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 Relapsed/Refractory Autoimmune Neurologic Diseases
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Kite, A Gilead Company
- Enrollment
- 52
- Locations
- 3
- Primary Endpoint
- Phase 1b: Progressive Forms of MS (PPMS) and (naSPMS): Time to Onset of Confirmed Disability Progression Over 12 Weeks (CDP-12)
Overview
Brief Summary
This study will have two Phases: Phase 1a and Phase 1b. The goals of this clinical study are to learn more about the study drug KITE-363, by evaluating its safety, tolerability and efficacy in participants with relapsed/refractory autoimmune neurologic diseases.
The primary objectives of this study are:
- To evaluate the safety and tolerability of KITE-363 in participants with autoimmune neurologic diseases
- To determine the recommended dose for Phase 1b.
- To evaluate the preliminary efficacy of KITE-363 in participants with autoimmune neurologic diseases.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Reproductive status-related eligibility and contraception requirements:
- •Participants must agree to use protocol-specified method(s) of contraception where applicable
- •Inclusion Criteria for multiple sclerosis (MS):
- •MS (Relapsing and progressive forms):
- •Diagnosed with MS according to the 2017 revision of the McDonald diagnostic criteria
- •Relapsing forms of MS (relapsing-remitting multiple sclerosis (RRMS), active secondary-progressive multiple sclerosis (aSPMS)):
- •Inadequate response to previous therapies is defined as evidence of breakthrough disease activity within 12 months prior to screening while on high efficacy disease-modifying therapy (DMT) OR Inadequate response to previous therapies defined as intolerance to ≥ 2 DMTs due to side effects prohibiting the chronic use of the DMT.
- •Expanded Disability Status Scale (EDSS) 0 to 5.5
- •Progressive forms of MS (primary-progressive multiple sclerosis (PPMS) and non-active secondary-progressive multiple sclerosis (naSPMS)):
- •Inadequate response to previous therapies is defined as evidence of disease progression within 12 months prior to screening despite standard of care therapy for naSPMS or despite ocrelizumab, where available, for PPMS
Exclusion Criteria
- •History or presence of central nervous system (CNS) or peripheral nervous system disorders before enrollment that may impact cognition, strength, or cause weakness
- •History of autologous or allogeneic stem cell transplant and/or organ transplant
- •Exclusion Criteria for MS:
- •Cohort 1 or 2; inability to complete 9-hole Peg Test (9-HPT) in \< 240 seconds and Timed 25 foot Walk (T25FW) \< 150 seconds
- •History of hypersensitivity to parenteral administration of gadolinium-based contrast agents
- •Any renal condition that would preclude the administration of gadolinium (for the relapsing forms of MS and progressive forms of MS)
- •Any contraindication to lumbar puncture (LP) (for the relapsing forms of MS and progressive forms of MS)
- •Exclusion Criteria for MG:
- •Current myasthenic crisis not effectively controlled within 2 weeks before enrollment
- •Thymectomy performed within 12 months of baseline
Arms & Interventions
Phase 1a: KITE-363 (Dose Escalation)
Participants with relapsing forms of multiple sclerosis (RMS), progressive forms of multiple sclerosis (PMS), myasthenia gravis (MG), and/or chronic inflammatory demyelinating polyneuropathy (CIDP) will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by infusion of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells at a single dose level, with different participants receiving sequential dose-escalation levels to find the Phase 1b recommended dose.
Intervention: KITE-363 (Biological)
Phase 1a: KITE-363 (Dose Escalation)
Participants with relapsing forms of multiple sclerosis (RMS), progressive forms of multiple sclerosis (PMS), myasthenia gravis (MG), and/or chronic inflammatory demyelinating polyneuropathy (CIDP) will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by infusion of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells at a single dose level, with different participants receiving sequential dose-escalation levels to find the Phase 1b recommended dose.
Intervention: Fludarabine (Drug)
Phase 1a: KITE-363 (Dose Escalation)
Participants with relapsing forms of multiple sclerosis (RMS), progressive forms of multiple sclerosis (PMS), myasthenia gravis (MG), and/or chronic inflammatory demyelinating polyneuropathy (CIDP) will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by infusion of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells at a single dose level, with different participants receiving sequential dose-escalation levels to find the Phase 1b recommended dose.
Intervention: Cyclophosphamide (Drug)
Phase 1b: KITE-363 (Dose Expansion)
Participants with RMS, PMS, MG, and/or CIDP 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 RMS, PMS, MG, and/or CIDP will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1a recommended dose of KITE-363 CAR T cells.
Intervention: Fludarabine (Drug)
Phase 1b: KITE-363 (Dose Expansion)
Participants with RMS, PMS, MG, and/or CIDP will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed Phase 1a recommended dose of KITE-363 CAR T cells.
Intervention: Cyclophosphamide (Drug)
Outcomes
Primary Outcomes
Phase 1b: Progressive Forms of MS (PPMS) and (naSPMS): Time to Onset of Confirmed Disability Progression Over 12 Weeks (CDP-12)
Time Frame: Up to 2 years
Phase 1a: Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs)
Time Frame: Up to 2 years
Phase 1a: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363
Time Frame: Up to 28 days
Phase 1b: (All Cohorts) Percentage of Participants Experiencing TEAEs
Time Frame: Up to 2 years
Phase 1b: Relapsing Forms of MS (RRMS) and (aSPMS): Number of New T1 Gadolinium Enhancing (GadE+) Lesions on Magnetic Resonance Imaging (MRI) at Week 12
Time Frame: Week 12
This will be reported in participants with relapsing forms of Multiple Sclerosis MS (RRMS) and (aSPMS).
Phase 1b: Relapsing Forms of MS (RRMS and aSPMS): Number of New and/or Enlarging T2 Lesions on MRI at Week 12
Time Frame: Week 12
Phase 1b: Myasthenia Gravis (MG): Proportion of Participants of MG Activities of Daily Living (MG-ADL) Responders
Time Frame: Up to Week 24
The MG-ADL is a scale to measure the functional impact of MG on daily activities. The total score ranges from 0 to 24, with higher scores indicating greater disability and disease burden.
Phase 1b: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Proportion of Participants with Confirmed Evidence of Clinical Improvement at Week 24
Time Frame: Week 24
Clinical improvement will be analyzed using inflammatory neuropathy cause and treatment (INCAT) scale. The INCAT score is a clinician administered tool used to assess functional disability in participants with CIDP. The total scores range from 0 to 10, higher scores indicating greater disability and lower score would indicate clinical improvement.
Secondary Outcomes
- Relapsing forms of MS (RRMS and aSPMS): Annual Relapse Rate(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Proportion of Participants With CDP-12(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Proportion of Participants With CDP-24(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Time to Onset of CDP-12(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Time to Onset of CDP-24(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Proportion of Participants with No Evidence of Disease Activity (NEDA)(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Expanded Disability Status Scale (EDSS) Score Over Time(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Timed 25-foot Walk (T25FW) Score Over Time(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in 9-hole Peg Test Dominant/Non-dominant (9-HPT D/ND) Score Over Time(Up to 2 years)
- Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Symbol Digit Modalities Test (SDMT) Score Over Time(Up to 2 years)
- Progressive Forms of MS (PPMS and naSPMS): Proportion of Participants with CDP-12(Up to 2 years)
- Progressive Forms of MS (PPMS and naSPMS): Proportion of Participants with CDP-24(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Time to Onset of CDP-24(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Number of new and Enlarging T2 Lesions on MRI(Up to 2 years)
- Relapsing forms of MS (RRMS and aSPMS): Percentage of Participants With NEDA(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Change From Baseline in EDSS Over Time(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Change From Baseline in T25FW Over Time(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Change From Baseline in 9-HPT D/ND Over Time(Up to 2 years)
- Progressive forms of MS (PPMS and naSPMS): Change From Baseline in SDMT Over Time(Up to 2 years)
- MG: Proportion of Participants With at Least a 2-Point or 5 Point Improvement in MG-ADL Score up to Week 24(Up to 24 weeks)
- MG: Change From Baseline in MG-ADL Score at Week 24(Baseline, Week 24)
- MG: Proportion of Participants With Minimal Symptom Expression (MG-ADL Score of 0 or 1 Point)(Up to 2 years)
- MG: Proportion of Participants With at Least a 3-point or 5-point Improvement in Medical Research Council (QMG) Score up to Week 24(Baseline, Week 24)
- MG: Change From Baseline in QMG Score to Week 24(Baseline, Week 24)
- MG: Proportion of Participants With at Least a 3-Point Improvement in MG-C Score up to Week 24(Baseline, Up to 24 weeks)
- Change From Baseline in MG-C Scale Score at Week 24(Baseline, Week 24)
- MG: Number of Participants With Changes in Myasthenia Gravis Foundation of American Post-Intervention Status (MGFA-PIS), Including Minimal Manifestation, Complete Stable Remission, Pharmacologic Remission(Up to 2 years)
- CIDP: Time to First Adjusted INCAT Deterioration(Up to 2 years)
- CIDP: Proportion of Participants With Confirmed Evidence of Clinical Improvement(Week 48)
- CIDP: Proportion of Participants With Evidence of Clinical Improvement(Up to week 48)
- CIDP: Time to Disease Progression by I-RODS(Baseline, Up to 48 Weeks)
- CIDP: Change From Baseline Over Time in 24-Item I-RODS Score(Up to 2 years)
- CIDP: Change From Baseline Over Time in Medical Research Council (MRC) Sum Score(Up to 2 years)
- CIDP: Change From Baseline Over Time in Adjusted INCAT Score(Up to 2 years)
- CIDP: Change From Baseline Over Time in Timed Up and Go (TUG) Score(Up to 2 years)
- CIDP: Change From Baseline Over Time in Mean grip strength assessed by Martin Vigorimeter(Up to 2 years)
- Levels of T-cells in Blood(Up to 2 years)
- Pharmacokinetics: Levels of Chimeric Antigen Receptor (CAR) T-cells in Blood(Up to 2 years)
- Pharmacodynamics Parameters: Levels of B cells in Blood(Up to 2 years)
- Pharmacodynamics Parameters: Levels of Disease-Specific Biomarkers and Autoantibodies in Blood(Up to 2 years)
- Proportion of Participants With of Antibodies Against the KITE-363 CAR T cells in Blood(Up to 2 years)
- Pharmacodynamics Parameters: Levels of Cytokines and Chemokines in Blood(Up to 2 years)