ATA188 for Multiple Sclerosis

(EMBOLD Trial)

No longer recruiting at 36 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and benefits of ATA188, an experimental treatment for individuals with progressive forms of multiple sclerosis (MS). The focus is on assessing how well the treatment improves MS-related disability. The trial compares ATA188 to a placebo, which contains no active drug, to determine its effectiveness. Individuals with primary or secondary progressive MS who have experienced worsening symptoms might be suitable candidates for this trial. As a Phase 1/Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that ATA188 is likely to be safe for humans?

Research shows that ATA188 is promising in terms of safety and tolerability. Early studies found no new safety problems in participants who received ATA188. Patients generally tolerated the treatment well, with no unexpected side effects.

These findings suggest that ATA188 could be a safe option for people with progressive forms of multiple sclerosis (MS). Overall, the data so far supports the treatment's safety, but ongoing studies will provide more information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for MS?

Unlike the standard treatments for multiple sclerosis, which often focus on managing symptoms or modulating the immune system, ATA188 targets the Epstein-Barr virus (EBV) infected cells. Researchers are excited about this treatment because it uses specially engineered T-cells to identify and destroy these EBV-infected cells, potentially addressing a root cause of the disease. This unique approach could offer a new avenue for treatment, providing hope for more effective management of multiple sclerosis.

What evidence suggests that ATA188 might be an effective treatment for multiple sclerosis?

Research suggests that ATA188, which participants in this trial may receive, shows promise for treating progressive multiple sclerosis (MS). In earlier studies, some patients demonstrated improvements in their disability over 12 months. Imaging tests indicated that ATA188 could help repair nerve damage in the brain, which is crucial for MS patients. However, another study did not meet its main goal, meaning it didn't achieve the researchers' expectations. These mixed results indicate that more research is needed to fully understand ATA188's potential benefits. ^{2 4 5 6 7}

Who Is on the Research Team?

Kiren Kresa-Reahl, MD

Principal Investigator

Atara Biotherapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. atarabio.com atarabio.com/wp-content/uploads/2023/10/Pub00259_LBPos_EAN_2020_ATA188_Final-1.pdf

Phase 1 Study of the Safety and Efficacy of ATA188, an Off- ... Clinical outcomes were assessed at baseline and approximately 3, 6, and 12 months follow up from initial dose. • The natural history of progressive forms of MS ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03283826

NCT03283826 | Phase 1/2 Study to Evaluate the Safety ... This study will evaluate the safety and efficacy of ATA188 administered by intravenous (IV) infusion. ATA188 will be selected for each participant based on ...

3. neurologylive.com neurologylive.com/view/ata188-fails-meet-primary-end-point-phase-2-embold-study-progressive-ms

ATA188 Fails to Meet Primary End Point In Phase 2 ... The phase 2 EMBOLD study on ATA188, an allogenic T-cell immunotherapy for non-active progressive multiple sclerosis, did not meet its primary endpoint.

4. mscare.org mscare.org/phase-1-2-study-to-evaluate-the-safety-and-efficacy-of-ata188-in-progressive-ms/

Phase 1/2 study to evaluate the safety and efficacy of ... The purpose of this study is to evaluate the safety and tolerability of ATA188 as a monotherapy in Parts 1 and 2, to determine the recommended Part 2 dose ...

5. charcot-ms.org charcot-ms.org/files/30_ECF2021_Poster_CL_Bar-Or_A.pdf

Phase I open-label extension and imaging data for ATA188 ... The nMTR data provide evidence that structural changes suggestive of remyelination may be driving such prolonged sustained improvement. • Although encouraging, ...

6. atarabio.com atarabio.com/wp-content/uploads/2019/09/Pub00071_Abs1026_ECTRIMS_2019_ATA188_Safety_Efficacy_Final.pdf

Preliminary Safety and Efficacy Of ATA188, a Pre- ... The analysis included all subjects who received at least one dose of ATA188 at the time of data snapshot. One patient who had MS relapse at the time of dosing ...

7. investors.atarabio.com investors.atarabio.com/news-events/press-releases/detail/330/atara-biotherapeutics-announces-primary-analysis-data-from

News & Events Preliminary safety data showed there were no new safety signals in the EMBOLD study, reinforcing the favorable safety profile observed with ...