A Study of KITE-363 in Participants With Refractory Autoimmune Diseases

Phase 1

• Conditions: Systemic Lupus Erythematosus; Lupus Nephritis; Systemic Sclerosis; Idiopathic Inflammatory Myopathy
• Interventions: Biological: KITE-363; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT07038447
• Lead Sponsor: Kite, A Gilead Company

Brief Summary

This study will have two Phases: Phase 1a and Phase 1b. The goal of this clinical study is to learn more about the study drug KITE-363, to establish dosing, tolerability, safety, and preliminary efficacy of KITE-363 in participants with refractory autoimmune diseases.

The primary objectives of this study are:

Phase 1a: To evaluate the safety and tolerability of KITE-363 in participants with autoimmune disease. To determine the recommended dose for Phase 1b.

Phase 1b: To evaluate the safety and efficacy of KITE-363 in participants with autoimmune disease.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-06-18
• Study First Submitted QC: 2025-06-18
• Study First Posted: 2025-06-26
• Status Verified: 2025-07
• Study Start: 2025-07-02
• Last Update Submitted: 2025-07-11
• Last Update Posted: 2025-07-16
• Primary Completion: 2029-07
• Study Completion: 2029-07-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Inclusion Criteria for systemic lupus erythematosus (SLE) and lupus nephritis (LN):

• Age ≥ 18 and ≤ 75 years
• Meet the European Alliance of Associations for Rheumatology (EULAR)- American College of Rheumatology (ACR) 2019 classification criteria for SLE
• Presence of either double-stranded deoxyribonucleic acid (DNA) anti- double-stranded DNA (anti-dsDNA) and/or anti-Smith antibodies at screening per local laboratory.
• Moderate to severe, active disease defined as at least one British Isles Lupus Assessment Group (BILAG-A) score or 2 BILAG B (excluding constitutional and/or neuropsychiatric organ system).
• Refractory to steroids and inadequate response or intolerance to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, anifrolumab, rituximab, obinutuzumab, methotrexate, azathioprine, cyclosporin, tacrolimus, or voclosporin.
• For LN: Refractory to steroids and inadequate response or intolerance to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolate mofetil or its derivatives, belimumab, rituximab, obinutuzumab, azathioprine, cyclosporin, tacrolimus, or voclosporin

Inclusion Criteria for LN:

• Renal biopsy-proven Class III or intravenous (IV) ± V LN according to the revised International Society of Nephrology and Renal Pathology Society (ISN/RPS) criteria within 6 months prior to or during screening
• Evidence of active LN at screening

Inclusion Criteria for systemic sclerosis (SSc):

• Age ≥ 18 and ≤ 60 years
• Early systemic sclerosis according to ACR/EULAR 2013 classification criteria with active skin disease and/or progressive ILD
• Refractory or intolerance to 1 of the following for a minimum of 3 months and/or contraindication: mycophenolate mofetil or its derivatives, methotrexate, tocilizumab (or other IL-6 inhibitor), rituximab (or other B-cell depleting agent), nintedanib (or other antifibrotic agents), cyclophosphamide.
• High-resolution computer tomography (HRCT) scan and pulmonary function test (PFT) within 3 months prior to screening to evaluate for presence of SSc-ILD.

Inclusion Criteria for idiopathic inflammatory myopathy (IIM):

• Age ≥ 18 years
• IIM based on EULAR/ACR 2017 classification (excluding inclusion body myositis).
• Active disease demonstrated by electromyography (EMG). Magnetic resonance imaging (MRI) or muscle enzyme
• Moderate to severe disease activity
• Positive for myositis specific antibodies for patients with non-dermatomyostitis IIM
• HRCT scan and PFT within 3 months prior to screening to evaluate for presence of IIM-ILD.
• Refractory or intolerance to at least 1 month of glucocorticoids and standardized use of at least 2 immunosuppressant/modulator (eg, intravenous gamma globulins, methotrexate, mycophenolate mofetil and its derivatives, azathioprine, cyclophosphamide, calcineurin inhibitors, Janus kinase (JAK) inhibitors, rituximab or other B-cell depleting agent).

Inclusion Criteria for all Cohorts:

• Adequate hepatic, renal, pulmonary, and cardiac function.

Key

Exclusion Criteria

Exclusion Criteria for all Cohorts:

• Females of childbearing potential who are pregnant or breast feeding.
• Dialysis within the past year.
• History of malignancy, within the last 5 years.
• Hypogammaglobulinemia requiring immunoglobulin replacement.
• History of autologous or allogeneic stem cell transplant and/or organ transplant.
• Prior treatment with cellular therapy, gene therapy and/or T-cell engager therapy.
• Known history of HIV infection, or hepatitis B or C virus infections.
• Active or untreated latent tuberculosis (TB).
• Active or uncontrolled infections.
• Nonspecific, overlap, mixed autoimmune diseases not clearly identified into any of the studied cohorts.

Exclusion Criteria for LN:

• Significant pre-existing damage or rapidly progressive glomerulonephritis (GN).

Exclusion Criteria for SLE:

• Drug-induced SLE.
• Catastrophic antiphospholipid syndrome.
• Thrombotic thrombocytopenic purpura.
• Active or unstable lupus neuropsychiatric manifestations within last 6 months.

Exclusion Criteria for SSc:

• Digital ulceration or necrosis with infection.
• Severe pulmonary hypertension.
• History of systemic sclerosis renal crisis within 12 months prior to enrollment.
• History of active bleeding related to gastric antral vascular ectasia.

Exclusion Criteria for IIM:

• Other inflammatory and noninflammatory myopathies.
• Severe, irreversible muscle damage.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1a: KITE-363 (Dose Escalation)	KITE-363	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Phase 1a: KITE-363 (Dose Escalation)	Fludarabine	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Phase 1a: KITE-363 (Dose Escalation)	Cyclophosphamide	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by 2 dose escalations of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Phase 1b: KITE-363 (Dose Expansion)	KITE-363	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.
Phase 1b: KITE-363 (Dose Expansion)	Fludarabine	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.
Phase 1b: KITE-363 (Dose Expansion)	Cyclophosphamide	Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1ab recommended dose of KITE-363 CAR T cells.

Primary Outcome Measures

Name	Time	Method
Phase 1b: Lupus Nephritis (LN): Proportion of Participants Achieving a Complete Renal Response	Month 6
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363	Up to 2 years
Phase 1b: All Cohorts Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs)	Up to 2 years
Phase 1b: Systemic lupus erythematosus (SLE)/ Lupus Nephritis (LN): Proportion of Participants Meeting DORIS Remission and Lupus low Disease Activity State (LLDAS) Criteria at Month 6	Month 6
Phase 1b: Systemic Sclerosis (SSc) Cohort: Proportion of Participants with Improvement in Disease Activity by the Revised Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (rCRISS) at Month 6	Month 6
Phase 1b: Systemic Sclerosis (SSc) Cohort: Proportion of Participants With Progressive Interstitial Lung Disease (ILD), no Worsening of Pulmonary Function at Month 6	Month 6
Phase 1b: Idiopathic Inflammatory Myopathy: Proportions of Participants Meeting European League Against Rheumatism (EULAR)-American College of Rheumatology (ACR) Moderate and Major response 2016 Criteria in Total Improvement Score (TIS) at Month 6	Month 6

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameter: AUC for KITE-363 CAR T-cells	Up to 2 years	AUC is defined as the area under the concentration time curve for KITE-363 CAR T-cells.
Pharmacodynamic Parameters: Serum Concentration of Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors in blood over time	Up to 2 years
Pharmacodynamic Parameters: Peak Serum Concentration (Cmax) for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors	Up to 2 years
Pharmacodynamic Parameters: AUC for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors	Up to 2 years	AUC is defined as the area under the concentration time curve.
Pharmacodynamic Parameters: Time to Peak Serum Concentration (Tmax) for Pro-inflammatory and Immune-modulating Cytokines, Chemokines, and Effector molecules, Autoantibodies, Muscle Enzymes, and Complement factors	Up to 2 years
Percentage of Participants with Antibodies Against KITE-363 CAR T cells	Up to 2 years
Change from Baseline in Levels of B cells	Up to 2 years
Characterization of Product, Including T-cell Phenotype as Assessed by Percent Change From Baseline in cluster of differentiation 3 (CD3)+ Cells and T Cells	Baseline up to 2 years
Pharmacokinetic parameter: Serum Concentration of KITE-363 CAR T-cells	Up to 2 years
Pharmacokinetic parameter: Peak Concentration (Cmax) for KITE-363 CAR T-cells	Up to 2 years
Pharmacokinetic parameter: Time to Peak Serum Concentration (Tmax) for KITE-363 CAR T-cells	Up to 2 years

Trial Locations

Locations (1)

Concord Repatriation General Hospital; 🇦🇺 Syndey, New South Wales, Australia

Concord Repatriation General Hospital

🇦🇺Syndey, New South Wales, Australia