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Phase 1 Study to Evaluate the Safety of ATA188 in Subjects With Progressive and Relapsing-Remitting Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03283826
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Atara Biotherapeutics

Brief Summary:
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 or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis Biological: ATA188 Phase 1

Detailed Description:

This is a multicenter, open-label, two-population, single-arm study with a sequential, interpatient 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]). Following the third dose of both treatment cycles, subjects will undergo a 20-day observation period. After completion of cycle 2, 20-day observation period, 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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
Actual Study Start Date : October 19, 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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]). Following the third dose of both treatment cycles, subjects will undergo a 20-day observation period. After completion of cycle 2, 20-day observation period, 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.
Biological: ATA188
Allogeneic EBV-directed T-cell therapy
Other Names:
  • EBV-CTLs
  • Epstein-Barr Virus-directed cytotoxic T lymphocytes (CTLs)
  • EBV-targeted T-cell




Primary Outcome Measures :
  1. 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

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


Secondary Outcome Measures :
  1. 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

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

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

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 for the diagnosis of MS.

    a. Subjects with RRMS must have failed a health authority approved treatment

  2. Positive EBV serology
  3. 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
  4. 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
  5. 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, (in order of increasing washout period) as follows:

    1. Treatment with corticosteroids within 2 weeks of providing informed consent
    2. Treatment with glatiramer acetate or IFNβ within 4 weeks of providing informed consent
    3. Treatment with dimethyl fumarate within 4 weeks of providing informed consent
    4. Treatment with a B-cell depleting agent within 6 months of providing informed consent
    5. Treatment with methotrexate, azathioprine, or cyclosporine within 6 months of providing informed consent
    6. Treatment with fingolimod within 9 months of providing informed consent
    7. Treatment with natalizumab within 12 months of providing informed consent
    8. Treatment with teriflunomide within 12 months of providing informed consent unless patient has completed an accelerated clearance with cholestyramine
    9. Treatment with mitoxantrone, cyclophosphamide, cladribine, or any other immunosuppressant or cytotoxic therapy within 12 months of providing informed consent, or determined by the investigator to have residual immune suppression from these treatments
    10. Any previous treatment with alemtuzumab
  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

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
United States, Louisiana
The NeuroMedical Center Clinic Recruiting
Baton Rouge, Louisiana, United States, 70817
Contact: Danielle Bryant, BS, LPN    225-768-2040    danielle.bryant@intrafusion.com   
Principal Investigator: April Erwin, MD         
United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Theresa K Dancsak, MSN, RN    713-704-4137    Theresa.Dancsak@uth.tmc.edu   
Principal Investigator: John W Lindsey, MD         
Australia, New South Wales
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Susanne Baker    61(0)296164687    Sue.Baker1@health.nsw.gov.au   
Principal Investigator: Suzanne Hodgkinson, MB, BS, PhD         
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         
Griffith University, School of Medicine Recruiting
Southport, Queensland, Australia, 4222
Contact: Sofia J Sanchez    61(0)756780750    s.jimenezsanchez@griffith.edu.au   
Principal Investigator: Simon A Broadley, MBBS, PhD         
Sponsors and Collaborators
Atara Biotherapeutics
Investigators
Study Director: Tap Maniar, MD Atara Biotherapeutics
Study Director: Kanya Rajangam, MD, PhD Atara Biotherapeutics

Publications:
Responsible Party: Atara Biotherapeutics
ClinicalTrials.gov Identifier: NCT03283826     History of Changes
Other Study ID Numbers: ATA188-MS-101
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018
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