Multiple SclerosisPhase 2NCT02738775
Phase IIa Study of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis
A Phase 2 study testing Ublituximab in people with Multiple Sclerosis, run by TG Therapeutics, Inc. at 12 sites in United States.
Trial summary
This study evaluates the use of single agent ublituximab, a novel monoclonal antibody, in participants with relapsing forms of multiple sclerosis. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ublituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 12 sitesUnited States
- Study dates
- 27 May 2016to 13 Aug 2018
- Phase
- Phase 2
- 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
- Diagnosis of relapsing multiple sclerosis
- Active disease
- Greater than or equal to (≥) 2 relapses in prior 2 years or 1 relapse in the year prior to screening and/or ≥1 gadolinium (Gd) enhancing lesion
Who cannot join
- Treatment with anti-cluster of differentiation 20 (CD20) monoclonal antibody within the last 12 months
- Treatment with alemtuzumab within the last 12 months
- Pregnant or nursing mothers
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
TG Therapeutics Investigational Trial Site
Akron, Ohio, 44320
TG Therapeutics Investigational Trial Site
Aurora, Colorado, 80045
TG Therapeutics Investigational Trial Site
Columbus, Ohio, 43201
TG Therapeutics Investigational Trial Site
Fort Collins, Colorado, 80528
TG Therapeutics Investigational Trial Site
Knoxville, Tennessee, 37922
TG Therapeutics Investigational Trial Site
Lexington, Kentucky, 40509
TG Therapeutics Investigational Trial Site
Pasadena, California, 91105
TG Therapeutics Investigational Trial Site
Phoenix, Arizona, 85018
TG Therapeutics Investigational Trial Site
Round Rock, Texas, 78681
TG Therapeutics Investigational Trial Site
San Antonio, Texas, 78258
TG Therapeutics Investigational Trial Site
Teaneck, New Jersey, 07666
TG Therapeutics Investigational Trial Site
Torrance, California, 90502
About this study
Official title: A Placebo-Controlled Multi-Center Phase IIa Dose Finding Study of Ublituximab, a Third-Generation Anti-CD20 Monoclonal Antibody, in Patients With Relapsing Forms of Multiple Sclerosis.
This study evaluates the use of single agent ublituximab, a novel monoclonal antibody, in participants with relapsing forms of multiple sclerosis.
- Conditions
- Multiple Sclerosis
- Being tested
- Ublituximab, Placebo
- Keywords
- multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
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.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Participant received intravenous (IV) infusion of ublituximab 150 milligrams (mg)/4 hour (hr) on Day 1, 450 mg/3 hr on Day 15 and 450 mg/1.5 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /3 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
| Cohort 2 | Experimental | Participant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1.5 hr on Day 15 and 450 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1.5 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
| Cohort 3 | Experimental | Participant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
| Cohort 4 | Experimental | Participant received IV infusion of ublituximab 150 mg/3 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /3 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
| Cohort 5 | Experimental | Participant received IV infusion of ublituximab 150 mg/2 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /2 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
| Cohort 6 | Experimental | Participant received IV infusion of ublituximab 150 mg/1 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /1 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. Receives: Biological: Ublituximab; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Responder Rate of B-Cell Depletion at Week 4
Responders Rate is defined as percentage of participants with greater than or equal to (≥) 95% reduction of B cells (cluster of differentiation 19 positive [CD19+] cells) within 2 weeks after the second infusion (Day 15).
Measured: Week 4
Secondary outcomes (12)
Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48
The Gd-enhancing T1 lesions were evaluated using magnetic resonance imaging (MRI) technique.
Measured: Weeks 24 and 48
Number of New or Enlarging T2 Lesions at Weeks 24 and 48
The new or enlarging T2 lesions were evaluated using MRI technique.
Measured: Weeks 24 and 48
Annualized Relapse Rate (ARR)
ARR at Week 48 is calculated as the ratio of the sum of all participants confirmed relapse counts divided by the sum of all participants treatment duration (in years).
Measured: Week 48
Relapse Rate Reduction (RRR)
RRR was calculated as the percentage reduction from baseline ARR to ARR at Week 48.
Measured: Baseline to Week 48
Percentage of Relapse Free Participants
Participant was considered as free of clinical relapse if participant had no confirmed clinical relapse before treatment discontinuation/until end of Week 48. Relapses are defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS), and immediately preceded by a stable or improving neurological state of at least 30 days.
Measured: Week 48
Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells
Cluster of Differentiation (CD)19 is a marker of B cells, the protein has been used to diagnose cancers that arise from this type of cell - notably B cell lymphomas, acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). The majority of B cell malignancies express normal to high levels of CD19. Memory B cell is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. A naive B cell is a B cell that has not been exposed to an antigen. Once exposed to an antigen, the naive B cell either becomes a memory B cell or a plasma cell that secretes antibodies specific to the antigen that was originally bound.
Measured: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 plus 2 days, Weeks 25, 28, 36, 40, 44 and 48
Change From Baseline in Sustained B Cell
Sustained B cell reduction is defined as B-cell reductions achieved on pre-dose at Week 24 and Week 48.
Measured: Baseline to pre-dose at Week 24 and Week 48
Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive)
A blood sample was collected and was sent to the laboratory for analysis of CD4+.
Measured: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive)
A blood sample was collected and was sent to the laboratory for analysis of CD8+.
Measured: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Additional Immune Profiling-Interleukin 10 (IL10)
A blood sample was collected and was sent to the laboratory for analysis of IL-10. IL-10 is an anti-inflammatory cytokine that maintains the balance of the immune response, allowing the clearance of infection while minimizing damage to the host.
Measured: Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48
Additional Immune Profiling-Natural Killer (NK) Cells
A blood sample was collected and was sent to the laboratory for analysis of NK cells. Percentage of NK cells per ml of blood. NK cells are lymphocytes with the ability to kill tumor cells without deliberate immunization or activation.
Measured: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Pharmacokinetic Parameter: Plasma Concentration of Ublituximab
Plasma concentration is defined as the measured concentration of ublituximab.
Measured: Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2016 (estimated)
- Study start27 May 2016
- Primary completion27 Sep 2017
- Study completion13 Aug 2018
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.
- Other trials for Multiple SclerosisStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- TG Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edward Fox, MD, PhD, Study chair, Central Texas Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02738775
- Sponsor's protocol ID
- TG1101-RMS-201
- Status last verified
- Jun 2021
- First submitted
- 10 Apr 2016
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Data will be shared after study completion via publication
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled Multi-Center Phase IIa Dose Finding Study of Ublituximab, a Third-Generation Anti-CD20 Monoclonal Antibody, in Patients With Relapsing Forms of Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT02738775
- Acronym / sponsor ID
- TG1101-RMS-201
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- TG Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 May 2016 (actual)
- Primary completion
- 27 Sep 2017 (actual)
- Study completion
- 13 Aug 2018 (actual)
- First posted
- 14 Apr 2016 (estimated)
- Results
- Posted 15 Jul 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 evaluates the use of single agent ublituximab, a novel monoclonal antibody, in participants with relapsing forms of multiple sclerosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received intravenous (IV) infusion of ublituximab 150 milligrams (mg)/4 hour (hr) on Day 1, 450 mg/3 hr on Day 15 and 450 mg/1.5 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /3 hr on Day 15 before receiving ublituximab. |
| Cohort 2 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1.5 hr on Day 15 and 450 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1.5 hr on Day 15 before receiving ublituximab. |
| Cohort 3 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. |
| Cohort 4 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received IV infusion of ublituximab 150 mg/3 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /3 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. |
| Cohort 5 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received IV infusion of ublituximab 150 mg/2 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /2 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. |
| Cohort 6 | Experimental | Biological: Ublituximab, Drug: PlaceboParticipant received IV infusion of ublituximab 150 mg/1 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /1 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Diagnosis of relapsing multiple sclerosis
- Active disease
- Greater than or equal to (≥) 2 relapses in prior 2 years or 1 relapse in the year prior to screening and/or ≥1 gadolinium (Gd) enhancing lesion
Key exclusion criteria (3 listed)
- Treatment with anti-cluster of differentiation 20 (CD20) monoclonal antibody within the last 12 months
- Treatment with alemtuzumab within the last 12 months
- Pregnant or nursing mothers
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 | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
| Placebo | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5, Cohort 6 |
Primary outcome
Responder Rate of B-Cell Depletion at Week 4
Time frame: Week 4
Responders Rate is defined as percentage of participants with greater than or equal to (≥) 95% reduction of B cells (cluster of differentiation 19 positive [CD19+] cells) within 2 weeks after the second infusion (Day 15).
12 secondary outcomes
Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48
Time frame: Weeks 24 and 48
Number of New or Enlarging T2 Lesions at Weeks 24 and 48
Time frame: Weeks 24 and 48
Annualized Relapse Rate (ARR)
Time frame: Week 48
Relapse Rate Reduction (RRR)
Time frame: Baseline to Week 48
Percentage of Relapse Free Participants
Time frame: Week 48
Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells
Time frame: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 plus 2 days, Weeks 25, 28, 36, 40, 44 and 48
Change From Baseline in Sustained B Cell
Time frame: Baseline to pre-dose at Week 24 and Week 48
Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive)
Time frame: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive)
Time frame: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Additional Immune Profiling-Interleukin 10 (IL10)
Time frame: Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48
Additional Immune Profiling-Natural Killer (NK) Cells
Time frame: Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48
Pharmacokinetic Parameter: Plasma Concentration of Ublituximab
Time frame: Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Data will be shared after study completion via publication
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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.
Edward Fox, MD, PhD study chair
Central Texas Neurology
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ublituximab in people with Multiple Sclerosis, run by TG Therapeutics, Inc. at 12 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 3 inclusion and 3 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 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Jul 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?
Responder Rate of B-Cell Depletion at Week 4 (time frame: Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2021.