Phase 1 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis
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 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]).
- Primary Progressive Multiple Sclerosis
- Secondary Progressive Multiple Sclerosis
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Genders
- Accepts Healthy Volunteers
- 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
• 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
- 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
- Phase 1
- Study Type
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Double (Participant, Investigator)
|Participants will receive ATA188 intravenously.||
|Participants will receive placebo matching to ATA188 intravenously.||
- Atara Biotherapeutics
Study ContactStudy Director
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 and will receive the same RP2D dose being assigned to Part 2 participants. 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. Based on a review of available data, up to 36 additional participants may be randomized 2:1 to ATA188 or placebo. 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 first year will receive 2 cycles of ATA188 at the RP2D assigned at randomization 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 Q12M for up to 3 years (ie, Years 3 to 5) at the RP2D received in the double-blind period (Year 1 and Year 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).