Phase 1/2 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis (EMBOLD)
Primary Progressive Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
About this trial
This is an interventional treatment trial for Primary Progressive Multiple Sclerosis focused on measuring 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)
Eligibility Criteria
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 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
Sites / Locations
- University of California, San Diego
- Kaiser Permanente MS Clinic Los Angeles
- Stanford University
- University of California San Francisco
- University of Colorado
- Advanced Neurology
- Neurology Associates, PA-Maitland
- University of South Florida, Morsani College of Medicine
- Fort Wayne Neurological Center
- University of Kansas Medical Center KUMC - Multiple Sclerosis MS Center
- Ochsner Clinic Foundation
- Dragonfly Research
- Washington University in St. Louis
- Dent Neurologic Institute
- Columbia University Medical Center-The Neurological Institute of New York
- University of Rochester Medical Center - URMC
- PMG Research of Piedmont Healthcare
- University of Pennsylvania
- Premier Neurology P.C.
- Advanced Neurosciences Institute ANI - Franklin
- Vanderbilt Comprehensive Multiple Sclerosis Center
- The University of Texas Health Science Center at Houston
- MS Center of Greater Washington
- Inland Northwest Research LLC
- Medical College of Wisconsin
- Liverpool Hospital
- Royal Brisbane and Women's Hospital
- Griffith University, School of Medicine
- Fraser Health Multiple Sclerosis Clinic
- Unity Health Toronto/St. Michael's Hospital
- Recherche Sepmus Inc.
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
ATA188
Placebo
Participants in Parts 1 and 2 will receive ATA188 intravenously as described in the Detailed Description.
Participants 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).