Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03283826
Other study ID # ATA188-MS-101
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date October 19, 2017
Est. completion date January 17, 2024

Study information

Verified date February 2024
Source Atara Biotherapeutics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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]).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 134
Est. completion date January 17, 2024
Est. primary completion date November 9, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 60 Years
Eligibility Inclusion Criteria: - 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 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, 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 - 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 ß, 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 ß, 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

Study Design


Related Conditions & MeSH terms

  • Multiple Sclerosis
  • Multiple Sclerosis, Chronic Progressive
  • Primary Progressive Multiple Sclerosis
  • Sclerosis
  • Secondary Progressive Multiple Sclerosis

Intervention

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

Locations

Country Name City State
Australia Royal Brisbane and Women's Hospital Brisbane Queensland
Australia Liverpool Hospital Liverpool New South Wales
Australia Griffith University, School of Medicine Southport Queensland
Canada Fraser Health Multiple Sclerosis Clinic Burnaby British Columbia
Canada Recherche Sepmus Inc. Greenfield Park Quebec
Canada Unity Health Toronto/St. Michael's Hospital Toronto Ontario
United States Dent Neurologic Institute Amherst New York
United States University of Colorado Aurora Colorado
United States Advanced Neurology Fort Collins Colorado
United States Fort Wayne Neurological Center Fort Wayne Indiana
United States Advanced Neurosciences Institute ANI - Franklin Franklin Tennessee
United States Premier Neurology P.C. Greer South Carolina
United States The University of Texas Health Science Center at Houston Houston Texas
United States University of Kansas Medical Center KUMC - Multiple Sclerosis MS Center Kansas City Kansas
United States University of California, San Diego La Jolla California
United States Kaiser Permanente MS Clinic Los Angeles Los Angeles California
United States Neurology Associates, PA-Maitland Maitland Florida
United States Medical College of Wisconsin Milwaukee Wisconsin
United States PMG Research of Piedmont Healthcare Mooresville North Carolina
United States Vanderbilt Comprehensive Multiple Sclerosis Center Nashville Tennessee
United States Ochsner Clinic Foundation New Orleans Louisiana
United States Columbia University Medical Center-The Neurological Institute of New York New York New York
United States Stanford University Palo Alto California
United States University of Pennsylvania Philadelphia Pennsylvania
United States University of Rochester Medical Center - URMC Rochester New York
United States Washington University in St. Louis Saint Louis Missouri
United States University of California San Francisco San Francisco California
United States Inland Northwest Research LLC Spokane Washington
United States University of South Florida, Morsani College of Medicine Tampa Florida
United States MS Center of Greater Washington Vienna Virginia
United States Dragonfly Research Wellesley Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Atara Biotherapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (2)

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. Erratum In: Clin Transl Immunology. 2017 Jun 16;6(6):e147. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Change from baseline in cervical spinal cord volume on MRI scans At 12 months after the first dose of study drug
Other Change from baseline in whole brain volume on MRI scans At 12 months after the first dose of study drug
Other Change from baseline in number of Gd-enhancing and new or enlarging T2 lesions on brain MRI scans At 12 months after the first dose of study drug
Other Change from baseline in IgG production At 12 months after the first dose of study drug
Primary Part 1: Incidence of adverse events At 12 months after the first dose of study drug
Primary Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs At 12 months after the first dose of study drug
Primary Part 1: Recommended Part 2 dose of ATA188 monotherapy Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year)
Primary Part 2: Percentage of participants with confirmed expanded disability status scale (EDSS) improvement at 12 months At 12 months after the first dose of study drug
Secondary Part 1: Change from baseline in EDSS score At 12 months after the first dose of study drug
Secondary Part 2: Percentage of participants with confirmed EDSS improvement at 15 months At 15 months after the first dose of study drug
Secondary 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 At 12 months after the first dose of study drug
Secondary Part 2: Percentage of participants with SDI at 15 months At 15 months after the first dose of study drug
Secondary Part 2: Change from baseline in immunoglobulin G (IgG) index At 9 months after the first dose of study drug
See also
  Status Clinical Trial Phase
Completed NCT04239664 - Acceptance Based Telephone Support When Transitioning to SPMS N/A
Active, not recruiting NCT04411641 - Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) Phase 3
Completed NCT02549703 - Mitochondrial Dysfunction and Disease Progression
Terminated NCT01416181 - A Clinical Study of the Efficacy of Natalizumab on Reducing Disability Progression in Participants With Secondary Progressive Multiple Sclerosis Phase 3
Withdrawn NCT01181089 - Dose Escalation Study to Evaluate the Penetration and Pharmacodynamic Effects of Baminercept in the Cerebrospinal Fluid (CSF)and Safety in Subjects With Secondary Progressive Multiple Sclerosis (SPMS) Phase 1/Phase 2
Active, not recruiting NCT03471338 - Neuropsychological Management of Multiple Sclerosis: Benefits of a Computerised Semi-autonomous At-home Cognitive Rehabilitation Programme N/A
Withdrawn NCT05029609 - Phase 1b Multiple Ascending Dose Study of Foralumab in Primary and Secondary Progressive MS Phase 1
Completed NCT02228213 - Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis Phase 2
Terminated NCT02296346 - Open-Label Study to Evaluate the Efficacy of ECP in Secondary Progressive Multiple Sclerosis N/A
Completed NCT00559702 - Safety Study of Natalizumab to Treat Multiple Sclerosis (MS) Phase 1
Completed NCT02253264 - A Phase 1 Trial of Intrathecal Rituximab for Progressive Multiple Sclerosis Patients Phase 1
Completed NCT01737372 - A Pilot Study to Assess microRNA Biomarkers in Early and Later Stage Multiple Sclerosis N/A
Completed NCT00257855 - A Randomised Controlled Trial of Neuroprotection With Lamotrigine in Secondary Progressive Multiple Sclerosis Phase 2
Recruiting NCT06292923 - A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients Phase 2
Active, not recruiting NCT01228396 - AIMSPRO in the Treatment of Bladder Dysfunction in Secondary Progressive Multiple Sclerosis Phase 2
Completed NCT03896217 - Simvastatin in Secondary Progressive Multiple Sclerosis Phase 2
Completed NCT02495766 - Autologous Mesenchymal Stromal Cells for Multiple Sclerosis Phase 1/Phase 2
Completed NCT00813969 - Autologous Mesenchymal Stem Cell (MSC) Transplantation in MS Phase 1
Completed NCT01077466 - Natalizumab Treatment of Progressive Multiple Sclerosis Phase 2
Terminated NCT00146159 - Study Evaluating Mitoxantrone in Multiple Sclerosis Phase 3