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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03277261
Recruitment Status : Completed
First Posted : September 11, 2017
Results First Posted : December 6, 2021
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
TG Therapeutics, Inc.

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis (RMS) Biological: Ublituximab Drug: Teriflunomide Drug: Oral Placebo Drug: IV Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 549 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, multi-center, double-blinded, active-controlled study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blinded, active-controlled study
Primary Purpose: Treatment
Official Title: Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE I STUDY)
Actual Study Start Date : September 19, 2017
Actual Primary Completion Date : July 23, 2020
Actual Study Completion Date : November 6, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Ublituximab + Oral Placebo
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.
 Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

Drug: Oral Placebo
Administered orally.
Active Comparator: Teriflunomide + IV Placebo
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).
 Drug: Teriflunomide
Film-coated tablets administered orally.

Drug: IV Placebo
Administered as an IV infusion.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Percentage of Participants With No Evidence of Disease Activity (NEDA) [ Time Frame: 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.

  5. Percentage of Participants With Impaired Symbol Digit Modalities Test (SDMT) [ Time Frame: 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.

  6. Percent Change From Baseline in Brain Volume [ Time Frame: Baseline up to Week 96 ]
  7. 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. A TEAE is an AE that starts or worsens after receiving study drug.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277261


Locations
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United States, California
TG Therapeutics RMS Investigational Trial Site
Carlsbad, California, United States, 92001
TG Therapeutics RMS Investigational Trial Site
Long Beach, California, United States, 90808
TG Therapeutics RMS Investigational Trial Site
Pasadena, California, United States, 91105
TG Therapeutics RMS Investigational Trial Site
Stanford, California, United States, 94305
United States, Florida
TG Therapeutics RMS Investigational Trial Site
Miami, Florida, United States, 33136
United States, Illinois
TG Therapeutics RMS Investigational Trial Site
Northbrook, Illinois, United States, 60062
United States, Kansas
TG Therapeutics RMS Investigational Trial Site
Kansas City, Kansas, United States, 66160
United States, Michigan
TG Therapeutics RMS Investigational Trial Site
Detroit, Michigan, United States, 48201
United States, New York
TG Therapeutics RMS Investigational Trial Site
Amherst, New York, United States, 14226
United States, Ohio
TG Therapeutics RMS Investigational Trial Site
Westerville, Ohio, United States, 43081
United States, Tennessee
TG Therapeutics RMS Investigational Trial Site
Franklin, Tennessee, United States, 37064
TG Therapeutics RMS Investigational Trial Site
Knoxville, Tennessee, United States, 37922
United States, Texas
TG Therapeutics RMS Investigational Trial Site
Dallas, Texas, United States, 75246
TG Therapeutics RMS Investigational Site
Round Rock, Texas, United States, 78681
Sponsors and Collaborators
TG Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by TG Therapeutics, Inc.:
Study Protocol  [PDF] September 4, 2020
Statistical Analysis Plan  [PDF] September 4, 2020

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: TG Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03277261    
Other Study ID Numbers: TG1101-RMS301
2017-000638-75 ( EudraCT Number )
First Posted: September 11, 2017    Key Record Dates
Results First Posted: December 6, 2021
Last Update Posted: December 6, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data will be shared after study completion via publication.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Teriflunomide
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors