Relapsing Multiple Sclerosis (RMS)Phase 3ULTIMATE 1NCT03277261
Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (RMS) ( ULTIMATE 1 )
A Phase 3 study testing Ublituximab and Teriflunomide in people with Relapsing Multiple Sclerosis (RMS), run by TG Therapeutics, Inc. at 14 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing Multiple Sclerosis (RMS)
- What is being tested?
- Ublituximab and Teriflunomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 549 participants
- Where
- 14 sitesUnited States
- Study dates
- 19 Sep 2017to 6 Nov 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 18-55 age
- Diagnosis of RMS (McDonald criteria 2010)
- Active disease
- Expanded disability status scale (EDSS) 0-5.5 (inclusive) at screening
Who cannot join
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
TG Therapeutics RMS Investigational Trial Site
Amherst, New York, 14226
TG Therapeutics RMS Investigational Trial Site
Carlsbad, California, 92001
TG Therapeutics RMS Investigational Trial Site
Dallas, Texas, 75246
TG Therapeutics RMS Investigational Trial Site
Detroit, Michigan, 48201
TG Therapeutics RMS Investigational Trial Site
Franklin, Tennessee, 37064
TG Therapeutics RMS Investigational Trial Site
Kansas City, Kansas, 66160
TG Therapeutics RMS Investigational Trial Site
Knoxville, Tennessee, 37922
TG Therapeutics RMS Investigational Trial Site
Long Beach, California, 90808
TG Therapeutics RMS Investigational Trial Site
Miami, Florida, 33136
TG Therapeutics RMS Investigational Trial Site
Northbrook, Illinois, 60062
TG Therapeutics RMS Investigational Trial Site
Pasadena, California, 91105
TG Therapeutics RMS Investigational Site
Round Rock, Texas, 78681
TG Therapeutics RMS Investigational Trial Site
Stanford, California, 94305
TG Therapeutics RMS Investigational Trial Site
Westerville, Ohio, 43081
About this study
Official title: Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE I STUDY)
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.
- Conditions
- Relapsing Multiple Sclerosis (RMS)
- Being tested
- Ublituximab, Teriflunomide, Oral Placebo, IV Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabBiological
Also called TG-1101
Administered as an IV infusion.
TeriflunomideDrug
Film-coated tablets administered orally.
Oral PlaceboDrug
Administered orally.
IV PlaceboDrug
Administered as an IV infusion.
| Study group | Role | What they receive |
|---|---|---|
| Ublituximab + Oral Placebo | Experimental | Participants were administered ublituximab 150 milligrams (mg), intravenous (IV) infusion over 4 hours (h) on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo once daily (QD) from Day 1 up to the last day of Week 95. Receives: Biological: Ublituximab; Drug: Oral Placebo |
| Teriflunomide + IV Placebo | Active comparator | Participants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72). Receives: Drug: Teriflunomide; Drug: IV Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Relapse Rate (ARR)
ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.
Measured: Up to 96 weeks
Secondary outcomes (7)
Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant
The total number of Gd-enhancing T1-lesions were calculated as the sum of the individual number of lesions at Weeks 12, 24, 48, and 96, divided by the total number of MRI scans of the brain.
Measured: Weeks 12, 24, 48, and 96
Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant
The total number of NELs were calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96, divided by the total number of MRI scans of the brain.
Measured: Weeks 24, 48, and 96
Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks
12-week CDP is defined as an increase in EDSS at least 1 point higher than the baseline EDSS if the baseline EDSS is ≤5.5 or at least 0.5 higher than the baseline EDSS if the baseline EDSS is >5.5. The EDSS is based on a standard neurological examination, (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) and ambulation function system assessments. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death) where higher scores indicate disability. The time to onset of 12-week CDP is the time to progression to the EDSS change defined above.
Measured: Up to Week 96
Percentage of Participants With No Evidence of Disease Activity (NEDA)
A participant with NEDA is defined as a participant without relapses confirmed by the IRAP, without MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12-week CDP. Any evidence of disease activity from Week 24 to Week 96 was counted as not reaching NEDA. Any evidence of disease activity before Week 24 was not counted.
Measured: Week 24 up to Week 96
Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)
The SDMT involves a simple substitution task using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses are done verbally. The administration time is approximately 5 minutes. The total SDMT score for each visit ranging from 0-110 is defined as the total number of correct answers reported in the case report form (CRF), where high scores indicate better outcome. Impaired SDMT is defined as a decrease from baseline of at least 4 points at any post-baseline assessment up to the Week 96 visit.
Measured: Baseline up to Week 96
Percent Change From Baseline in Brain Volume
Measured: Baseline up to Week 96
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A Serious AE is defined as any untoward medical occurrence that: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, and/or causes a congenital anomaly/birth defect. A TEAE is an AE that starts or worsens after receiving study drug.
Measured: From the first dose of study drug through the end of the study (up to approximately 116 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start19 Sep 2017
- Primary completion23 Jul 2020
- Study completion6 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Relapsing Multiple Sclerosis (RMS)Studies of the same condition, open and under way.
- More trials run by TG Therapeutics, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, multi-center, double-blinded, active-controlled study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 549 participants (actual)
Sponsor and investigators
- Lead sponsor
- TG Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03277261
- Sponsor's protocol ID
- TG1101-RMS301
- Other IDs
- 2017-000638-75, 2017
- Acronym
- ULTIMATE 1
- Status last verified
- Nov 2021
- First submitted
- 7 Sep 2017
- Last updated
- 6 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data will be shared after study completion via publication.
Publications
Robertson D, Alvarez E, Steinman L, Hartung HP, Qian P, Selmaj K, Wray S, Wynn D, Fox EJ, Mok K, Miskin HP, Xu Y, Garner CA, Cree BAC. Disease outcomes with ublituximab in treatment-naive participants: subpopulation analyses of the phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis. Front Immunol. 2026 May 29;17:1771848. doi: 10.3389/fimmu.2026.1771848. eCollection 2026.
PubMed 42292352Hartung 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.
PubMed 41787239Alvarez 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.
PubMed 39512280Steinman L, Fox E, Hartung HP, Alvarez E, Qian P, Wray S, Robertson D, Huang D, Selmaj K, Wynn D, Cutter G, Mok K, Hsu Y, Xu Y, Weiss MS, Bosco JA, Power SA, Lee L, Miskin HP, Cree BAC; ULTIMATE I and ULTIMATE II Investigators. Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2022 Aug 25;387(8):704-714. doi: 10.1056/NEJMoa2201904.
PubMed 36001711
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE I STUDY)
- ClinicalTrials.gov ID
- NCT03277261
- Acronym / sponsor ID
- ULTIMATE 1 / TG1101-RMS301
- Conditions
- Relapsing Multiple Sclerosis (RMS)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 549 participants (actual)
- Lead sponsor
- TG Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 19 Sep 2017 (actual)
- Primary completion
- 23 Jul 2020 (actual)
- Study completion
- 6 Nov 2020 (actual)
- First posted
- 11 Sep 2017 (actual)
- Results
- Posted 6 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, multi-center, double-blinded, active-controlled study
| Arm | Type | Receives |
|---|---|---|
| Ublituximab + Oral Placebo | Experimental | Biological: Ublituximab, Drug: Oral PlaceboParticipants were administered ublituximab 150 milligrams (mg), intravenous (IV) infusion over 4 hours (h) on Day 1 followed by 450 mg over 1 h on Days 15, 168, 336 and 504 (Week 72) along with the oral placebo once daily (QD) from Day 1 up to the last day of Week 95. |
| Teriflunomide + IV Placebo | Active comparator | Drug: Teriflunomide, Drug: IV PlaceboParticipants were administered teriflunomide 14 mg tablet, orally, QD from Day 1 up to the last day of Week 95 along with the placebo IV infusion on Days 1, 15, 168, 336 and 504 (Week 72). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 18-55 age
- Diagnosis of RMS (McDonald criteria 2010)
- Active disease
- Expanded disability status scale (EDSS) 0-5.5 (inclusive) at screening
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UblituximabAlso: TG-1101Administered as an IV infusion. | Biological | Ublituximab + Oral Placebo |
| TeriflunomideFilm-coated tablets administered orally. | Drug | Teriflunomide + IV Placebo |
| Oral PlaceboAdministered orally. | Drug | Ublituximab + Oral Placebo |
| IV PlaceboAdministered as an IV infusion. | Drug | Teriflunomide + IV Placebo |
Primary outcome
Annualized Relapse Rate (ARR)
Time frame: Up to 96 weeks
ARR is defined as the number of Independent Relapse Adjudication Panel (IRAP)-confirmed relapses per participant year. The estimate of ARR for a treatment group is the total number of relapses for participants in the respective treatment group divided by the sum of treatment duration for participants in that specific treatment group.
7 secondary outcomes
Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant
Time frame: Weeks 12, 24, 48, and 96
Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant
Time frame: Weeks 24, 48, and 96
Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks
Time frame: Up to Week 96
Percentage of Participants With No Evidence of Disease Activity (NEDA)
Time frame: Week 24 up to Week 96
Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)
Time frame: Baseline up to Week 96
Percent Change From Baseline in Brain Volume
Time frame: Baseline up to Week 96
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From the first dose of study drug through the end of the study (up to approximately 116 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42292352Robertson D, Alvarez E, Steinman L, Hartung HP, Qian P, Selmaj K, Wray S, Wynn D, Fox EJ, Mok K, Miskin HP, Xu Y, Garner CA, Cree BAC. Disease outcomes with ublituximab in treatment-naive participants: subpopulation analyses of the phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis. Front Immunol. 2026 May 29;17:1771848. doi: 10.3389/fimmu.2026.1771848. eCollection 2026.
- Derived from this study: PubMed 41787239Hartung 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.
- Derived from this study: PubMed 39512280Alvarez 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.
- Derived from this study: PubMed 36001711Steinman L, Fox E, Hartung HP, Alvarez E, Qian P, Wray S, Robertson D, Huang D, Selmaj K, Wynn D, Cutter G, Mok K, Hsu Y, Xu Y, Weiss MS, Bosco JA, Power SA, Lee L, Miskin HP, Cree BAC; ULTIMATE I and ULTIMATE II Investigators. Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2022 Aug 25;387(8):704-714. doi: 10.1056/NEJMoa2201904.
- Individual participant dataSharing planned: Undecided. Data will be shared after study completion via publication.
Related trials for Relapsing Multiple Sclerosis (RMS)
Active, not recruitingPhase 3
An Extension Study of Ublituximab in Participants With Relapsing Multiple Sclerosis
Relapsing Multiple Sclerosis (RMS)
RecruitingObservational study
A Study Evaluating the Real World Experience of Participants Treated With BRIUMVI® (Ublituximab-xiiy) for Relapsing Multiple Sclerosis (RMS)
Relapsing Multiple Sclerosis, Multiple Sclerosis
RecruitingPhase 2/3
Study to Assess Effects of Ublituximab in Pediatric Participants With Relapsing Forms of Multiple Sclerosis
Relapsing Multiple Sclerosis
Active, not recruitingObservational study
Early Versus Late Ofatumumab (Kesimpta®) Use in Austrian RMS-Patients Over 2 Years
Relapsing Multiple Sclerosis
RecruitingPhase 3
Efficacy and Safety of Remibrutinib After Switching From Ocrelizumab in Participants Living With Relapsing Multiple Sclerosis.
Relapsing Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ublituximab and Teriflunomide in people with Relapsing Multiple Sclerosis (RMS), run by TG Therapeutics, Inc. at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Relapse Rate (ARR) (time frame: Up to 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03277261, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2021.