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

November 11, 2021 updated by: TG Therapeutics, Inc.

Phase III: UbLiTuximab in Multiple Sclerosis Treatment Effects (ULTIMATE II 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

545

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 58018
        • TG Therapeutics RMS Investigational Trial Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • TG Therapeutics RMS Investigational Trial Site
    • Florida
      • Tampa, Florida, United States, 33612
        • TG Therapeutics RMS Investigational Trial Site
    • Kentucky
      • Lexington, Kentucky, United States, 40513
        • TG Therapeutics RMS Investigational Trial Site
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • TG Therapeutics RMS Investigational Trial Site
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • TG Therapeutics RMS Investigational Trial Site
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • TG Therapeutics RMS Investigational Trial Site
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • TG Therapeutics RMS Investigational Trial Site
    • New York
      • Patchogue, New York, United States, 11772
        • TG Therapeutics RMS Investigational Trial Site
    • Ohio
      • Columbus, Ohio, United States, 43221
        • TG Therapeutics RMS Investigational Trial Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • TG Therapeutics RMS Investigational Trial Site
    • Texas
      • San Antonio, Texas, United States, 78258
        • TG Therapeutics RMS Investigational Trial Site
    • Washington
      • Seattle, Washington, United States, 98122
        • TG Therapeutics RMS Investigational Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of relapsing multiple sclerosis (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 multiple sclerosis (PPMS)
  • Pregnant or nursing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ublituximab + Oral Placebo
Participants received ublituximab intravenous (IV) infusion, 150 milligrams (mg) 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 tablet, once daily (QD) from Day 1 up to the last day of Week 95.
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
Drug: Oral Placebo
Administered orally.
Active Comparator: Teriflunomide + IV Placebo
Participants received 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).
Drug: Teriflunomide
Film coated tablets administered orally.
Drug: IV Placebo
Administered as an IV Infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Relapse Rate (ARR)
Time Frame: Up to 96 weeks
ARR is defined as the number of Independent Relapse Adjudication Committee (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.
Up to 96 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Number of Gadolinium (Gd)-Enhancing T1-Lesions Per Magnetic Resonance Imaging (MRI) Scan Per Participant
Time Frame: 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.
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
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.
Weeks 24, 48, and 96
Time to Confirmed Disability Progression (CDP) for at Least 12 Weeks
Time Frame: 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 above.
Up to Week 96
Percentage of Participants With No Evidence of Disease Activity (NEDA)
Time Frame: From Week 24 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.
From Week 24 to Week 96
Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT)
Time Frame: Baseline 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 of at least 4 points from baseline at any post-baseline assessment up to the Week 96 visit.
Baseline to Week 96
Percent Change From Baseline in Brain Volume
Time Frame: Baseline to Week 96
Baseline 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)
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. TEAEs are AEs that start or worsen after receiving the study drug.
From the first dose of study drug through the end of the study (up to approximately 116 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TG Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 25, 2017

Primary Completion (Actual)

August 4, 2020

Study Completion (Actual)

November 12, 2020

Study Registration Dates

First Submitted

September 7, 2017

First Submitted That Met QC Criteria

September 7, 2017

First Posted (Actual)

September 11, 2017

Study Record Updates

Last Update Posted (Actual)

December 6, 2021

Last Update Submitted That Met QC Criteria

November 11, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TG1101-RMS302
  • 2017-000639-15 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Data will be shared after study completion via publication.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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