Clinical trial NCT06220201: A Study to Evaluate the Safety, Tolerability, Efficacy, and Drug Levels of CC-97540 in Participants With Relapsing Forms of Multiple Sclerosis, Progressive Forms of Multiple Sclerosis or Refractory Myasthenia Gravis (MG) (Breakfree-2)
Official title: A Phase 1, Multicenter, Single-arm, Dose-escalation Study of CC-97540 (BMS-986353), CD19-Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, Evaluating Safety and Tolerability in Participants With Autoimmune Neurological Diseases: Relapsing Forms of Multiple Sclerosis (RMS), Progressive Forms of Multiple Sclerosis (PMS), or Refractory Myasthenia Gravis (MG).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis
Myasthenia Gravis
Keywords: CC-97540
CAR T
CART
NEX T
NEXT
BMS-986353
RMS
PMS
Multiple sclerosis
RRMS
aSPMS
PPMS
iSPMS
MG
gMG
refractory myasthenia gravis
general myasthenia gravis
CD19
Lead sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2024-01-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, efficacy, and drug levels of CC-97540 in participants with Relapsing Forms of Multiple Sclerosis (RMS), Progressive Forms of Multiple Sclerosis (PMS) or Refractory Myasthenia Gravis (MG).


Eligibility criteria: Inclusion Criteria

- Relapsing forms of Multiple Sclerosis (RMS) - Cohort 1.

i) Participants must have an Expanded Disability Status Scale (EDSS) of ≥ 3.0 and ≤ 5.5.

ii) Participants must have a diagnosis of Multiple Sclerosis (MS) with relapsed/refractory MS or conversion to active secondary progressive multiple sclerosis (aSPMS), and worsening of disease within 12 months prior to Screening and while on treatment with a high-efficacy DMT for at least 6 months.

- Progressive forms of MS - Cohort 2.

i) Participants must have an EDSS ≥ 3.0 and ≤ 6.0.

ii) Participants must have a diagnosis of primary progressive multiple sclerosis (PPMS) that is treatment-resistant or diagnosis of inactive secondary progressive multiple sclerosis (iSPMS).

- Myasthenia Gravis - Cohort 3

i)MGFA classification of II-IV at screening

ii) Documentation of autoantibodies against AChR or MuSK (historical or at Screening)

iii) Refractory disease defined as disease activity on at least 2 immunosuppressants, including steroids, NSIs, or biologics.

iv) Has had thymectomy, only if indicated according to current guidelines.

Exclusion Criteria

* Cohorts 1 and 2: Participants that cannot complete the 9-Hole Peg Test (9-HPT) in at least 1 hand in \<240 seconds unless extenuating medical conditions unrelated to MS prohibit this.
* Participants that cannot perform a Timed 25-Foot Walk Test (T25FWT) in \< 150 seconds.
* Presence of other confounding peripheral nervous system disorders or other disorders that may impact muscle strength (eg, myositis) or cause weakness, stroke, chronic inflammatory demyelinating polyradiculoneuropathy, Lambert-Eaton myasthenic syndrome.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to week 104
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to week 104
measure: Number of participants with adverse events of special interest (AESIs)
timeFrame: Up to week 104
measure: Number of participants with laboratory test result abnormalities
timeFrame: Up to week 104
measure: Number of participants with imaging abnormalities
timeFrame: Up to week 104
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to week 104
measure: Recommended Phase 2 dose (RP2D) based on the incidence of DLTs that occur during the DLT evaluation period
timeFrame: Up to week 104
Secondary outcomes:
measure: Number of participants meeting no evidence of disease activity (NEDA) criteria
timeFrame: Up to week 104
measure: Number of participants with confirmed disability progression per Expanded Disability Status Scale (EDSS)
timeFrame: Up to week 12
measure: Annualized relapse rate
timeFrame: Up to week 104
measure: Change from baseline in magnetic resonance imaging (MRI) metrics
timeFrame: Up to week 104
measure: Number of participants with disability improvement confirmed per EDSS
timeFrame: Up to week 12
measure: Maximum observed blood concentration (Cmax)
timeFrame: Up to week 104
measure: Time of maximum observed blood concentration (Tmax)
timeFrame: Up to week 104
measure: Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D))
timeFrame: Up to week 104
measure: Time to last measurable chimeric antigen receptor (CAR T) concentrations (Tlast)
timeFrame: Up to week 104
measure: Number of participants with at least 2 points improvement for at least 4 weeks in Myasthenia Gravis activities of daily living (MG-ADL) score
timeFrame: Up to week 26
measure: Number of participants with at least 3 point improvement in Myasthenia Gravis composite (MG-C) score
timeFrame: Up to week 26
measure: Number of participants with at least 3 point improvement in quantitative Myasthenia Gravis (QMG) score
timeFrame: Up to week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Local Institution - 0039
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0042
state: New York
city: New York
country: United States
facility: Neurological Institute of New York
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0043
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0037
state: Oregon
city: Philadelphia
country: United States
facility: Local Institution - 0021
state: Pennsylvania
city: Dallas
country: United States
facility: Local Institution - 0006
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edegem
country: Belgium
facility: Local Institution - 0040
state: Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Lille
country: France
facility: Hopital Claude Huriez - CHU de Lille
state: Nord
city: Paris
country: France
facility: Pitie Salpetriere University Hospital
state: Ville De Paris
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: München
country: Germany
facility: Klinikum der Universität München Großhadern
city: Milano
country: Italy
facility: Local Institution - 0008
state: Lombardia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Local Institution - 0016
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Catalunya [Cataluña]
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad De
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: London
country: United Kingdom
facility: University College London Hospital
state: London, City Of
city: Salford
country: United Kingdom
facility: Salford Royal Hospital
state: Manchester
city: London
country: United Kingdom
facility: Local Institution - 0020
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: