Purpose

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 Phase 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]).

Conditions

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

  • Active clinical relapse between providing informed consent 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

The University of Texas Health Science Center at Houston
Houston, Texas 77030
Contact:
John Lindsey, MD
832-325-7082
john.w.lindsey@uth.tmc.edu

More Details

Status
Recruiting
Sponsor
Atara Biotherapeutics

Study Contact

Jonathan Willmer, MD
805-623-4221
clinicalstudies@atarabio.com

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. 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 for 2 cycles 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 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 at the RP2D Q12M for up to 3 years (ie, Years 3 to 5). 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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.