KITE-363: A single infusion of CAR-transduced autologous T cells administered intravenously
Fludarabine: Administered intravenously
Cyclophosphamide: Administered intravenously
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria:
Inclusion Criteria for systemic lupus erythematosus (SLE) and lupus nephritis (LN):
* Age ≥ 18 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 years
* Diffuse Systemic Sclerosis (SSc) according to ACR/EULAR 2013 classification criteria with active skin disease and/or progressive SSc-interstitial lung disease (ILD) OR limited SSc with 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.
Inclusion Criteria for idiopathic inflammatory myopathy (IIM):
* Age ≥ 18 years
* Probable or definite IIM based on EULAR/ACR 2017 classification (excluding inclusion body myositis).
* Active disease demonstrated by electromyography (EMG), magnetic resonance imaging (MRI) or muscle enzymes
* 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.
* 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:
* Infected digital ulceration or necrosis with signs of 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.
Primary outcome measure(s)
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): Proportion of participants meeting DORIS remission and Lupus low Disease Activity State (LLDAS) criteria at Month 6 — Month 6
Phase 1b: LN: Proportion of Participants Achieving a Complete Renal Response 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: Idiopathic Inflammatory Myopathy (IIM): 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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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