CC-97540 for Multiple Sclerosis

Recruiting at 68 trial locations

Overseen By Sharon Lynch, Site 0003

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Must be taking: High-efficacy DMTs, Immunosuppressants

Disqualifiers: Myositis, Stroke, CIDP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called CC-97540 to see if it is safe and effective for people with relapsing or progressive multiple sclerosis. The goal is to find out if it can help manage symptoms or slow down the disease.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants with relapsing forms of MS must have been on a high-efficacy disease-modifying therapy for at least 6 months, suggesting that some medications may need to be continued.

What makes the drug CC-97540 unique for treating multiple sclerosis?

CC-97540 is unique because it targets CD19, a marker found on certain B-cells, which are more prevalent in the cerebrospinal fluid of African American patients with multiple sclerosis. This focus on CD19 distinguishes it from other treatments like rituximab, which targets CD20, another B-cell marker. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with Relapsing or Progressive Forms of Multiple Sclerosis. Specific eligibility details are not provided, but typically participants must meet certain health criteria and may be excluded based on factors that could impact their safety or the results of the study.

Inclusion Criteria

I have MS with recent worsening despite treatment.

I have progressive MS with limited mobility and my condition is treatment-resistant or inactive.

Exclusion Criteria

I do not have MS lesions or symptoms that increase my risk of brain side effects.

I cannot walk 25 feet in less than 150 seconds.

I can complete a hand dexterity test in less than 4 minutes for each hand.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CC-97540 to evaluate safety, tolerability, efficacy, and drug levels

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

78 weeks

Treatment Details

Interventions

• CC-97540
• Cyclophosphamide
• Fludarabine

Trial Overview The study is testing CC-97540, along with Fludarabine and Cyclophosphamide, to assess their safety, tolerability, effectiveness, and levels in the body among those with different forms of Multiple Sclerosis.

Participant Groups

Group I: Administration of CC-97540 (RMS arm) Experimental Treatment 3 Interventions

Group II: Administration of CC-97540 (PMS arm) Experimental Treatment 3 Interventions

Group III: Administration of CC-97540 (MG arm) Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

Lead Sponsor

Trials

19

Recruited

3,100+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

Findings from Research

In a study comparing 20 African-American (AA) and 56 White (W) patients with multiple sclerosis (MS), AA patients showed significantly higher proportions of CD19+ (5.46% vs. 2.26%) and CD20+ (4.64% vs. 1.91%) B-cells in their cerebrospinal fluid (CSF).

The findings suggest that B-cells are overrepresented in the CSF of AA MS patients compared to W patients, which may have implications for understanding disease mechanisms and treatment responses in different racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients. Xue, H., Arbini, AA., Melton, HJ., et al.[2023]

Intrathecal delivery of rituximab in 23 patients with progressive multiple sclerosis was generally well tolerated, with only mild to moderate side effects like vertigo and nausea, although there was a risk of severe infections such as bacterial meningitis.

After one year of treatment, there was minimal evidence of clinical improvement or changes in cerebrospinal fluid biomarkers, indicating that while the treatment is feasible, its efficacy remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study. Bergman, J., Burman, J., Gilthorpe, JD., et al.[2019]

In a 36-week extension study involving 257 patients with relapsing-remitting MS, laquinimod demonstrated sustained efficacy by significantly reducing MRI-measured disease activity, particularly in patients who switched from placebo to treatment, with a 52% reduction in gadolinium-enhanced lesions.

The safety profile of laquinimod was confirmed, with the most notable side effect being reversible elevations in liver enzymes, indicating that it is well-tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study. Comi, G., Abramsky, O., Arbizu, T., et al.[2014]

Alemtuzumab, a humanized monoclonal antibody targeting CD52, has been approved for treating multiple sclerosis (MS) in Europe and is effective in long-term depletion of B and T cells, which helps reduce neurological deficits.

Clinical trials (phase 2 and 3) show that alemtuzumab significantly lowers the risk of sustained neurological decline compared to high-dose interferon-β1a in patients with active relapsing-remitting MS, whether they are treatment-naïve or experiencing breakthrough disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[ALEMTUZUMAB: BENEFITS AND CHALLENGES OF A NEW THERAPY IN MULTIPLE SCLEROSIS]. Illés, Z., Sejbaek, T., Csépány, T.[2019]

In a study of 90 patients with relapsing-remitting and progressive multiple sclerosis, rituximab treatment led to an impressive 88.4% reduction in the annualized relapse rate and a significant decrease in disability status after one year.

Rituximab was found to be generally safe, with mild infusion-related symptoms being the most common side effect, although three thrombotic events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study. Alcalá, C., Gascón, F., Pérez-Miralles, F., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Intrathecal treatment trial of rituximab in progressive MS: An open-label phase 1b study. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Oral laquinimod in patients with relapsing-remitting multiple sclerosis: 36-week double-blind active extension of the multi-centre, randomized, double-blind, parallel-group placebo-controlled study. [2014]

4. Hungary pubmed.ncbi.nlm.nih.gov

[ALEMTUZUMAB: BENEFITS AND CHALLENGES OF A NEW THERAPY IN MULTIPLE SCLEROSIS]. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study. [2022]