Recruiting
Phase 1
Study of KITE-363 in Participants With Autoimmune Neurologic Diseases That Did Not Respond to Usual Treatment
Condition(s) studied
Chronic Inflammatory Demyelinating PolyneuropathyMyasthenia GravisMultiple Sclerosis
Investigational drug(s) / intervention(s)
KITE-363: A single infusion of CAR-transduced autologous T cells administered as intravenous infusion.
Fludarabine: Administered intravenously
Cyclophosphamide: Administered intravenously
Study 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 safety and preliminary efficacy of KITE-363 in participants with autoimmune neurologic diseases
Eligibility
Key Inclusion Criteria:
* Age 18 through 65 for relapsing forms of MS, 18 through 75 for progressive forms of MS, above 18 years of age for MG and CIDP.
* Reproductive status-related eligibility and contraception requirements:
* Individuals 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 6.0
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-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. Individuals with confirmed IgG4 paranodal antibodies (eg, NF155, CNTN1, Caspr1) are eligible if they meet EFNS/PNS 2010 criteria
* For the Phase 1b CIDP cohort, diagnosis will be confirmed by independent adjudication once the adjudication committee is established and operational
* CIDP Disease Activity Status (CDAS) score ≥ 3 at screening and confirmed at the final pre treatment assessment prior to infusion
* Inflammatory neuropathy cause and treatment (INCAT) score ≥ 3 at screening and confirmed at one of more protocol-defined baseline assessments during the Extended Screening Period with Observational Run-in; individuals must also continue to meet clinical eligibility criteria at the final pre-treatment assessment prior to infusion
* Inadequate response to previous therapies despite adequate trial of standard of care therapy (≥ 8-12 weeks at standard dosing with stable regimen of either steroids, IVIg, SCIg, plasmapheresis exchange (PLEX), rituximab or anti-FcRN) and either failure, intolerance, or contraindication to at least one additional standard therapy (ie, steroids, IVIg, subcutaneous immunoglobulin (SCIg), plasmapheresis exchange (PLEX), rituximab, or anti FcRN), unless medically inappropriate OR Unable to tolerate standard of care resulting in discontinuation 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
Key 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
* History of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
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.
Primary outcome measure(s)
- Phase 1a: Percentage of Participants Experiencing Treatment-emergent Adverse Event (TEAEs) — Up to 3 years
- Phase 1a: Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 — Up to 28 days
- Phase 1b: (All Cohorts) Percentage of Participants Experiencing TEAEs — Up to 3 years
- Phase 1b: Relapsing Forms of MS (RRMS) and Active Secondary-progressive Multiple Sclerosis (aSPMS): Number of New T1 Gadolinium Enhancing (GadE+) Lesions on Magnetic Resonance Imaging (MRI) at Week 12 — 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 — Week 12
- Phase 1b: Progressive Forms of MS (PPMS) and Non-active Secondary-progressive Multiple Sclerosis (naSPMS): Time to Onset of Confirmed Disability Progression Over 12 Weeks (CDP-12) — Up to 3 years
- Phase 1b: Myasthenia Gravis (MG): Proportion of Participants of MG Activities of Daily Living (MG-ADL) Responders — Up to 3 years
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: CIDP: Proportion of Participants with a ≥ 2 Points Improvement from Baseline in aINCAT Score at Week 24, in the Absence of CIDP Rescue Therapy or Initiation of New Maintenance Immunomodulatory Therapy — Up to 3 years
Clinical improvement will be analyzed using adjusted inflammatory neuropathy cause and treatment (aINCAT) scale. The INCAT score is a clinician administered tool used to assess functional disability in participants with chronic inflammatory demyelinating polyneuropathy (CIDP). The total scores range from 0 to 10, higher scores indicating greater disability and lower score would indicate clinical improvement.
Trial sites (10)
| Facility | City | Region | Status |
| Hoag Memorial Hospital Presbyterian |
Newport Beach |
California |
Recruiting |
| Stanford Neuroscience Health Center |
Palo Alto |
California |
Recruiting |
| Columbia University Irving Medical Center |
New York |
New York |
Recruiting |
| LDS Hospital - Intermountain Health |
Salt Lake City |
Utah |
Recruiting |
| Fred Hutchinson Cancer Center |
Seattle |
Washington |
Recruiting |
| Concord Repatriation General Hospital |
Sydney |
New South Wales |
Recruiting |
| Corner Hawkesbury Road and Darcy Road |
Westmead |
New South Wales |
Recruiting |
| Centre Intégré Universitaire de Sante et Services Sociaux de L'Est de I'lle de Montreal / installation Hopital Maisonneuve-Rosemont |
Montreal |
Canada |
Recruiting |
| Jewish General Hospital |
Montreal |
Canada |
Recruiting |
| The Ottawa Hospital - General Campus |
Ottawa |
Canada |
Recruiting |
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