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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06675864




Registration number
NCT06675864
Ethics application status
Date submitted
4/11/2024
Date registered
5/11/2024

Titles & IDs
Public title
Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS)
Scientific title
An Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression, and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS)
Secondary ID [1] 0 0
CYTB323r12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressive Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - rapcabtagene autoleucel (YTB323)

Experimental: YTB323 Cohort 1 - Participants will receive one dose of YTB323

Experimental: YTB323 Cohort 2 - Participants will receive one dose of YTB323

Experimental: YTB323 Cohort 3 - Participants will receive one dose of YTB323

Experimental: YTB323 Cohort 4 - Participants will receive one dose of YTB323


Treatment: Other: rapcabtagene autoleucel (YTB323)
CAR-T cell suspension for intravenous infusion
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Day 1 through Year 2
Secondary outcome [1] 0 0
Measure of Disability: Expanded Disability Status Scale (EDSS).
Timepoint [1] 0 0
Day 1 through Year 2
Secondary outcome [2] 0 0
Measure of Disability: Short Form Health Survey (SF-36 v2)
Timepoint [2] 0 0
Day 1 through Year 2
Secondary outcome [3] 0 0
Measure of Disability: Timed 25 Foot Walk (T25FW)
Timepoint [3] 0 0
Day 1 through Year 2
Secondary outcome [4] 0 0
Measure of Disability: 9 Hole Peg Test (9HPT)
Timepoint [4] 0 0
Day 1 through Year 2
Secondary outcome [5] 0 0
Measure of Disability: Symbol Digit Modalities Test (SDMT)
Timepoint [5] 0 0
Day 1 through Year 2
Secondary outcome [6] 0 0
Modified Fatigue Impact Scale (MFIS)
Timepoint [6] 0 0
Day 1 through Year 2
Secondary outcome [7] 0 0
Plasma Pharmacokinetics (PK) of YTB323 - CMAX
Timepoint [7] 0 0
Day 1 through Year 2
Secondary outcome [8] 0 0
Plasma Pharmacokinetics (PK) of YTB323 - AUC
Timepoint [8] 0 0
Day 1 Through Year 2
Secondary outcome [9] 0 0
Plasma Pharmacokinetics (PK) of YTB323 - Tmax
Timepoint [9] 0 0
Day 1 Through Year 2
Secondary outcome [10] 0 0
Plasma Pharmacokinetics (PK) of YTB323 - Clast
Timepoint [10] 0 0
Day 1 Through Year 2
Secondary outcome [11] 0 0
Plasma Pharmacokinetics (PK) of YTB323 - Tlast
Timepoint [11] 0 0
Day 1 through Year 2
Secondary outcome [12] 0 0
Humoral Immunogenicity of YTB323
Timepoint [12] 0 0
Day 1 through Year 2
Secondary outcome [13] 0 0
Cellular Immunogenicity of YTB323
Timepoint [13] 0 0
Day 1 through Year 2
Secondary outcome [14] 0 0
Manufacture success (defined as meeting release specifications and at or above the target dose)
Timepoint [14] 0 0
Day -9 to Day -2

Eligibility
Key inclusion criteria
Key

1. Male or female participants 18 to 60 years (inclusive) at screening.
2. Signed informed consent must be obtained prior to participation in the study.
3. Able to communicate well with the investigator, to understand and comply with the requirements of the study including:

* Able to undergo lumbar puncture (LP), blood draws, tolerate brain MRI, and able to participate and tolerate all study procedures at study visits.
4. Diagnosis of SPMS or PPMS according to the 2017 McDonald diagnostic criteria (Thompson et al 2018) as confirmed at screening visit.
5. Disease duration less than 15 years.
6. Ambulatory Patients (EDSS3 to 6.5 inclusive) at screening.
7. Evidence of recent (within 1 year) disease progression of =0.5 on the EDSS scale.
8. No relapse in the last year at screening.
9. No Gd-enhancing lesion on brain MRI at screening.

Key
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosis of relapsing multiple sclerosis (RMS) or active PMS according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018) at screening.
2. History of, or current, clinically significant CNS disease except MS (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy, history of seizures or epilepsy) or neurological disorders which may mimic MS at screening.
3. Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to screening).
4. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML prior to screening.
5. 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.
6. Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations.
7. Any prior stem cell therapy or organ transplantation or gene therapy.
8. Any contraindications to LP, including but not limited to:

* Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance of the LP, or increase the risk of the procedure for the participant.
* Presence of risk for increased or uncontrolled bleeding (including but not limited to vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count).
* Participants on anticoagulants (e.g., warfarin) or antiplatelets [except for low-dose aspirin (100 mg/day or lower) and low-dose nonsteroidal anti-inflammatory drugs such as ibuprofen (600 mg/day or lower) which are allowed], are not eligible to participate.
9. Not willing or able to have MRI scans as per protocol e.g. due to claustrophobia, or absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator).
10. Pregnant or nursing (lactating) women.
11. Past surgical history of splenectomy.
12. Evidence of active or latent tuberculosis (TB) infection by QuantiFERON® TB-Gold assay (or equivalent) performed at Screening by central lab. In case of unclear or indeterminate test results, the Investigator should consult with an infectious disease expert to exclude the diagnosis of active or latent TB infection and document this in the source data. Participant should be excluded if they have any signs of active TB observed in available lung imaging (e.g., X-ray or HRCT).
13. Any psychiatric, pulmonary (including, history of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephrotic syndrome), hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant, prior to screening.
14. Grade 2 or higher thromboembolic event in the past 4 weeks prior to or during Screening or evidence of disorders of coagulation or platelet function including subjects that require chronic use of anticoagulation or antiplatelet drugs (please refer to the key exclusion criteria no. 8 for the exceptions).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/12/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
13/06/2030
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Quebec
Country [2] 0 0
Switzerland
State/province [2] 0 0
Bern

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
+41613241111
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06675864