A Study Evaluating the Safety and Efficacy of KITE-363 in Relapsed/Refractory Autoimmune Neurologic 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 Relapsed/Refractory Autoimmune Neurologic Diseases

Overview

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.

Interventions

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

Primary outcome measures

• 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]
• 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: 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 1b: Myasthenia Gravis (MG): Proportion of Participants of MG Activities of Daily Living (MG-ADL) Responders [Time frame: Up to Week 24]
• Phase 1b: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): Proportion of Participants with Confirmed Evidence of Clinical Improvement at Week 24 [Time frame: Week 24]

Secondary outcome measures (12)

• Relapsing forms of MS (RRMS and aSPMS): Annual Relapse Rate [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Proportion of Participants With CDP-12 [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Proportion of Participants With CDP-24 [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Time to Onset of CDP-12 [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Time to Onset of CDP-24 [Time frame: Up to 2 years]
• Progressive forms of MS (PPMS and naSPMS): Proportion of Participants with No Evidence of Disease Activity (NEDA) [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Expanded Disability Status Scale (EDSS) Score Over Time [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Timed 25-foot Walk (T25FW) Score Over Time [Time frame: 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 [Time frame: Up to 2 years]
• Relapsing Forms of MS (RRMS and aSPMS): Change From Baseline in Symbol Digit Modalities Test (SDMT) Score Over Time [Time frame: Up to 2 years]
• Progressive Forms of MS (PPMS and naSPMS): Proportion of Participants with CDP-12 [Time frame: Up to 2 years]
• Progressive Forms of MS (PPMS and naSPMS): Proportion of Participants with CDP-24 [Time frame: Up to 2 years]

Eligibility criteria

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
• Absence of clinical relapses for at least 24 months
• No evidence of Gadolinium enhancing (GadE+) on magnetic resonance imaging (MRI) brain at screening or baseline
• EDSS of 3 to 6.5 who are ambulatory

Inclusion Criteria for myasthenia gravis (MG):

• Documentation of autoantibodies against acetylcholine receptor (AChR), muscle-specific kinase (MuSK), or low-density lipoprotein receptor-related protein 4 (LRP4)
• Diagnosis of MG with generalized weakness meeting criteria as defined by the Myasthenia Gravis Foundation of American (MGFA) classification of II- IV at screening
• Myasthenia Gravis Activities of Daily Living (MG-ADL) score ≥ 6 (> 50% of the total score due to non-ocular symptoms)
• Quantitative Myasthenia Gravis (QMG) score ≥ 10
• Inadequate response to previous therapies while taking at least 2 classes of immunosuppressants (ie, steroids, azathioprine (AZA), mycophenolate mofetil (MMF), intravenous immunoglobulin (IVIg), biologics (eg, rituximab, anti-neonatal fragment crystallizable (Fc) receptor (FcRN) class, and anti-complement class))
• Thymectomy allowed if completed ≥ 12 months prior to screening

Inclusion Criteria for chronic inflammatory demyelinating polyneuropathy (CIDP):

• Probable or definite CIDP as defined by the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria, relapsing or progressive forms
• CIDP Disease Activity Status (CDAS) score ≥ 3 at screening
• Inflammatory neuropathy cause and treatment (INCAT) score ≥ 3
• Inadequate response to previous therapies despite standard of care therapy (ie, steroids, IVIg, subcutaneous immunoglobulin (SCIg), plasmapheresis exchange (PLEX), rituximab, or anti FcRN) OR Unable to tolerate standard of care due to side effects with ongoing disease activity
• Except for nodal/paranodal CIDP, historical documentation of objective improvement in the past 24 months while on IVIg, SCIg, PLEX, or anti-FcRN OR Historical documentation of objective disease worsening in the past 24 months when IVIg, SCIg, PLEX, or anti-FcRN has been reduced or interrupted

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

Exclusion Criteria for CIDP:

• Pure sensory CIDP and focal CIDP
• Polyneuropathy of other causes

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

• Stanford Neuroscience Health Center — Palo Alto
• Columbia University Irving Medical Center — New York
• LDS Hospital - Intermountain Health — Salt Lake City
• Fred Hutchinson Cancer Center — Seattle

Australia · 2 centers

• Concord Repatriation General Hospital — Sydney
• Corner Hawkesbury Road and Darcy Road — Westmead

Identifiers

NCT: NCT07304154 · KT-US-728-0204

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗