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Trial record 1 of 1 for:    NCT03283826 | Recruiting, Not yet recruiting Studies
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Phase 1 Study to Evaluate the Safety of ATA188 in Subjects With Progressive and Relapsing-Remitting Multiple Sclerosis

This study is currently recruiting participants.
Verified October 2017 by Atara Biotherapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT03283826
First Posted: September 14, 2017
Last Update Posted: October 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Atara Biotherapeutics
  Purpose
This is a multicenter, open-label, two-population, single-arm study with a sequential dose-escalation and dose-expansion in adult subjects with progressive forms of multiple sclerosis (MS) and an in adult subjects with relapsed remitting multiple sclerosis (RRMS).

Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis Drug: ATA188 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Phase 1 Study to Evaluate the Safety of ATA188 in Subjects With Progressive and Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Atara Biotherapeutics:

Primary Outcome Measures:
  • Incidence of adverse events and clinically significant changes in laboratory tests, ECGs, and vital signs [ Time Frame: Approximately 2 months per subject ]
    Safety and tolerability

  • Recommended Phase 2 dose of ATA188 monotherapy [ Time Frame: Approximately 1 year ]
    Dose finding


Secondary Outcome Measures:
  • Change from baseline in the number of Gd-enhancing and new or enlarging T2 lesions on brain MRI scans for subjects with RRMS [ Time Frame: Approximately 9 months per subject ]
    Changes in MRI activity

  • Change from baseline in expanded disability status scale (EDSS) score [ Time Frame: Approximately 9 months per subject ]
    Change in disability

  • Change from baseline in annualized relapse rate (ARR) for subjects with RRMS [ Time Frame: Approximately 9 months per subject ]
    Change in clinical disease activity


Estimated Enrollment: 60
Actual Study Start Date: October 19, 2017
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Progressive or RRMS
Adult subjects with either progressive forms of MS (Population A) or with Relapsing Remitting Multiple Sclerosis (Population B) will be enrolled. Subjects will receive 2 cycles of treatment with each cycle consisting of a 15-day treatment period (with 3 infusions, each given approximately 7 days apart, on Days 1, 8 [±2 days], and 15 [±2 days]). After the third infusion of Cycle 1, subjects will enter a 20-day observation period with weekly visits, and after the third infusion of Cycle 2, subjects will enter a follow-up period with 11 monthly (every 28 ±5 days) visits. Together, subjects will be observed for at least 1 year after the first dose of ATA188.
Drug: ATA188
Allogeneic EBV-directed T-cell therapy
Other Names:
  • EBV-CTLs
  • Epstein-Barr Virus-directed cytotoxic T lymphocytes (CTLs)
  • EBV-targeted T-cell

Detailed Description:

This is a multicenter, open-label, two-population, single-arm study with a sequential dose-escalation and dose expansion in adult subjects with progressive forms of MS (Population A) and in adult subjects with RRMS (Population B).

This study will evaluate the safety of ATA188 administered by intravenous (IV) infusion. ATA188 will be selected for each subject based on matching at least 2 human leukocyte antigen (HLA) alleles shared between ATA188 and the subject including at least 1 HLA-restricting allele.

Subjects will receive 2 cycles of treatment with each cycle consisting of a 15-day treatment period (with 3 infusions, each given approximately 7 days apart, on Days 1, 8 [±2 days], and 15 [±2 days]). After the third infusion of Cycle 1, subjects will enter a 20-day observation period with weekly visits, and after the third infusion of Cycle 2, subjects will enter a follow-up period with 11 monthly (every 28 ±5 days) visits. Together, subjects will be observed for at least 1 year after the first dose of ATA188.

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

A subject will be considered eligible to participate in this study if all of the following are satisfied:

  1. History of MS, with progressive forms of MS or RRMS as defined by the 2010 Revised McDonald criteria [53] for the diagnosis of MS.

    1. Subjects with progressive forms of MS must have no new Gd-enhancing lesions within 12 months of providing informed consent
    2. Subjects with RRMS must have failed a health authority approved treatment
  2. Positive EBV serology
  3. Availability of appropriate partially HLA-matched and restricted ATA188 cell product
  4. Males and females of the following ages:

    1. 18 to 65 years of age for subjects with progressive forms of MS
    2. 18 to 45 years of age for subjects with RRMS
  5. EDSS scores as follows:

    1. 3.0 to 6.5 for subjects with progressive forms of MS
    2. 2.0 to 5.5 for subjects with RRMS
  6. Willing and able to provide written informed consent

Exclusion Criteria:

A subject will not be eligible to participate in the study if any of the following criteria are met:

  1. Active clinical relapse between providing informed consent and enrollment (ie, date of the first dose of ATA188)
  2. Concurrent serious uncontrolled or unresolved medical condition, such as infection, limiting protocol compliance or exposing the subject to unacceptable risk
  3. Positive serology and/or nucleic acid testing (NAT) for human immunodeficiency virus (HIV)
  4. Serology and/or NAT indicating active hepatitis B virus (HBV) infection or carrier status for HBV (Note: A positive serology for HBV indicating a previous but cleared infection with HBV is not an exclusion criterion)
  5. Serology and/or NAT indicating active hepatitis C virus (HCV) infection
  6. Positive serology for syphilis or human T cell lymphotrophic virus I/II (HTLV)
  7. Significant non-malignant disease (eg, severe cardiac or respiratory dysfunction)
  8. Uncontrolled psychosis, uncontrolled depression or suicide risk, substance dependence, or any other psychiatric condition that may compromise the ability to participate in this trial
  9. Clinically significant abnormalities of full blood count, renal function, or hepatic function:

    • Elevated liver function tests, including total bilirubin (TBILI) > 1.5× the upper limit of normal (ULN; unless subject has documented Gilbert's disease), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0×ULN
    • Subjects with both a creatinine > 1.5×ULN and an estimated creatinine clearance of < 60 mL/min (using the Cockcroft-Gault equation)
    • Hemoglobin < 10 g/dL; platelet < 100×109/L; absolute neutrophil count < 1.5×109/L
  10. 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)
  11. Prior cancers, except 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
  12. Immunomodulatory therapy as follows:

    1. Any previous treatment with a B-cell depleting agent
    2. Any previous treatment with alemtuzumab
    3. Treatment with corticosteroids within 2 weeks of providing informed consentTreatment with glatiramer acetate or interferon (IFN)β within 4 weeks of providing informed consent
    4. Treatment with dimethyl fumarate within 4 weeks of providing informed consent
    5. Treatment with fingolimod within 2 months of providing informed consent
    6. Treatment with natalizumab, methotrexate, azathioprine, or cyclosporine within 6 months of providing informed consent
    7. Treatment with teriflunomide within 12 months of providing informed consent unless patient has completed an accelerated clearance with cholestyramine
    8. Treatment with mitoxantrone, cyclophosphamide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids) within 12 months of providing informed consent, or determined by the treating physician to have residual immune suppression from these treatments
  13. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks of providing informed consent
  14. Female of childbearing potential unwilling to use a highly effective method of contraception (ie, one that results in pregnancy less than 1% per year when used consistently and correctly), eg, implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner, and/or unwilling to refrain from donating eggs while undergoing treatment with ATA188 and for 3 months after the last dose OR Men with a female partner of childbearing potential unwilling to use a highly effective contraceptive measure and/or unwilling to refrain from donating sperm while undergoing treatment with ATA188 and for 3 months after the last dose
  15. Women who are breastfeeding
  16. Pregnancy
  17. Inability to comply with study procedures
  18. Previous treatment with EBV T cell therapy
  Contacts and Locations
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
Contact: Atara Biotherapeutics (805) 603-4856 clinicaltrials@atarabio.com

Locations
Australia, Queensland
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: Nanette Douglas    (07) 3646 2548    nanette.douglas@health.qld.gov.au   
Principal Investigator: Michael Pender, MD, PhD         
Sponsors and Collaborators
Atara Biotherapeutics
Investigators
Study Director: Tap Maniar, MD Atara Biotherapeutics
Study Director: Kanya Rajangam, MD, PhD Atara Biotherapeutics
  More Information

Publications:
Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03283826     History of Changes
Other Study ID Numbers: ATA188-MS-101
First Submitted: September 13, 2017
First Posted: September 14, 2017
Last Update Posted: October 23, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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
Relapsing Remitting Multiple Sclerosis
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

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases