An open-label study to assess safety, efficacy, and cellular kinetics of YTB323 in treatment-resistant generalized myasthenia gravis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

29 Jul 2025 → ongoing

Decision date (initial)

2025-03-05

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic

To assess the safety of YTB323 in patients with treatment-resistant generalized myasthenia gravis (gMG) with antibodies against AChR or MuSK.

Secondary objectives 3

1. To characterize the in vivo cellular kinetics (pharmacokinetics, PK) of YTB323 in peripheral blood by quantitative polymerase chain reaction (qPCR)
2. To characterize the incidence and prevalence of pre-existing and treatment induced immunogenicity (cellular and humoral) of YTB323
3. To assess the effect of YTB323 on gMG disease severity

Conditions and MedDRA coding

Treatment-resistant generalized Myasthenia Gravis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
2. Male or female participants 18-65 years of age with adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)
3. Confirmed gMG diagnosis with documented positive AChR antibodies or MuSK antibodies at screening AND has one of the following: history of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography OR history of positive acetylcholinesterase test OR improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician
4. Generalized myasthenia gravis classified as MGFA Class III-IVa at screening
5. Treatment-resistant gMG as defined by: MG-ADL score ≥6 at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy. Specifically, they must have failed treatment with at least one oral immunomodulatory or steroid-sparing drug (e.g., azathioprine, mycophenolate mofetil, tacrolimus) AND EITHER one approved anti-C5 complement antibody (e.g., eculizumab, ravulizumab) OR an approved FcRn antagonist OR rituximab, OR required two or more rescue therapies (plasma exchange/immunoadsorption or IVIg) for myasthenic worsening/crisis in the 12 months before screening
6. If on chronic corticosteroids, ability and willingness to taper to a maximum dose at least one week before leukapheresis

Exclusion criteria 6

1. Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V (at time of screening)
2. Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C, HIV or TB)
3. History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer or non-invasive malignant polyps that have been removed), treated or untreated, within the past 5 years
4. Known thymic neoplasm or history of thymectomy within 12 months prior to screening
5. Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy)
6. Hypersensitivity and/or contraindications to any product (including its ingredients) to be given to the participant as per the study protocol (e.g., YTB323, tocilizumab, lymphodepleting agents, etc.) or any condition that, in the Investigator's opinion, precludes lymphodepleting chemotherapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence, severity, and frequency of Adverse Events (AEs) (including CRS and ICANs) and change from baseline in safety parameters including, but not limited to: Vital signs, laboratory parameters, ECG, and neurological status

Secondary endpoints 3

1. YTB323 transgene levels by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)
2. Pre-existing and treatment induced immunogenicity (cellular, humoral, neutralizing antibodies) of YTB323
3. At various timepoints: • Change from BL of MG-ADL score • Change from BL of QMG total score • Whether or not patient achieves a ≥3-point reduction of QMG total score sustained for 6 months post BL • Whether or not patient achieves a ≥2-point reduction of MG-ADL score sustained for 6 months post BL • Whether or not a patient achieves MGFA Post intervention Status (PIS) of minimal manifestations (MM) or better and sustained for 6 months post BL

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 12

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications