Multiple Sclerosis, Myasthenia Gravis
Conditions
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
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).
Interventions
DRUGCC-97540
Specified dose on specified days
DRUGFludarabine
Specified dose on specified days
DRUGCyclophosphamide
Specified dose on specified days
Sponsors
Juno Therapeutics, Inc., a Bristol-Myers Squibb Company
Celgene Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | Up to week 104 | — |
| Number of participants with serious adverse events (SAEs) | Up to week 104 | — |
| Number of participants with adverse events of special interest (AESIs) | Up to week 104 | — |
| Number of participants with laboratory test result abnormalities | Up to week 104 | — |
| Number of participants with imaging abnormalities | Up to week 104 | For Cohorts 1 and 2 |
| Number of participants with dose-limiting toxicities (DLTs) | Up to week 104 | — |
| Recommended Phase 2 dose (RP2D) based on the incidence of DLTs that occur during the DLT evaluation period | Up to week 104 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants meeting no evidence of disease activity (NEDA) criteria | Up to week 104 | — |
| Number of participants with confirmed disability progression per Expanded Disability Status Scale (EDSS) | Up to week 12 | — |
| Annualized relapse rate | Up to week 104 | — |
| Change from baseline in magnetic resonance imaging (MRI) metrics | Up to week 104 | MRI metrics assessed are 1) number of gadolinium-enhancing T1 lesions and 2) total number of new or enlarging hyperintense T2-weigted lesions |
| Number of participants with disability improvement confirmed per EDSS | Up to week 12 | — |
| Maximum observed blood concentration (Cmax) | Up to week 104 | — |
| Time of maximum observed blood concentration (Tmax) | Up to week 104 | — |
| Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D)) | Up to week 104 | — |
| Time to last measurable chimeric antigen receptor (CAR T) concentrations (Tlast) | Up to week 104 | — |
| Number of participants with at least 2 points improvement for at least 4 weeks in Myasthenia Gravis activities of daily living (MG-ADL) score | Up to week 26 | For Cohort 3 |
| Number of participants with at least 3 point improvement in Myasthenia Gravis composite (MG-C) score | Up to week 26 | For Cohort 3 |
| Number of participants with at least 3 point improvement in quantitative Myasthenia Gravis (QMG) score | Up to week 26 | For Cohort 3 |
Countries
Belgium, France, Germany, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed