isolated Class V glomerulonephritis (without co existent/predominant Class III or IV glomerulonephritis) on renal biopsy.
• Known hypersensitivity to fludarabine or cyclophosphamide.
• Any inability to discontinue or taper systemic SLE therapy prior to infusion of ATA3219, including
• Tapering of corticosteroids to ≤ 10 mg/day and
• Discontinuation of other systemic SLE therapies (including mycophenolate and/or voclosporin)
• Severe kidney disease as assessed locally, defined as history of ISN/RPS Class III to IV on renal biopsy.
• Contraindication to methylprednisolone 500 mg daily for 2 days.
• Any inability to discontinue or taper systemic SLE therapy prior to infusion of ATA3219, including
• Tapering of corticosteroids to ≤ 20 mg/day by Day -2, and

Sponsors & Collaborators

• Atara Biotherapeutics: lead

Study Sites (1)

Atara Biotherapeutics

Thousand Oaks, California, 91320, United States

Location

Related Publications (2)

• Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.

  PMID: 22553077 BACKGROUND

• Gordon C, Jayne D, Pusey C, Adu D, Amoura Z, Aringer M, Ballerin J, Cervera R, Calvo-Alen J, Chizzolini C, Dayer J, Doria A, Ferrario F, Floege J, Guillevin L, Haubitz M, Hiepe F, Houssiau F, Lesavre P, Lightstone L, Meroni P, Meyer O, Moulin B, O'Reilly K, Praga M, Schulze-Koops H, Sinico R, Smith K, Tincani A, Vasconcelos C, Hughes G. European consensus statement on the terminology used in the management of lupus glomerulonephritis. Lupus. 2009 Mar;18(3):257-63. doi: 10.1177/0961203308100481.

  PMID: 19213865 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic; Epstein-Barr Virus Infections

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; Autoimmune Diseases; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Janal Urich

  Atara Biotherapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: May 28, 2024
• Study Start: April 16, 2025
• Primary Completion: April 16, 2025
• Study Completion: April 16, 2025
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)