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NCT03277261: ULTIMATE 1

Study to Assess the Efficacy and Safety of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis (RMS) ( ULTIMATE 1 )

Completed Phase 3 Results posted Last updated 6 December 2021
What this trial tests

Phase 3 trial testing Ublituximab in Relapsing Multiple Sclerosis (RMS) in 549 participants. Completed in 6 November 2020.

Timeline
19 September 2017
Primary endpoint
23 July 2020
6 November 2020

Quick facts

Lead sponsorTG Therapeutics, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment549
Start date19 September 2017
Primary completion23 July 2020
Estimated completion6 November 2020
Sites14 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

TG Therapeutics, Inc. — full company profile →

Who can join

Adults 18 to 55, any sex, with Relapsing Multiple Sclerosis (RMS). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Annualized Relapse Rate (ARR) Primary · 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.

GroupValue95% CI
Ublituximab + Oral Placebo0.0760.042 – 0.138
Teriflunomide + IV Placebo0.1880.124 – 0.283
Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant Secondary · Weeks 12, 24, 48, and 96

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.

GroupValue95% CI
Ublituximab + Oral Placebo0.0160.008 – 0.032
Teriflunomide + IV Placebo0.4910.355 – 0.679
Total Number of New and Enlarging T2 Hyperintense Lesions (NELs) Per MRI Scan Per Participant Secondary · Weeks 24, 48, and 96

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.

GroupValue95% CI
Ublituximab + Oral Placebo0.2130.144 – 0.316
Teriflunomide + IV Placebo2.7892.136 – 3.643
Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks Secondary · Up to Week 96

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 abov

GroupValue95% CI
Ublituximab + Oral PlaceboNANA – NA
Teriflunomide + IV PlaceboNANA – NA
Percentage of Participants With No Evidence of Disease Activity (NEDA) Secondary · Week 24 up to Week 96

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.

GroupValue95% CI
Ublituximab + Oral Placebo44.6
Teriflunomide + IV Placebo15.0
Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT) Secondary · Baseline up to Week 96

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.

GroupValue95% CI
Ublituximab + Oral Placebo29.2
Teriflunomide + IV Placebo31.8
Percent Change From Baseline in Brain Volume Secondary · Baseline up to Week 96
GroupValue95% CI
Ublituximab + Oral Placebo-0.197-0.228 – -0.166
Teriflunomide + IV Placebo-0.125-0.155 – -0.095
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Secondary · From the first dose of study drug through the end of the study (up to approximately 116 weeks)

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 worse

TEAEs
GroupValue95% CI
Ublituximab + Oral Placebo86.1
Teriflunomide + IV Placebo89.1
TESAEs
GroupValue95% CI
Ublituximab + Oral Placebo11.4
Teriflunomide + IV Placebo6.9

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study drug through the end of the study (up to approximately 116 weeks). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ublituximab + Oral Placebo
Serious: 31/273 (11%)
Deaths: 2/274
Teriflunomide + IV Placebo
Serious: 19/275 (7%)
Deaths: 0/275

Serious adverse events (48 terms)

ReactionSystemUblituximab + Oral PlaceboTeriflunomide + IV Placebo
Neurological symptomNervous system disorders
PneumoniaInfections and infestations
COVID-19 pneumoniaInfections and infestations
Central nervous system enteroviral infectionInfections and infestations
Urinary tract infectionInfections and infestations
NeutropeniaBlood and lymphatic system disorders
HyperthyroidismEndocrine disorders
Pancreatitis chronicGastrointestinal disorders
Oesophageal achalasiaGastrointestinal disorders
AstheniaGeneral disorders
Anaphylactic reactionImmune system disorders
HypersensitivityImmune system disorders
AppendicitisInfections and infestations
Bullous erysipelasInfections and infestations
EncephalitisInfections and infestations
MeaslesInfections and infestations
Meningoencephalitis viralInfections and infestations
Peritonsillar abscessInfections and infestations
Pulmonary tuberculosisInfections and infestations
SalpingitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Bacterial infectionInfections and infestations
Lyme diseaseInfections and infestations
Pyelonephritis acuteInfections and infestations
ConcussionInjury, poisoning and procedural complications
Other adverse events (21 terms — click to expand)

ReactionSystemUblituximab + Oral PlaceboTeriflunomide + IV Placebo
HeadacheNervous system disorders
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
AlopeciaSkin and subcutaneous tissue disorders
Lymphocyte count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
LymphopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
HypertensionVascular disorders
Respiratory tract infection viralInfections and infestations
ChillsGeneral disorders
RhinitisInfections and infestations
Urinary tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations

Most-reported serious reactions: Neurological symptom, Pneumonia, COVID-19 pneumonia, Central nervous system enteroviral infection, Urinary tract infection, Neutropenia, Hyperthyroidism, Pancreatitis chronic.

Data from ClinicalTrials.gov NCT03277261 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Development of therapeutic antibodies for the treatment of diseases.
    Lu RM, Hwang YC, Liu IJ, Lee CC, et al · · 2020 · cited 1329× · PMID 31894001 · DOI 10.1186/s12929-019-0592-z
  2. B cell depletion therapies in autoimmune disease: advances and mechanistic insights.
    Lee DSW, Rojas OL, Gommerman JL. · · 2021 · cited 496× · PMID 33324003 · DOI 10.1038/s41573-020-00092-2
  3. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  4. Antibodies to watch in 2019.
    Kaplon H, Reichert JM. · · 2019 · cited 324× · PMID 30516432 · DOI 10.1080/19420862.2018.1556465
  5. Antibodies to watch in 2022.
    Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
  6. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  7. Antibodies to watch in 2023.
    Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
  8. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671

Verify or expand the search:

Other trials of Ublituximab

Trials testing the same drug.

Other recruiting trials for Relapsing Multiple Sclerosis (RMS)

Currently open trials in the same condition.

Other TG Therapeutics, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03277261.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing