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This is a phase I/II study to assess safety, efficacy, and cellular kinetics of YTB323 in participants with treatment-resistant generalized myasthenia gravis. YTB323 is a Biological CAR-T cell therapy.
This is an open-label, multi-center, non-confirmatory study intended to assess safety, efficacy, and cellular kinetics of YTB323 treatment in participants with treatment-resistant generalized myasthenia gravis in order to enable a benefit to risk assessment for further development in generalized myasthenia gravis (gMG). The study plans to enroll approximately 15 participants with treatment-resistant gMG. The study utilizes a single dose design across 2 cohorts, consisting of a sentinel cohort of 3 patients followed by an expansion cohort of an additional 12 patients.
All participants dosed with YTB323 will be followed until 15 years after YTB323 administration in the Long-Term Follow-up (LTFU).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| YTB323 | Experimental | YTB323 single intravenous (i.v.) infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YTB323 | Genetic | CAR-T cell suspension for intravenous infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Incidence of AE's, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANs), changes in Vital Signs, Laboratory parameters, ECG, and neurological status qualifying and reported as AEs. | Baseline up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Pharmacokinetics (PK) of YTB323 - CMAX | Measured by Cmax - The maximum plasma concentration of YTB323 | Pre-dose Day 1 up to 2 years |
| Plasma Pharmacokinetics (PK) of YTB323 - AUC | Measured by AUC - Area under the curve of YTB323 |
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Inclusion Criteria:
Confirmed gMG diagnosis supported by the following:
MGFA Class III-IVa (gMG) at screening
Treatment-resistant gMG as defined by: MG-ADL score ≥ 6 (≥50% non-ocular) at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy.
If on chronic corticosteroids, must be on a stable dose of corticosteroids for ≥1 month prior to screening and have the ability and willingness to taper to a maximum dose of 10 mg prednisolone daily or equivalent at least one week before leukapheresis
If treated with cholinesterase inhibitors, patients must be on a stable dose for at least two weeks prior to screening
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Novartis Pharmaceuticals | Contact | 1-888-669-6682 | novartis.email@novartis.com | |
| Novartis Pharmaceuticals | Contact | +41613241111 |
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Univ Cali Irvine ALS Neuromuscular | Recruiting | Orange | California | 92868 | United States |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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| Pre-dose Day 1 up to 2 years |
| Plasma Pharmacokinetics (PK) of YTB323 - Tmax | Measured by Tmax - Time to Reach the Maximum Concentration After Drug Administration of YTB323 | Pre-dose Day 1 up to 2 years |
| Plasma Pharmacokinetics (PK) of YTB323 - Clast | Clast is defined as the Last observed (quantifiable) plasma concentration (Clast) | Pre-dose Day 1 up to 2 years |
| Plasma Pharmacokinetics (PK) of YTB323 - Tlast | Tlast is defined as Time of Last Measurable Concentration | Pre-dose Day 1 up to 2 years |
| Cellular immunogenicity of YTB323 | Incidence and prevalence of pre-existing and treatment induced humoral immunogenicity of YTB323 | Pre-dose lymphodepletion up to 2 years |
| Humoral immunogenicity of YTB323 | Incidence and prevalence of pre-existing and treatment induced cellular immunogenicity of YTB323 | Pre-dose lymphodepletion up to 2 years |
| Neutralizing immunogenicity of YTB323 | Incidence and prevalence of pre-existing and treatment induced neutralizing immunogenicity of YTB323 | Pre-dose lymphodepletion up to 2 years |
| Change from Baseline of MG-ADL score | The Myasthenia Gravis Activities of Living (MG-ADL) scale is an 8-item patient-reported scale that measures myasthenia gravis symptoms and functional status, to be administered by physician or trained study evaluator. The MG-ADL is an outcome measure assessing MG symptoms and functional activities related to activities of daily living. Each of the items is scored from 0 (normal) to 3 (most severe), providing a total score ranging from 0 to 24, where higher scores indicate greater severity of symptoms. It is composed of items related to patients' assessment of functional disability secondary to ocular (two items), bulbar (three items), respiratory (one item), and gross motor or limb impairment (two items). | Baseline up to 2 years |
| Change from Baseline of QMG total score | The Quantitative Myasthenia Gravis (QMG) score is a standardized validated quantitative strength scoring system developed specifically for MG. The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. Each item is quantitatively assessed and scored from 0 to 3 (where 3 represents the most severe), providing a total QMG score ranging from 0 to 39 where higher scores indicate greater disease activity. The QMG is composed of the following items: ocular (two items), facial (one item), bulbar (two items), gross motor (six items), axial (one item), and respiratory (one item). | Baseline up to 2 years |
| Proportion of patients with a ≥3-point reduction of QMG total score sustained for 6 months post Baseline | The QMG score is a standardized validated quantitative strength scoring system developed specifically for MG. The QMG is a 13-item direct physician assessment scoring system that quantifies disease severity based on impairments of body functions and structures. Each item is quantitatively assessed and scored from 0 to 3 (where 3 represents the most severe), providing a total QMG score ranging from 0 to 39, where higher scores indicate greater disease severity. The QMG is composed of the following items: ocular (two items), facial (one item), bulbar (two items), gross motor (six items), axial (one item), and respiratory (one item). | Baseline up to 2 years |
| Proportion of patients with a ≥2-point reduction of MG-ADL score sustained for 6 months post Baseline | The Myasthenia Gravis Activities of Living (MG-ADL) scale is an 8-item patient-reported scale that measures myasthenia gravis symptoms and functional status, to be administered by physician or trained study evaluator. The MG-ADL is an outcome measure assessing MG symptoms and functional activities related to activities of daily living. Each of the items is scored from 0 (normal) to 3 (most severe), providing a total score ranging from 0 to 24, where higher scores indicate greater severity of symptoms. It is composed of items related to patients' assessment of functional disability secondary to ocular (two items), bulbar (three items), respiratory (one item), and gross motor or limb impairment (two items). | Baseline up to 2 years |
| Proportion of patients with a MGFA-PIS of minimal manifestations (MM) or better and sustained for 6 months post Baseline | The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) is a physician-assessed determination of the overall clinical state of an MG patient at any time after initiation of treatment for MG. MM or better includes Minimal Manifestation (MM): the patient has no symptoms or functional limitations from MG but has some weakness on examination of some muscles; Complete Stable Remission (CSR): the patient has had no symptoms or signs of MG for at least 1 year and has received no therapy for MG during that time. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted; or Pharmacologic Remission (PR): the same criteria as for CSR except that the patient continues to take some form of therapy for MG. | Baseline up to 2 years |
| Wake Forest Univ School of Medicine | Recruiting | Winston-Salem | North Carolina | 27157-1052 | United States |
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| Thomas Jefferson University | Recruiting | Philadelphia | Pennsylvania | 19107 | United States |
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| Houston Methodist Hospital | Recruiting | Houston | Texas | 77030 | United States |
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| Novartis Investigative Site | Recruiting | Bordeaux | 33076 | France |
| Novartis Investigative Site | Recruiting | Brest | 29200 | France |
| Novartis Investigative Site | Recruiting | Lille | 59037 | France |
| Novartis Investigative Site | Recruiting | Chiba | Chiba | 2608677 | Japan |
| Novartis Investigative Site | Recruiting | Kyoto | 6068507 | Japan |
| Novartis Investigative Site | Recruiting | Sheffield | South Yorkshire | S10 2JF | United Kingdom |
| Novartis Investigative Site | Recruiting | London | SE5 9RS | United Kingdom |
| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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