ULTIMATE 1
What it found
The main measure showed a statistically significant benefit.
| Measure | Estimate | 95% CI | p |
|---|---|---|---|
| Annualized Relapse Rate (ARR) | Rate Ratio (Ublituximab/Teriflunomide) 0.406 | 0.268–0.615 | <0.0001 |
Statistical analysis as posted on ClinicalTrials.gov.
What was tested
Treatment tested
- Ublituximab
B-lymphocyte antigen CD20 binding agent
Compared with
- Teriflunomide
Dihydroorotate dehydrogenase inhibitor
Placebo or sham
- Oral Placebo
- IV Placebo
Results by group
Annualized Relapse Rate (ARR)
Up to 96 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Ublituximab + Oral Placebo | 0.076 relapses per participant-years | 0.042–0.138 | 271 |
| Teriflunomide + IV Placebo | 0.188 relapses per participant-years | 0.124–0.283 | 274 |
Ublituximab + Oral Placebo
Teriflunomide + IV Placebo
p = <0.0001; Rate Ratio (Ublituximab/Teriflunomide) 0.406 (95% CI 0.268–0.615)
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Ublituximab + Oral Placebo | 273 | 31 (11.4%) | 2 |
| Teriflunomide + IV Placebo | 275 | 19 (6.9%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Annualized Relapse Rate (ARR)
Up to 96 weeks
RelapsesThe primary efficacy endpoint is ARR defined as the number of IRAP-confirmed relapsed per-subject year. The estimate of ARR for a treatment group will be the total number of relapses for subjects in the respective treatment group divided by the sum of treatment duration on study for subjects in that specific treatment group.
Relapses
Other measures (8)
Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant
Weeks 12, 24, 48, and 96
MRI lesionsTotal Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant
Weeks 24, 48, and 96
MRI lesionsTime to Confirmed Disability Progression (CDP) for at Least 12 Weeks
Up to Week 96
Disability progressionBladder, bowel and sexual functionPercentage of Participants With No Evidence of Disease Activity (NEDA)
Week 24 up to Week 96
Disability progressionRelapsesMRI lesionsPercentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)
Baseline up to Week 96
Thinking and memoryPercent Change From Baseline in Brain Volume
Baseline up to Week 96
Brain volume lossPercentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
From the first dose of study drug through the end of the study (up to approximately 116 weeks)
Safety1. Total number of gadolinium enhancing (Gd-enhancing) T1-lesions per MRI scan by Week 96.
MRI lesions
Who could take part
Relapsing MS · 18 to 55
Inclusion Criteria: * 18-55 age * Diagnosis of RMS (McDonald criteria 2010) * Active disease * Expanded disability status scale (EDSS) 0-5.5 (inclusive) at screening Exclusion Criteria: * Treatment with prior Anti-cluster of differentiate 20 (CD20) or other B cell directed treatment * Treatment with the following therapies at any time prior to randomization: alemtuzumab, natalizumab, teriflunomide, leflunomide and stem cell transplantation * Diagnosed with Primary Progressive MS (PPMS) * Pregnant or nursing
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
This study determines the Annualized Relapse Rate (ARR) in participants with RMS after 96 weeks (approximately 2 years) treatment with intravenous (IV) infusion of ublituximab/oral placebo compared to 14 mg oral teriflunomide/IV placebo.
Papers
Results
Disease outcomes with ublituximab in treatment-naïve participants: subpopulation analyses of the phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis.Front Immunol · 2026
Results
Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis.N Engl J Med · 2022
Results
A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.Mult Scler · 2021
Results
Hartung HP, Robertson D, Steinman L, Arnold DL, Qian P, Wray S, Fox E, Garner CA, Xu Y, Mok K, Gocke A, Cree BAC, Alvarez E. Efficacy of Ublituximab in People with Highly Active Relapsing Multiple Sclerosis. Neurol Ther. 2026 Jun;15(3):1081-1097. doi: 10.1007/s40120-026-00904-4. Epub 2026 Mar 6.Results
Alvarez E, Steinman L, Fox EJ, Hartung HP, Qian P, Wray S, Robertson D, Selmaj K, Wynn D, Mok K, Xu Y, Bodhinathan K, Miskin HP, Cree BAC. Improvements in no evidence of disease activity with ublituximab vs. teriflunomide in the ULTIMATE phase 3 studies in relapsing multiple sclerosis. Front Neurol. 2024 Oct 24;15:1473284. doi: 10.3389/fneur.2024.1473284. eCollection 2024.
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Linked trials
Extended by
TG1101-RMS303Phase 3 · Running, not recruiting
Links found where a registry record names another trial's registry number.
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History
Started
Sept 2017
Main results due
Jul 2020
Finished
Nov 2020
Results posted
Dec 2021
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