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Trial record 1 of 1 for:    ata188
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Phase 1 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03283826
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : July 31, 2020
Sponsor:
Information provided by (Responsible Party):
Atara Biotherapeutics

Brief 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 biological markers of disease activity in cerebral spinal fluid in Part 2 in participants with progressive forms of multiple sclerosis (MS) (primary progressive multiple sclerosis [PPMS] and secondary progressive multiple sclerosis [SPMS]).

Condition or disease Intervention/treatment Phase
Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis Biological: ATA188 Drug: Placebo Phase 1

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) and open-label extension (OLE) period, both of which may be initiated at 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 at least 2 human leukocyte antigen (HLA) alleles shared between ATA188 and the participant including at least 1 HLA-restricting allele.

In Part 1, participants will receive 2 cycles of ATA188 and will enter 12 months follow-up period after the last dose of ATA188. Participants who have completed at least the first year of the dose-escalation period and are still active in the study may be allow to enter in "Open-label Extension" period and will receive the same RP2D dose being assigned to Part 2 participants. In "Open-label Extension" 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 5:4 ratio to receive ATA188 at the RP2D or matching placebo. Based on a review of available data, up to 36 additional participants may be randomized 2:1 to ATA188 or placebo. 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 first year will receive 2 cycles of ATA188 at the RP2D assigned at randomization and participants who received ATA188 at the RP2D in first year will receive 1 cycle of ATA188 and 1 cycle of placebo. Participants who complete Year 2 will enter in OLE period to receive ATA188 Q12M for up to 3 years (ie, Years 3 to 5) at the RP2D received in the double-blind period (Year 1 and Year 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, 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
Actual Study Start Date : October 19, 2017
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : February 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ATA188
Participants will receive ATA188 intravenously.
Biological: ATA188
ATA188 is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ progressive multiple sclerosis.
Other Names:
  • Epstein-Barr Virus-directed cytotoxic T lymphocytes (CTLs)
  • EBV-CTLs
  • EBV-targeted T-cell

Placebo Comparator: Placebo
Participants will receive placebo matching to ATA188 intravenously.
Drug: Placebo
Placebo matching to ATA188




Primary Outcome Measures :
  1. Part 1 and Part 2: Incidence of adverse events [ Time Frame: At 12 months after the first dose of study drug ]
    Safety and tolerability

  2. Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs [ Time Frame: At 12 months after the first dose of study drug ]
  3. Part 1: Recommended Part 2 dose of ATA188 monotherapy [ Time Frame: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year) ]
    Dose assessment

  4. Part 2: Change from baseline in immunoglobulin G (IgG) index, including quantification of IgG production [ Time Frame: At 12 months after the first dose of study drug ]
    Antibody assessment and quantification


Secondary Outcome Measures :
  1. Part 1: Change from baseline in expanded disability status scale (EDSS) score [ Time Frame: At 12 months after the first dose of study drug ]
    Changes in disability score

  2. Part 2: Change from baseline in clinical disability as assessed by the EDSS score and/or Timed 25 foot Walk (T25W) and/or 9-hole Peg Test (9HPT) [ Time Frame: At 12 months after the first dose of study drug ]
    Changes in disability score

  3. Part 2: Change from baseline in cervical spinal cord volume and whole brain volume on MRI scans [ Time Frame: At 12 months after the first dose of study drug ]
    Change in MRI activity

  4. Part 2: Change from baseline in the number of Gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans [ Time Frame: At 12 months after the first dose of study drug ]
    Change in MRI activity



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Positive EBV serology
  • 18 to < 66 years of age for Part 1 and 18 to < 56 years of age for Part 2
  • History of progressive forms of MS as defined by the 2010 Revised McDonald criteria for the diagnosis of MS for Part 1
  • Current diagnosis of a progressive form of MS as defined by the 2017 Revised McDonald criteria for Part 2
  • EDSS scores of 3.0 to 7.0 for Part 1 and EDSS scores of 3.0 to 6.5 for Part 2

Exclusion Criteria:

• 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
  • 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
  • Positive serology for syphilis or human T cell lymphotrophic virus I/II (HTLV)
  • Clinically significant abnormalities of full blood count, renal function, or hepatic function
  • 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)
  • Prior therapy with corticosteroids (2 weeks before Cycle 1 Day 1)
  • Prior therapy (6 half-lives or 30 days, whichever is longer) with glatiramer acetate, interferon (IFN) β, dimethyl fumarate, B-cell depleting agent, 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 Parts 1 and 2, and cladribine for Part 1 and IV immunoglobin, plasmapheresis, Bruton's tyrosine kinase inhibitors, all sphingosine 1-phosphate receptor modulators for Part 2
  • Previous treatment with alemtuzumab, stem cell transplant, or EBV T-cell therapy for both parts and cladribine for Part 2
  • Unwilling to use protocol specified contraceptive methods
  • Women who are breastfeeding
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283826


Contacts
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Contact: Study Director 650-278-8930 clinicalstudies@atarabio.com

Locations
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United States, Arizona
Mayo Clinic Withdrawn
Scottsdale, Arizona, United States, 85259-5452
United States, Louisiana
The NeuroMedical Center Clinic, PC Withdrawn
Baton Rouge, Louisiana, United States, 70810-1685
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Bridget Bagert, MD    504-703-7458    bbagert@ochsner.org   
United States, North Carolina
PMG Research of Piedmont Healthcare Recruiting
Mooresville, North Carolina, United States, 28117
Contact: Craig Dubois, MD    704-235-1834    nerissa.lowery@pmg-research.com   
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-5127
Contact: Amit Bar-Or, MD, FRCP, FAAN, FANA    215-220-9384    amitbar@pennmedicine.upenn.edu   
United States, Tennessee
Advanced Neurosciences Institute ANI - Franklin Recruiting
Franklin, Tennessee, United States, 37064
Contact: Samuel Hunter    615-794-5470    frontdesk@neurosci.us   
United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: John Lindsey, MD    832-325-7082    john.w.lindsey@uth.tmc.edu   
United States, Washington
Inland Northwest Research LLC Recruiting
Spokane, Washington, United States, 99202
Contact: Steven Pugh, MD    509-960-2818    spugh@inwresearch.com   
Australia, New South Wales
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Suzanne Hodgkinson, BSc, MB, BSFRACP, PhD    +61(0) 2 96164689    s.hodgkinson@unsw.edu.au   
Australia, Queensland
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4006
Contact: Michael K Pender, MD, PhD, FRACP, MBBS    +61 (0) 7 3365 5132    m.pender@uq.edu.au   
Griffith University, School of Medicine Recruiting
Southport, Queensland, Australia, 4222
Contact: Simon J Broadley, BSc, MBChB, PhD, FRACP    +61 (0) 7 567 80174    simon.broadley@griffith.edu.au   
Sponsors and Collaborators
Atara Biotherapeutics
Investigators
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Study Director: Kiren Kresa-Reahl, MD Atara Biotherapeutics
Publications:
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Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03283826    
Other Study ID Numbers: ATA188-MS-101
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: July 31, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Atara Biotherapeutics:
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)
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases