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Primary Progressive Multiple SclerosisPhase 1/2EMBOLDNCT03283826

Phase 1/2 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis

A Phase 1/2 study testing ATA188 in people with Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Atara Biotherapeutics at 31 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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 (RP2D) of ATA188 as monotherapy in Part 1, and to evaluate the effect of ATA188 treatment on clinical disability, as assessed by confirmed Expanded Disability… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
ATA188
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
134 participants
Where
31 sitesin 3 countries
Study dates
19 Oct 2017to 17 Jan 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • For Part 1: History of progressive forms of MS (PPMS or SPMS), as defined by the 2010 Revised McDonald criteria for the diagnosis of MS
  • For Part 1: 18 to < 66 years of age
  • For Part 1: EDSS scores of 3.0 to 7.0. Participants with EDSS scores of 6.5 to 7.0 must retain measurable upper limb function as assessed by the 9-hole Peg Test (9HPT).
  • For Part 2: Current diagnosis of a progressive form of MS (PPMS or SPMS) as defined by the 2017 Revised McDonald criteria
  • For Part 2:18 to < 61 years of age
  • For Part 2:EDSS scores of 3.0 to 6.5
  • Positive EBV serology
  • Willing and able to provide written informed consent

Who cannot join

  • Clinical relapse as follows: For Part 1: Active clinical relapse between providing informed consent and the first dose of study drug. For Part 2: Documented clinical and/or radiological relapse for 2 years prior to screening, including gadolinium (Gd)-enhancing lesion(s) on any brain MRI scans available during this period (A participant will also be considered ineligible if any clinical and/or radiological relapse is reported between screening and the first dose of study drug.)
  • Concurrent serious uncontrolled or unresolved medical condition, such as infection, limiting protocol compliance or exposing the subject to unacceptable risk
  • Positive serology and/or nucleic acid testing (NAT) for human immunodeficiency virus (HIV), active hepatitis B virus (HBV) infection or carrier status for HBV, active hepatitis C virus (HCV) infection
  • For Part 1: Positive serology for syphilis or human T cell lymphotrophic virus I/II
  • Uncontrolled psychosis, uncontrolled depression or suicide risk, substance dependence, or any other psychiatric condition that may compromise the ability to participate in this trial
  • Clinically significant abnormalities of full blood count, renal function, or hepatic function
Show all 19Show fewer
  • Any contraindication to MRI and/or Gd, eg., any object that is reactive to strong static magnetic, pulsed-gradient fields including any metallic fragments or foreign body (eg, aneurysm clip[s], pacemakers, electronic implants, shunts)
  • Any history of cancer (as exceptions, successfully treated non-melanoma skin cancer or carcinoma in situ of the cervix with a < 5% chance of recurrence within 12 months of providing informed consent are allowed.)
  • Prior therapy with corticosteroids (within 2 weeks before Cycle 1 Day 1)
  • Prior therapy (30 days) B-cell depleting agent (eg, anti-CD20 agents such as ocrelizumab); participant must be progressing despite therapy to be eligible
  • For Part 1: Prior therapy (6 half-lives or 30 days whichever is longer) with cladribine, glatiramer acetate, interferon β, dimethyl fumarate, methotrexate, azathioprine, cyclosporine, fingolimod, natalizumab, teriflunomide, mitoxantrone, cyclophosphamide, any other immunosuppressant or cytotoxic therapy (other than steroids), antithymocyte globulin or similar anti-T-cell antibody therapy, or any other investigational product
  • For Part 1: Any previous treatment with alemtuzumab, ablative stem cell transplant, or EBV T-cell therapy
  • For Part 2: Prior therapy (6 half-lives or 30 days whichever is longer) with IV immunoglobin, plasmapheresis, Bruton's tyrosine kinase inhibitors, all sphingosine 1-phosphate receptor modulators (eg, fingolimod), glatiramer acetate, interferon β, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activators (eg, dimethyl fumarate), methotrexate, azathioprine, cyclosporine, natalizumab, teriflunomide, mitoxantrone, cyclophosphamide, any other immunosuppressant or cytotoxic therapy (other than steroids), antithymocyte globulin or similar anti-T-cell antibody therapy, or any other investigational product
  • For Part 2: Any previous treatment with cladribine, alemtuzumab, ablative stem cell transplant, or EBV T-cell therapy
  • Unresolved reactions from previous therapies that may, in the investigator's opinion, impact the safety of the participant or the conduct of this study
  • Unwilling to use protocol specified contraceptive methods
  • Women who are breastfeeding
  • Pregnancy
  • Inability or unwillingness to comply with study procedures

Trial locations and contacts

31 sites in 3 countries.

31 sites in 3 countries

United States25 sites

  • Dent Neurologic Institute

    Amherst, New York, 14226

  • University of Colorado

    Aurora, Colorado, 80045

  • Advanced Neurology

    Fort Collins, Colorado, 80528

  • Fort Wayne Neurological Center

    Fort Wayne, Indiana, 46825

  • Advanced Neurosciences Institute ANI - Franklin

    Franklin, Tennessee, 37064

  • Premier Neurology P.C.

    Greer, South Carolina, 29650

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • University of Kansas Medical Center KUMC - Multiple Sclerosis MS Center

    Kansas City, Kansas, 66160

  • University of California, San Diego

    La Jolla, California, 92037

  • Kaiser Permanente MS Clinic Los Angeles

    Los Angeles, California, 90027

  • Neurology Associates, PA-Maitland

    Maitland, Florida, 32751

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • PMG Research of Piedmont Healthcare

    Mooresville, North Carolina, 28117

  • Vanderbilt Comprehensive Multiple Sclerosis Center

    Nashville, Tennessee, 37215

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • Columbia University Medical Center-The Neurological Institute of New York

    New York, New York, 10032

  • Stanford University

    Palo Alto, California, 94304

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104-5127

  • University of Rochester Medical Center - URMC

    Rochester, New York, 14642

  • University of California San Francisco

    San Francisco, California, 94158

  • Inland Northwest Research LLC

    Spokane, Washington, 99202

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • University of South Florida, Morsani College of Medicine

    Tampa, Florida, 33612

  • MS Center of Greater Washington

    Vienna, Virginia, 22182

  • Dragonfly Research

    Wellesley, Massachusetts, 02481

Other trials in United States

Australia3 sites

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4029

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Griffith University, School of Medicine

    Southport, Queensland, 4222

Other trials in Australia

Canada3 sites

  • Fraser Health Multiple Sclerosis Clinic

    Burnaby, British Columbia, V5G 2X6

  • Recherche Sepmus Inc.

    Greenfield Park, Quebec, J4V2J2

  • Unity Health Toronto/St. Michael's Hospital

    Toronto, Ontario, M5B1W8

Other trials in Canada

About this study

Official title: A Phase 1/2, Two-part, Open-label Dose-escalation and Double-blind, Placebo-controlled Dose-expansion Study With an Open-label Extension to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis

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 (RP2D) of ATA188 as monotherapy in Part 1, and to evaluate the effect of ATA188 treatment on clinical disability, as assessed by confirmed Expanded Disability Status Scale (EDSS) improvement at 12 months in Part 2 in participants with progressive forms of multiple sclerosis (MS) (primary progressive multiple sclerosis [PPMS] and secondary progressive multiple sclerosis [SPMS]).

Read the detailed description

This is a multicenter, 2 part study in adult participants with progressive forms of MS (PPMS/SPMS) with an open-label, single-arm, sequential dose-escalation period (Part 1) and a double-blind, randomized, placebo-controlled dose-expansion period (Part 2) followed by open-label extension (OLE) period. Part 2 and the OLE have been initiated by the sponsor's discretion based on a review of data from the dose-escalation cohorts.

This study will evaluate the safety and efficacy of ATA188 administered by intravenous (IV) infusion. ATA188 will be selected for each participant based on matching 2 or more human leukocyte antigen (HLA) alleles shared between ATA188 and the participant, at least 1 of which is a HLA-restricting allele.

In Part 1, participants received 2 cycles of ATA188 and entered 12 months follow-up period after the last dose of ATA188. Participants who completed at least the first year of the dose-escalation period and were active in the study have entered the OLE period. In OLE period, participants will receive the same RP2D assigned to Part 2 participants at the time of the Part 1 participant's first dose in each year of the OLE. In OLE period, participants will receive 1 cycle of ATA188 treatment every 12 months (Q12M) for up to 4 years (ie, Years 2 to 5). Otherwise, end of study (EOS) visit will be conducted at 24 months after Cycle 1 Day 1.

In Part 2, participants will be randomized in 1:1 ratio to receive ATA188 at the RP2D or matching placebo, stratified by progressive MS diagnosis (PPMS vs SPMS) and any prior exposure to anti-CD20 therapy (yes vs no). Participants will receive 2 cycles of ATA188 at the RP2D or matching placebo and will be followed for at least 12 months after the first dose of study drug (ie, Year 1). In second year (Year 2), participants who received placebo in Year 1 will receive 2 cycles of ATA188 at the RP2D assigned at randomization and participants who received ATA188 at the RP2D in Year 1 will receive 1 cycle of ATA188 (at the RP2D assigned at randomization) and 1 cycle of placebo to maintain the blind. Participants who complete Year 2 will enter the OLE period to receive ATA188 Q12M for up to 3 years (ie, Years 3 to 5) at the RP2D that was last selected by the sponsor for Part 2. The end of study visit will be scheduled at 5 years (60 months) after the first dose of study drug (ie, Cycle 1 Day 1).

Based on interim analysis, the recruitment for Parts 1and 2 have completed.

Being tested
ATA188, Placebo
Keywords
Multiple Sclerosis (MS), Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Epstein-Barr Virus (EBV), EBV-associated Multiple Sclerosis, Inflammation, Central Nervous System, Autoimmune Disease, Autoimmunity, Demyelination, Cell Therapy, T-cell, Allogeneic, EBV viremia, Off-the-shelf (T cells)
Medical subject headings
Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Epstein-Barr Virus Infections, Inflammation, Autoimmune Diseases, Demyelinating Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATA188Biological

    Also called Epstein-Barr Virus-directed cytotoxic T lymphocytes (CTLs), EBV-CTLs, EBV-targeted T-cell

    ATA188 is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ progressive multiple sclerosis.

  • PlaceboDrug

    Placebo matching to ATA188

Study groups in NCT03283826
Study groupRoleWhat they receive
ATA188ExperimentalParticipants in Parts 1 and 2 will receive ATA188 intravenously as described in the Detailed Description.
Receives: Biological: ATA188
PlaceboPlacebo comparatorParticipants 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Incidence of adverse events

    Measured: At 12 months after the first dose of study drug

  2. Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs

    Measured: At 12 months after the first dose of study drug

  3. Part 1: Recommended Part 2 dose of ATA188 monotherapy

    Measured: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year)

  4. Part 2: Percentage of participants with confirmed expanded disability status scale (EDSS) improvement at 12 months

    Measured: At 12 months after the first dose of study drug

Secondary outcomes (5)

  1. Part 1: Change from baseline in EDSS score

    Measured: At 12 months after the first dose of study drug

  2. Part 2: Percentage of participants with confirmed EDSS improvement at 15 months

    Measured: At 15 months after the first dose of study drug

  3. Part 2: Percentage of participants with sustained disability improvement (SDI; ie, confirmed EDSS improvement or 20% decrease in timed 25-foot walk [T25W]) at 12 months

    Measured: At 12 months after the first dose of study drug

  4. Part 2: Percentage of participants with SDI at 15 months

    Measured: At 15 months after the first dose of study drug

  5. Part 2: Change from baseline in immunoglobulin G (IgG) index

    Measured: At 9 months after the first dose of study drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2017
  2. Study start19 Oct 2017
  3. Primary completion9 Nov 2023
  4. Study completion17 Jan 2024

Why it stopped: Study was terminated as primary endpoint was not achieved

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03283826
Sponsor's protocol ID
ATA188-MS-101
Other IDs
NCT03283826
Acronym
EMBOLD
Status last verified
Feb 2024
First submitted
13 Sep 2017
Last updated
23 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Pender MP, Csurhes PA, Smith C, Beagley L, Hooper KD, Raj M, Coulthard A, Burrows SR, Khanna R. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014 Oct;20(11):1541-4. doi: 10.1177/1352458514521888. Epub 2014 Feb 3.

    PubMed 24493474

  • Pender MP, Csurhes PA, Burrows JM, Burrows SR. Defective T-cell control of Epstein-Barr virus infection in multiple sclerosis. Clin Transl Immunology. 2017 Jan 20;6(1):e126. doi: 10.1038/cti.2016.87. eCollection 2017 Jan.

    PubMed 28197337

  • Drosu N, Bjornevik K, Bilodeau PA, Yeh A, Lechner-Scott J, Hawkes CH, Giovannoni G, Levy M. In the era of antiviral trials for MS, the answer lies in the details. Mult Scler Relat Disord. 2024 Feb;82:105444. doi: 10.1016/j.msard.2024.105444. Epub 2024 Jan 12. No abstract available.

    PubMed 38241758

  • Giovannoni G, Hawkes CH, Lechner-Scott J, Levy M, Yeh EA. Emboldened or not: The potential fall-out of a failed anti-EBV trial in multiple sclerosis. Mult Scler Relat Disord. 2024 Jan;81:105364. doi: 10.1016/j.msard.2023.105364. Epub 2023 Dec 10. No abstract available.

    PubMed 38104476

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ATA188 in people with Primary Progressive Multiple Sclerosis and Secondary Progressive Multiple Sclerosis, run by Atara Biotherapeutics at 31 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Study was terminated as primary endpoint was not achieved). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Incidence of adverse events (time frame: At 12 months after the first dose of study drug). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03283826, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2024.

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