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

Official title

A Phase 1 Open-label, Multiregional, Multicenter, Basket Study Evaluating the Safety and Efficacy of KITE-363, an Autologous Anti-CD19/CD20 CAR T-cell Therapy in Participants With Refractory Autoimmune Diseases

Overview

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.

Interventions

• Biological KITE-363
  A single infusion of CAR-transduced autologous T cells administered intravenously
• Drug Fludarabine
  Administered intravenously
• Drug Cyclophosphamide
  Administered intravenously

Primary outcome measures

• Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 [Time frame: Up to 2 years]
• Phase 1b: All Cohorts Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs) [Time frame: 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 [Time frame: Month 6]
• Phase 1b: Lupus Nephritis (LN): Proportion of Participants Meeting DORIS Remission [Time frame: Month 6]
• Phase 1b: LN: Proportion of Participants Achieving a Complete Renal Response at Month 6 [Time frame: 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 [Time frame: 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 [Time frame: Month 6]

Secondary outcome measures (11)

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

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• City of Hope — Duarte
• Stanford University — Stanford
• Tampa General Hospital Cancer Institute — Tampa
• Icahn School of Medicine at Mount Sinai — New York

Australia · 2 centers

• Concord Repatriation General Hospital — Syndey
• St Vincent's Hospital — Fitzroy

Canada · 2 centers

• Jewish General Hospital — Montreal
• The Ottawa Hospital, General Campus — Ottawa

Identifiers

NCT: NCT07038447 · KT-US-720-0203

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗