Generalized Myasthenia GravisPhase 1/2NCT06704269
Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Generalized Myasthenia Gravis
A Phase 1/2 study testing YTB323 in people with Generalized Myasthenia Gravis, run by Novartis Pharmaceuticals at 11 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Generalized Myasthenia Gravis
- What is being tested?
- YTB323
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 22 Apr 2025to 26 Oct 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed gMG diagnosis supported by the following:
- Documented report of positive serology testing for either AChR antibodies or MuSK antibodies at screening AND at least one of the following:
- History of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography
- History of positive acetylcholinesterase inhibitor test
- Improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician
- MGFA Class III-IVa (gMG) at screening
Show all 9Show fewer
- 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
Who cannot join
- Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V at screening
- History of bone marrow/hematopoietic stem cell or solid organ transplantation.
- Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis
- Other uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, at screening
- Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody, at screening
- Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy).
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States4 sites
Houston Methodist Hospital
Houston, Texas, 77030
Univ Cali Irvine ALS Neuromuscular
Orange, California, 92868
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Wake Forest Univ School of Medicine
Winston-Salem, North Carolina, 27157-1052
France3 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Brest, 29200
Novartis Investigative Site
Lille, 59037
Japan2 sites
Novartis Investigative Site
Chiba, Chiba, 2608677
Novartis Investigative Site
Kyoto, 6068507
United Kingdom2 sites
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
Sheffield, South Yorkshire, S10 2JF
About this study
Official title: An Open-label, Multi-center, Phase I/II Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Treatment-resistant Generalized Myasthenia Gravis
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.
Read the detailed description
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).
- Conditions
- Generalized Myasthenia Gravis
- Being tested
- YTB323
- Keywords
- myasthenia gravis, generalized myasthenia gravis, YTB323, CAR-T
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YTB323Genetic
CAR-T cell suspension for intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| YTB323 | Experimental | YTB323 single intravenous (i.v.) infusion Receives: Genetic: YTB323 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to 2 years
Secondary outcomes (13)
Plasma Pharmacokinetics (PK) of YTB323 - CMAX
Measured by Cmax - The maximum plasma concentration of YTB323
Measured: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - AUC
Measured by AUC - Area under the curve of YTB323
Measured: 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
Measured: 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)
Measured: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - Tlast
Tlast is defined as Time of Last Measurable Concentration
Measured: 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
Measured: Pre-dose lymphodepletion up to 2 years
Humoral immunogenicity of YTB323
Incidence and prevalence of pre-existing and treatment induced cellular immunogenicity of YTB323
Measured: Pre-dose lymphodepletion up to 2 years
Neutralizing immunogenicity of YTB323
Incidence and prevalence of pre-existing and treatment induced neutralizing immunogenicity of YTB323
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: Baseline up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study start22 Apr 2025
- Primary completion26 Oct 2029 (estimated)
- Study completion26 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalized Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06704269
- Sponsor's protocol ID
- CYTB323O12101
- Status last verified
- Aug 2026
- First submitted
- 22 Nov 2024
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center, Phase I/II Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Treatment-resistant Generalized Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT06704269
- Acronym / sponsor ID
- CYTB323O12101
- Conditions
- Generalized Myasthenia Gravis
- Keywords
- myasthenia gravis, generalized myasthenia gravis, YTB323, CAR-T
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 Apr 2025 (actual)
- Primary completion
- 26 Oct 2029 (estimated)
- Study completion
- 26 Oct 2029 (estimated)
- First posted
- 26 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| YTB323 | Experimental | Genetic: YTB323YTB323 single intravenous (i.v.) infusion |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V at screening
- History of bone marrow/hematopoietic stem cell or solid organ transplantation.
- Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C) confirmed by clinical evidence, imaging, or positive laboratory tests one month prior to leukapheresis
- Other uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, at screening
- Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody, at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YTB323CAR-T cell suspension for intravenous infusion | Genetic | YTB323 |
Primary outcome
Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to 2 years
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.
13 secondary outcomes
Plasma Pharmacokinetics (PK) of YTB323 - CMAX
Time frame: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - AUC
Time frame: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - Tmax
Time frame: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - Clast
Time frame: Pre-dose Day 1 up to 2 years
Plasma Pharmacokinetics (PK) of YTB323 - Tlast
Time frame: Pre-dose Day 1 up to 2 years
Cellular immunogenicity of YTB323
Time frame: Pre-dose lymphodepletion up to 2 years
Humoral immunogenicity of YTB323
Time frame: Pre-dose lymphodepletion up to 2 years
Neutralizing immunogenicity of YTB323
Time frame: Pre-dose lymphodepletion up to 2 years
Change from Baseline of MG-ADL score
Time frame: Baseline up to 2 years
Change from Baseline of QMG total score
Time frame: Baseline up to 2 years
Proportion of patients with a ≥3-point reduction of QMG total score sustained for 6 months post Baseline
Time frame: Baseline up to 2 years
Proportion of patients with a ≥2-point reduction of MG-ADL score sustained for 6 months post Baseline
Time frame: 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
Time frame: Baseline up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: Yes. 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
Related trials for Generalized Myasthenia Gravis
Active, not recruitingPhase 3
An Extension Study Evaluating 6-week Treatment Cycles of Rozanolixizumab in Pediatric Study Participants With Generalized Myasthenia Gravis
Generalized Myasthenia Gravis
Recruiting
Holistic Assessment and Remote Digital MONitoring of mYasthenia Gravis Via MyoSense 360
Myasthenia Gravis, Generalized
RecruitingPhase 3
A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis
Myasthenia Gravis
RecruitingPhase 2/3
A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis
Generalized Myasthenia Gravis
Not yet recruitingEarly Phase 1
A Clinical Study to Evaluate the Safety and Efficacy of GT802 Injection in the Treatment of Refractory Generalized Myasthenia Gravis
Generalized Myasthenia Gravis (gMG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing YTB323 in people with Generalized Myasthenia Gravis, run by Novartis Pharmaceuticals at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, France, Japan, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence, severity, and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.