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 preliminary efficacy of KITE-363 in participants with autoimmune neurologic diseases.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Key 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
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
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 2 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 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 — 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 (naSPMS): Time to Onset of Confirmed Disability Progression Over 12 Weeks (CDP-12) — Up to 2 years
Phase 1b: Myasthenia Gravis (MG): Proportion of Participants of MG Activities of Daily Living (MG-ADL) Responders — 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 — 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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.