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
Trial Snapshot
- Phase
- Phase 1
- Status
- Enrolling By Invitation
- Sponsor
- Kite, A Gilead Company
- Enrollment
- 52
- Locations
- 13
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non-randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None (open label)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 autoantibodies as specified in the protocol
- 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.
Arms & Interventions
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1a recommended dose of KITE-363 CAR T cells.
Intervention: Cyclophosphamide (Drug)
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy followed by different doses of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Intervention: Cyclophosphamide (Drug)
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1a recommended dose of KITE-363 CAR T cells.
Intervention: KITE-363 (Biological)
Phase 1b: KITE-363 (Dose Expansion)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1a recommended dose of KITE-363 CAR T cells.
Intervention: Fludarabine (Drug)
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy followed by different doses of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Intervention: Fludarabine (Drug)
Phase 1a: KITE-363 (Dose Escalation)
Participants with refractory autoimmune diseases will receive lymphodepleting chemotherapy followed by different doses of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells to find the Phase 1b recommended dose.
Intervention: KITE-363 (Biological)
Outcomes
Primary Outcomes
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: 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: 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
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
Secondary Outcomes
- 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: AUC 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)
- 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)
- 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)
Investigators
Study Sites (13)
Identifiers
- NCT ID
- NCT07038447
- Other Study IDs
- KT-US-720-0203
Dates
- First Submitted
- (last year)
- First Posted
- (last year)
- Primary Completion
- (in 3 years)
- Study Completion
- (in 3 years)
- Last Verified
- (29 days ago)
- Last updated
- (2 days ago)
Regulatory & Sharing
- FDA Regulated Drug
- Yes
- FDA Regulated Device
- No
- IPD Sharing Plan
- No
- Has Results
- No