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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03283826




Registration number
NCT03283826
Ethics application status
Date submitted
13/09/2017
Date registered
14/09/2017
Date last updated
16/06/2020

Titles & IDs
Public title
Phase 1 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis
Scientific title
A Phase 1, Two-part, Open-label Dose-escalation and Double-blind, Placebo-controlled Dose-expansion Study With an Open-label Extension to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis
Secondary ID [1] 0 0
ATA188-MS-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Progressive Multiple Sclerosis 0 0
Secondary Progressive Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - ATA188
Treatment: Drugs - Placebo

Experimental: ATA188 - Participants will receive ATA188 intravenously.

Placebo Comparator: Placebo - Participants will receive placebo matching to ATA188 intravenously.


Other interventions: ATA188
ATA188 is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ progressive multiple sclerosis.

Treatment: Drugs: Placebo
Placebo matching to ATA188

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1 and Part 2: Incidence of adverse events - Safety and tolerability
Timepoint [1] 0 0
At 12 months after the first dose of study drug
Primary outcome [2] 0 0
Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs
Timepoint [2] 0 0
At 12 months after the first dose of study drug
Primary outcome [3] 0 0
Part 1: Recommended Part 2 dose of ATA188 monotherapy - Dose assessment
Timepoint [3] 0 0
Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year)
Primary outcome [4] 0 0
Part 2: Change from baseline in immunoglobulin G (IgG) index, including quantification of IgG production - Antibody assessment and quantification
Timepoint [4] 0 0
At 12 months after the first dose of study drug
Secondary outcome [1] 0 0
Part 1: Change from baseline in expanded disability status scale (EDSS) score - Changes in disability score
Timepoint [1] 0 0
At 12 months after the first dose of study drug
Secondary outcome [2] 0 0
Part 2: Change from baseline in clinical disability as assessed by the EDSS score and/or Timed 25 foot Walk (T25W) and/or 9-hole Peg Test (9HPT) - Changes in disability score
Timepoint [2] 0 0
At 12 months after the first dose of study drug
Secondary outcome [3] 0 0
Part 2: Change from baseline in cervical spinal cord volume and whole brain volume on MRI scans - Change in MRI activity
Timepoint [3] 0 0
At 12 months after the first dose of study drug
Secondary outcome [4] 0 0
Part 2: Change from baseline in the number of Gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans - Change in MRI activity
Timepoint [4] 0 0
At 12 months after the first dose of study drug

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

- 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) ß, 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Griffith University, School of Medicine - Southport
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
4006 - Herston
Recruitment postcode(s) [3] 0 0
4222 - Southport
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Atara Biotherapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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]).
Trial website
https://clinicaltrials.gov/show/NCT03283826
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Kiren Kresa-Reahl, MD
Address 0 0
Atara Biotherapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Director
Address 0 0
Country 0 0
Phone 0 0
650-278-8930
Fax 0 0
Email 0 0
clinicalstudies@atarabio.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03283826