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

Gilead Sciences

Status and phase: Not yet enrolling; Phase 1

Conditions: Myasthenia Gravis; Chronic Inflammatory Demyelinating Polyneuropathy; Multiple Sclerosis

Treatments: Drug: Fludarabine; Biological: KITE-363; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT07304154

KT-US-728-0204

Details and patient eligibility

About

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.

Enrollment: 52 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

52 participants in 2 patient groups

Phase 1a: KITE-363 (Dose Escalation)

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Biological: KITE-363

Drug: Fludarabine

Phase 1b: KITE-363 (Dose Expansion)

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Biological: KITE-363

Drug: Fludarabine