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)

Juno Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Myasthenia Gravis; Multiple Sclerosis

Treatments: Drug: Cyclophosphamide; Drug: CC-97540; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT06220201

CA061-1006

2023-507820-22 (Other Identifier)

U1111-1296-8579 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Administration of CC-97540 (RMS arm)

Experimental group

Treatment:

Drug: Fludarabine

Drug: CC-97540

Drug: Cyclophosphamide

Administration of CC-97540 (PMS arm)

Experimental group

Treatment:

Drug: Fludarabine

Drug: CC-97540

Drug: Cyclophosphamide

Administration of CC-97540 (MG arm)

Experimental group

Treatment:

Drug: Fludarabine

Drug: CC-97540

Drug: Cyclophosphamide