ATA188 for Multiple Sclerosis

(EMBOLD Trial)

Recruiting at 35 trial locations

Overseen By Study Director

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Atara Biotherapeutics

Must not be taking: Corticosteroids, B-cell depleting, others

Disqualifiers: HIV, Hepatitis, Cancer, others

Compensation: Varies

Number of Visits: Unknown

134 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests ATA188, a treatment given through a vein, in adults with progressive forms of multiple sclerosis. The treatment is customized to each patient's immune system to see if it can improve their condition.

Will I have to stop taking my current medications?

The trial requires participants to stop certain medications before starting. For Part 1, you must stop some treatments like corticosteroids 2 weeks before, and other therapies like glatiramer acetate or interferon β for 6 half-lives or 30 days, whichever is longer. For Part 2, similar requirements apply, including stopping IV immunoglobulin and other specific treatments for 6 half-lives or 30 days, whichever is longer.

How does the drug ATA188 differ from other treatments for multiple sclerosis?

ATA188 is unique because it targets the migration and infiltration of immune cells that contribute to the disease, potentially offering a novel approach by blocking chemokine-mediated pathways, unlike other treatments that may focus on different mechanisms. ^{1 2 3 4 5}

Research Team

Kiren Kresa-Reahl, MD

Principal Investigator

Atara Biotherapeutics

Eligibility Criteria

This trial is for adults with progressive forms of multiple sclerosis (PPMS or SPMS) who have certain levels of disability (EDSS scores between 3.0 to 6.5 or up to 7.0 in Part 1). Participants must test positive for EBV and be willing to use contraception if applicable. Excluded are those with recent immunosuppressant treatments, serious medical conditions, pregnancy, breastfeeding women, and anyone unable to follow the study procedures.

Inclusion Criteria

I have a progressive form of multiple sclerosis.

I have been diagnosed with a progressive form of MS.

My disability score is between 3.0 and 7.0, and I can use my hands if it's 6.5 to 7.0.

Exclusion Criteria

Inability or unwillingness to comply with study procedures

I haven't taken corticosteroids in the last 2 weeks.

I haven't taken specific immune or cancer treatments recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation (Part 1)

Participants receive 2 cycles of ATA188 and enter a 12-month follow-up period after the last dose

12 months

Dose-expansion (Part 2)

Participants are randomized to receive ATA188 or placebo for 2 cycles, followed by a 12-month follow-up

12 months

Open-label extension (OLE)

Participants receive 1 cycle of ATA188 every 12 months for up to 4 years

3-4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• ATA188

Trial Overview The trial is testing ATA188's safety and ability to improve clinical disability in MS patients compared with a placebo. It aims to find the best dose in Part 1 and then assess its effectiveness on disability at the one-year mark in Part 2 using EDSS score improvements as a measure.

Participant Groups

Group I: ATA188 Experimental Treatment 1 Intervention

Participants in Parts 1 and 2 will receive ATA188 intravenously as described in the Detailed Description.

Group II: Placebo Placebo Group 1 Intervention

Participants in Part 2 will receive placebo matching to ATA188 intravenously as described in the Detailed Description (i.e., will receive placebo only in the first year, and thereafter will receive ATA188 for the remainder of the study).

Who Is Running the Clinical Trial?

Atara Biotherapeutics

Lead Sponsor

Trials

14

Recruited

740+

Findings from Research

Glatiramer acetate (GA) has been shown to significantly reduce relapse rates and neurological disability in patients with relapsing-remitting multiple sclerosis (MS), with effects maintained over a 10-year period based on the longest prospective study in MS therapeutics.

GA not only has a strong safety profile but also exhibits neuroprotective properties, making it a first-line treatment option for relapsing-remitting MS and a promising candidate for combination therapies in MS and other neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate therapy for multiple sclerosis: a review. Perumal, J., Filippi, M., Ford, C., et al.[2019]

In a 2-year study involving 612 subjects with secondary progressive multiple sclerosis (SPMS), MBP8298 did not show any significant clinical benefit compared to placebo in terms of disease progression or other secondary outcomes.

The treatment was well tolerated with no safety issues reported, indicating that while MBP8298 is safe, it is not effective for patients with SPMS who express the HLA haplotype DR2 or DR4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS. Freedman, MS., Bar-Or, A., Oger, J., et al.[2022]

In a 3-year trial involving 943 patients with primary progressive multiple sclerosis, glatiramer acetate (GA) did not show a significant effect on slowing disability accumulation compared to placebo, as indicated by a hazard ratio of 0.87 (p = 0.1753).

However, post hoc analysis revealed that GA may have beneficial effects in male patients, showing a significant delay in clinical progression compared to placebo, with a hazard ratio of 0.71 (p = 0.0193).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Wolinsky, JS., Narayana, PA., O'Connor, P., et al.[2022]

References

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

Aurintricarboxylic acid ameliorates experimental autoimmune encephalomyelitis by blocking chemokine-mediated pathogenic cell migration and infiltration. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Inhibition of glial cell activation ameliorates the severity of experimental autoimmune encephalomyelitis. [2012]

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

Glatiramer acetate therapy for multiple sclerosis: a review. [2019]

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

A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS. [2022]

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

Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. [2022]