Phase 1 Study to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03283826|
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : April 15, 2020
|Condition or disease||Intervention/treatment||Phase|
|Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis||Biological: ATA188 Drug: Placebo||Phase 1|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||97 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||Double (Participant, Investigator)|
|Official 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|
|Actual Study Start Date :||October 19, 2017|
|Estimated Primary Completion Date :||September 2022|
|Estimated Study Completion Date :||February 2026|
Participants will receive ATA188 intravenously.
ATA188 is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ progressive multiple sclerosis.
Placebo Comparator: Placebo
Participants will receive placebo matching to ATA188 intravenously.
Placebo matching to ATA188
- Part 1 and Part 2: Incidence of adverse events [ Time Frame: At 12 months after the first dose of study drug ]Safety and tolerability
- Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs [ Time Frame: At 12 months after the first dose of study drug ]
- Part 1: Recommended Part 2 dose of ATA188 monotherapy [ Time Frame: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year) ]Dose assessment
- Part 2: Change from baseline in immunoglobulin G (IgG) index, including quantification of IgG production [ Time Frame: At 12 months after the first dose of study drug ]Antibody assessment and quantification
- Part 1: Change from baseline in expanded disability status scale (EDSS) score [ Time Frame: At 12 months after the first dose of study drug ]Changes in disability score
- 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) [ Time Frame: At 12 months after the first dose of study drug ]Changes in disability score
- Part 2: Change from baseline in cervical spinal cord volume and whole brain volume on MRI scans [ Time Frame: At 12 months after the first dose of study drug ]Change in MRI activity
- Part 2: Change from baseline in the number of Gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans [ Time Frame: At 12 months after the first dose of study drug ]Change in MRI activity
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03283826
|Contact: Study Directoremail@example.com|
|United States, Arizona|
|Scottsdale, Arizona, United States, 85259-5452|
|United States, Louisiana|
|The NeuroMedical Center Clinic, PC||Withdrawn|
|Baton Rouge, Louisiana, United States, 70810-1685|
|Ochsner Clinic Foundation||Recruiting|
|New Orleans, Louisiana, United States, 70121|
|Contact: Bridget Bagert, MD 504-703-7458 firstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104-5127|
|Contact: Amit Bar-Or, MD, FRCP, FAAN, FANA 215-220-9384 email@example.com|
|United States, Tennessee|
|Advanced Neurosciences Institute ANI - Franklin||Recruiting|
|Franklin, Tennessee, United States, 37064|
|Contact: Samue Hunter 615-595-0265 SFHUNTER@NEUROSCI.US|
|United States, Texas|
|The University of Texas Health Science Center at Houston||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: John Lindsey, MD 832-325-7082 firstname.lastname@example.org|
|Australia, New South Wales|
|Liverpool, New South Wales, Australia, 2170|
|Contact: Suzanne Hodgkinson, BSc, MB, BSFRACP, PhD +61(2) 96164689 email@example.com|
|Royal Brisbane and Women's Hospital||Recruiting|
|Brisbane, Queensland, Australia, 4029|
|Contact: Michael Pender, MD, PhD, FRACP, MBBS +61 (7) 3365 5132 firstname.lastname@example.org|
|Griffith University, School of Medicine||Recruiting|
|Southport, Queensland, Australia, 4222|
|Contact: Simon J Broadley, BSc, MBChB, PhD, FRACP +61 (7) 567 80174 email@example.com|
|Study Director:||Kiren Kresa-Reahl, MD||Atara Biotherapeutics|