UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE II)
Research type
Research Study
Full title
Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE II STUDY)
IRAS ID
225521
Contact name
Francisco Javier Carod Artal
Contact email
Sponsor organisation
TG Therapeutics
Eudract number
2017-000639-15
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Summary of Research
This is a 120 week, phase 3, randomised, multi-centre, double-blinded study that is primarily designed to test the efficacy and safety of ublituximab in Relapsing (a recurrence of symptoms of a disease after a period of improvement) forms of Multiple Sclerosis (RMS), in comparison to teriflunomide, an orally administered pyrimidine synthesis inhibitor currently approved for the treatment of RMS. The goal is to demonstrate that ublituximab is a safe and effective treatment that will markedly improve health outcomes in those living with RMS.The study may involve 25 visits or more to the study site or facility for up to 120 weeks. The time the participants spend in the study will depend on how long they continue to receive study treatment. Approximately 440 men and women with RMS, between the ages of 18 and 55, inclusive, may participate in this study.
The participants will be screened up to 4 weeks before first dosing date and the qualified participants will be randomised in a [1:1] ratio to one of two treatment cohorts to receive either ublituximab 150mg on Week 1 Day 1, 450mg on Week 3 Day 15, and Weeks 24, 48, and 72 or teriflunomide (14 mg, once a day). There will be two treatment cohorts (approximately 220 participants treated with teriflunomide and approximately 220 participants treated with ublituximab). The participants within each cohort will receive either active treatment ublituximab infusion/Placebo or teriflunomide tablets/Placebo.
The participants will be treated for 96 weeks and followed by 20 weeks follow-up period after the last trial treatment.
An independent DSMB will be established to advise the sponsor on safety and ethical issues of the study.
The study is sponsored by TG Therapeutics Inc.
Summary of Results
Lay summary of study results: The ULTIMATE II Study (UbLiTuximab In Multiple Sclerosis Treatment Effects II) was a phase III study designed to assess the Annualized Relapse Rate (ARR) and safety/tolerability of ublituximab (an anti-CD20 monoclonal antibody) compared to teriflunomide in participants with relapsing forms of Multiple Sclerosis (RMS). Eligible participants were randomly assigned in a 1:1 ratio to treatment with ublituximab/oral placebo or teriflunomide/IV placebo. Participants were men and women with RMS aged ≥18 and ≤55 years. 545 participants were enrolled and randomized. The maximum study duration for each participant was 120 weeks, including a 4-week Screening Period, a 96-week Treatment Period, and a 20-week Follow-up Period. The study was conducted at 50 study centers in 8 countries in Europe and North America from 25 Aug 2017 to 12 Nov 2020. Ublituximab notably reduced ARR, the primary endpoint, defined as the number of confirmed relapses per participant year. The treatment effect of ublituximab versus teriflunomide was statistically significant in favor of ublituximab In addition, ublituximab demonstrated robust efficacy on magnetic resonance imaging (MRI) parameters. For safety and tolerability, ublituximab treatment was consistent with anti-CD20+ monoclonal antibody effects and/or expected changes for patients with RMS. The proportion of participants who had any treatment-emergent adverse event (TEAE) was similar in both treatment groups. The most frequently reported TEAEs (≥10% in both treatment groups) were headache, nasopharyngitis, respiratory tract infection, and nausea, occurring in 103 (37.9%), 66 (24.3%), 30 (11.0%), and 29 (10.7%) participants, respectively, in the ublituximab group and 87 (31.9%), 54 (19.8%), 28 (10.3%), and 28 (10.3%) participants, respectively, in the teriflunomide group.REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
17/NW/0574
Date of REC Opinion
4 Dec 2017
REC opinion
Further Information Favourable Opinion