Clinical trial • Phase II • Immunology|Neurology
KYV-101 (Anti-CD19 CAR T cells) for Primary progressive multiple sclerosis|Secondary progressive multiple sclerosis
Phase II trial of KYV-101 (Anti-CD19 CAR T cells) for Primary progressive multiple sclerosis|Secondary progressive multiple sclerosis.
Overview
- Trial Therapeutic Area
- Immunology|Neurology
- Trial Disease
- Primary progressive multiple sclerosis|Secondary progressive multiple sclerosis
- Trial Stage
- Phase II
- Drug Modality
- Cell therapy|Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 24-05-2024
- First CTIS Authorization Date
- 01-10-2024
Trial design
Randomised, open-label, continuing anti-cd20 monoclonal antibody (control arm). comparator agents listed in part i/part ii product groups include: kesimpta (ofatumumab) 20 mg solution for injection (subcutaneous); ocrevus (ocrelizumab) 300 mg concentrate for infusion (intravenous); mabthera (rituximab) 100 mg / 500 mg concentrate for infusion (intravenous); briumvi (ublituximab) 150 mg concentrate for infusion (intravenous). specific schedules not detailed in the provided record. Phase II trial in Belgium, Austria, Italy and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Continuing anti-CD20 monoclonal antibody (control arm). Comparator agents listed in Part I/Part II product groups include: Kesimpta (ofatumumab) 20 mg solution for injection (subcutaneous); Ocrevus (ocrelizumab) 300 mg concentrate for infusion (intravenous); MabThera (rituximab) 100 mg / 500 mg concentrate for infusion (intravenous); Briumvi (ublituximab) 150 mg concentrate for infusion (intravenous). Specific schedules not detailed in the provided record.
- Target Sample Size
- 88
Eligibility
Recruits 88 Vulnerable population selected; no further details on consent or assent handling provided..
- Vulnerable Population
- Vulnerable population selected; no further details on consent or assent handling provided.
Inclusion criteria
- {"criterion_text":"- Subject must be 18 to 60 years of age (inclusive)."}
- {"criterion_text":"- Subject must have a history of diagnosis of PPMS or SPMS"}
- {"criterion_text":"- History of treatment with anti-CD20 mAb with continuing evidence of worsening physical disability over a period of ≥6 months with documented evidence of clinical disability progression within the 2 years prior to inclusion. Patients with active SPMS should also have shown inadequate response or intolerance to another DMT (e.g., sphingosine-1-phosphate (S1P) receptor modulator), subject to availability."}
Exclusion criteria
- {"criterion_text":"- Monophasic disease, radiologically isolated syndrome, clinically isolated syndrome, progressive solitary sclerosis or relapsing-remitting disease as defined by the 2017 McDonald criteria (Thompson 2018)."}
- {"criterion_text":"- History of neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD)."}
Endpoints
Primary endpoints
- {"endpoint_text":"- 1. Confirmed disability progression, defined as an increase in the EDSS","definition_or_measurement_approach":"Defined as an increase in the EDSS (Expanded Disability Status Scale)."}
Secondary endpoints
- {"endpoint_text":"- 2a. Incidence and severity of AEs, AESIs, and SAEs","definition_or_measurement_approach":"Incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)."}
- {"endpoint_text":"- 2b1. Composite Confirmed Disability Progression (CCPD) defined as disability progression measured by EDSS","definition_or_measurement_approach":"Composite Confirmed Disability Progression (CCPD), defined as disability progression measured by EDSS."}
- {"endpoint_text":"- 2b2. Impact on clinical disability as defined by the number of days from randomization to the primary outcome.","definition_or_measurement_approach":"Impact measured as number of days from randomization to the primary outcome."}
- {"endpoint_text":"- 2b3. Disability as measured by EDSS change from pretreatment baseline to end of study.","definition_or_measurement_approach":"Measured as EDSS change from pretreatment baseline to end of study."}
- {"endpoint_text":"- 2b4. Annualized relapse rate (ARR) in patients with active SPMS (relapse in the past 2 years or active lesions on MRI)","definition_or_measurement_approach":"Annualized relapse rate (ARR) in patients with active SPMS as defined by relapse history or active MRI lesions."}
- {"endpoint_text":"- 2b5. Comparison of end-of-study brain MRI compared to baseline scan in T2 burden of demyelinating disease, baseline to end of study, including whole brain volume and grey matter volume changes from treatment baseline to end of study.","definition_or_measurement_approach":"MRI-based comparison of T2 lesion burden and volumetric measures (whole brain and grey matter volume) from baseline to end of study."}
- {"endpoint_text":"- 2b6. For the CSF consenting subset, comparison of interval changes in unmatched intrathecal oligoclonal bands treatment from baseline to end of study.","definition_or_measurement_approach":"For CSF consent subset, comparison of changes in intrathecal oligoclonal bands from baseline to end of study."}
- {"endpoint_text":"- 2c. CAR-positive T-cell counts, CAR transgene level, B-cell counts over time, systemic cytokine concentrations.","definition_or_measurement_approach":"Laboratory measurements over time including CAR-positive T-cell counts, CAR transgene level, B-cell counts, and systemic cytokine concentrations."}
- {"endpoint_text":"- 2d. Presence of anti-KYV-101 antibodies.","definition_or_measurement_approach":"Assessment of presence of anti-KYV-101 antibodies (immunogenicity)."}
Recruitment
- Planned Sample Size
- 88
- Recruitment Window Months
- 44
- Consent Approach
- Informed consent to be provided by adult subjects (aged 18–60). No paediatric assent or age-specific consent documents are described in the provided record; languages for consent documents are not specified.
Geography
- Total Number Of Sites
- 10
- Total Number Of Participants
- 88
Belgium
- Earliest CTIS Part Ii Submission Date
- 19-08-2024
- Latest Decision Or Authorization Date
- 02-10-2024
- Processing Time Days
- 44
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Antwerp University Hospital
- Department Name
- Neurology
- Contact Person Name
- Barbara Willekens
- Contact Person Email
- barbara.willekens@uza.be
Austria
- Earliest CTIS Part Ii Submission Date
- 05-09-2024
- Latest Decision Or Authorization Date
- 07-10-2024
- Processing Time Days
- 32
- Number Of Sites
- 1
- Number Of Participants
- 10
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- University Clinic for Transfusion Medicine and Cell Therapy
- Contact Person Name
- Antonia Maria Susanne Müller
- Contact Person Email
- antonia.mueller@meduniwien.ac.at
Italy
- Earliest CTIS Part Ii Submission Date
- 05-09-2024
- Latest Decision Or Authorization Date
- 02-10-2024
- Processing Time Days
- 27
- Number Of Sites
- 1
- Number Of Participants
- 5
Sites
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Neurology Unit
- Contact Person Name
- Massimo Filippi
- Contact Person Email
- filippi.massimo@hsr.it
Germany
- Earliest CTIS Part Ii Submission Date
- 13-06-2024
- Latest Decision Or Authorization Date
- 01-10-2024
- Processing Time Days
- 110
- Number Of Sites
- 7
- Number Of Participants
- 70
Sites
- Site Name
- Universitaetsklinikum Jena KöR
- Department Name
- Klinik für Neurologie
- Contact Person Name
- Christian Geis
- Contact Person Email
- Christian.Geis@med.unijena.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Zentrum für Onkologie Interdisziplinäre Klinik und Poliklinik für Stammzelltransplantation
- Contact Person Name
- Francis Ayuketang Ayuk
- Contact Person Email
- ayuketang@uke.de
- Site Name
- Katholisches Klinikum Bochum gGmbH
- Department Name
- Neurologische Universitätsklinik
- Contact Person Name
- Jeremias Motte
- Contact Person Email
- jeremias.motte@ruhr-unibochum.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- 3. Medizinische Klinik
- Contact Person Name
- Judith Hecker
- Contact Person Email
- judith.hecker@mri.tum.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Department of Neurology
- Contact Person Name
- Paul Friedemann
- Contact Person Email
- friedemann.paul@charite.de
- Site Name
- Medizinische Hochschule Hannover
- Department Name
- Klinik für Neurologie mit Klinischer Neurophysiologie
- Contact Person Name
- Susanne Petri
- Contact Person Email
- petri.susanne@mhhannover.de
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universitaet Dresden AöR
- Department Name
- Klinik und Poliklinik für Neurologie
- Contact Person Name
- Tjalf Ziemssen
- Contact Person Email
- tjalf.ziemssen@uniklinikumdresden.de
Sponsor
Primary sponsor
- Full Name
- Kyverna Therapeutics Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Pra International
- Responsibilities
- code 4
- Name
- Icon (Lr) Limited
- Responsibilities
- code 4
- Name
- PPD Development LP
- Responsibilities
- codes: 1,10,11,12,13,2,3,5,6,7,8,9
- Name
- Pharmaceutical Research Associates Group B.V.
- Responsibilities
- code 4
Third parties
- {"country":"United States","full_name":"Pra International","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"Imaging","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Precision For Medicine Inc. (Houston)","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Subject Travel and Subject Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"code 4","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Molecularmd Corp.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"codes: 1,10,11,12,13,2,3,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 6,7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Precision For Medicine Inc. (Frederick)","duties_or_roles":"code 5","organisation_type":"Pharmaceutical company"}
- {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Wuxi Advanced Therapies Inc.","duties_or_roles":"Manufacturing","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- KYV-101
- Active Substance
- KYV-101 (Anti-CD19 CAR T cells)
- Modality
- Cell therapy
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Investigational / prodAuthStatus 1
- Maximum Dose
- 33000000 DF dosage form (maxTotalDoseAmount 100000000 DF dosage form)
- Investigational Product Name
- Kesimpta (ofatumumab)
- Active Substance
- Ofatumumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Subcutaneous
- Route
- Subcutaneous
- Authorisation Status
- Marketing authorisation present (prodAuthStatus 2)
- Maximum Dose
- 20 mg (maxTotalDoseAmount 480 mg)
- Investigational Product Name
- Ocrevus (ocrelizumab)
- Active Substance
- Ocrelizumab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Marketing authorisation present (prodAuthStatus 2)
- Maximum Dose
- 600 mg (maxDailyDoseAmount 600 mg; maxTotalAmount 3 g)
- Investigational Product Name
- MabThera (rituximab)
- Active Substance
- Rituximab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Marketing authorisation present (prodAuthStatus 2)
- Maximum Dose
- 1 g (maxDailyDoseAmount 1 g; maxTotalAmount 5 g)
- Investigational Product Name
- Briumvi (ublituximab)
- Active Substance
- Ublituximab
- Modality
- Monoclonal antibody
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- Marketing authorisation present (prodAuthStatus 2)
- Maximum Dose
- 450 mg (maxDailyDoseAmount 450 mg; maxTotalAmount 2.25 g)
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