Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ublituximab · 15 trials · 16 indications
The Gd-enhancing T1 lesions will be evaluated using magnetic resonance imaging (MRI) technique.
ARR is defined as the number of relapses per-participant year. The estimate of ARR will be the total number of relapses divided by the sum of duration on study treatment (years).
ORR: Percentage of participants with best overall response of partial response(PR) and complete response(CR). CR criteria: No evidence of new disease; Absolute lymphocyte count(ALC)\<4x10\^9/liter(L); Regression of all target nodal masses to ≤1.5 centimeters(cm) in longest diameter(LD); Normal spleen,liver size; Regression to normal of all nodal non-target disease and disappearance of all detectable; Non-nodal, non-target disease; Morphologically negative bone marrow; No lymphoid nodules; Absolute neutrophil count(ANC)\>1.5x10\^9/L,platelets≥100x10\^9/L,hemoglobin (Hgb)≥110 gram per liter(g/L). PR criteria: No evidence of new disease; Response in 2 of following if abnormal at baseline: ALC\<4x10\^9/L or \>=50% decrease from baseline in sum of products(SPD) of target nodal lesions; splenomegaly; hepatomegaly;\>=50% decrease from baseline in CLL marrow infiltrate/B-lymphoid nodules; response in any 1:ANC\>1.5x10\^9/L,platelets\>100x10\^9/L,Hgb\>110g/L or \>=50% increase over baseline in any of these.
to determine the incidence of adverse events and any abnormal laboratory values
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).
To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities
To determine the incidence of adverse events, any potential abnormal laboratory results and any dose-limiting toxicities
Safety for all study patients will be evaluated by a Data Safety Monitoring Board to determine if feasible to continue with dose escalation
| Arm | Type | Description |
|---|---|---|
| Ublituximab IV | ACTIVE_COMPARATOR | Approved dosage. |
| Ublituximab SC Regimen 1 | EXPERIMENTAL | New regimen. |
| Ublituximab SC Regimen 2 | EXPERIMENTAL | New regimen. |
| Part A: Ublituximab | EXPERIMENTAL | Participants will receive a modified regimen of ublituximab including infusions on Day 1 of Week 1 (W1D1), Day 15, if applicable, and ublituximab 450 milligrams (mg) infusion at Week 24. With Protocol Version 6.0, enrollment in Part A was closed. |
| Part B: Ublituximab /Placebo (Treatment Arm A) | EXPERIMENTAL | Participants will receive 600 mg of ublituximab on W1D1 followed by a placebo infusion on Day 15 and 450 mg ublituximab infusion at Week 24. With Protocol Version 7.0, enrollment in Part B will be closed. |
| Part B: Ublituximab (Treatment Arm B) | EXPERIMENTAL | Participants will receive 150 mg of ublituximab on W1D1 followed by 450 mg on Day 15 and at Week 24. With Protocol Version 7.0, enrollment in Part B will be closed. |
| Part C: Ublituximab (Treatment Arm C) | EXPERIMENTAL | Participants will receive 150 mg of ublituximab on W1D1, followed by 450 mg on Day 15 and at Week 24. |
| Ublituximab Infusions | EXPERIMENTAL | RMS301/RMS302: All participants transferring from RMS301/RMS302 who sign consent for this study will receive an initial 4-hour infusion of 150 mg ublituximab on Week 1 (Day 1) followed by a 1-hour infusion of 450 mg ublituximab 14 days later Week 3 (Day 15). Subsequent infusions of ublituximab will be administered at 450 mg for 1-hour every 24 weeks from Weeks 24 to 312. RMS201E: All participants transferring from RMS201E who sign consent for this study will receive a 1-hour infusion of 450 mg ublituximab on Week 1 (Day 1) and subsequent infusions of ublituximab will be administered at 450 mg for 1-hour every 24 weeks from Weeks 24 to 312. For all participants (RMS301/RMS302/RMS201E), infusion treatment will continue for 312 weeks, or until physician or participant decision to withdraw from the study. |
| 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. |
| 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). |
| Ublituximab + Ibrutinib | EXPERIMENTAL | Participants will receive ublituximab intravenous (IV) infusion, up to 150 milligrams (mg) once on Day 1, 750 mg on Day 2, 900 mg on Days 8 and 15 of Cycle 1 (Cycle duration=28 days) followed by 900 mg on Day 1 of Cycles 2 to 6 and 900 mg on Day 1 of every 3rd cycle thereafter for up to 62 months along with ibrutinib 420 mg capsules, orally, once daily (QD) in each 28-day cycle for up to 62 months. |
| Ibrutinib | ACTIVE_COMPARATOR | Participants will receive ibrutinib 420 mg capsules, orally, QD in each 28-day cycle up to 62 months. |
| Randomized controlled period (RCP) | EXPERIMENTAL | Responder participants from efgartigimod induction period will be randomised 1:1 ratio to receive either ublituximab or ublituximab matching-placebo intravenous (IV) infusion. |
| Open-label period (OLP): Ublituximab | EXPERIMENTAL | Non-responder participants from efgartigimod induction period will receive ublituximab IV infusion. |
| Ublituximab | EXPERIMENTAL | Participants will receive ublituximab intravenous (IV) infusion. |
| Part B: Ublituximab | EXPERIMENTAL | New Regimen |
| Part B: Placebo | PLACEBO_COMPARATOR | - |
| Part B: Fingolimod | EXPERIMENTAL | - |
| Part B: IV Placebo | PLACEBO_COMPARATOR | - |
| Part C: OLE | EXPERIMENTAL | - |
| Part 1: Ublituximab SC | EXPERIMENTAL | Participants will receive ublituximab SC, using a syringe at one of three different sites of administration. |
| Part 2: Ublituximab SC | EXPERIMENTAL | Participants will be randomized to receive ublituximab SC using either the prefilled pen or a syringe. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Ublituximab + TGR-1202 | EXPERIMENTAL | Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose |
| Ublituximab + TGR-1202 + ibrutinib | EXPERIMENTAL | Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose ibrutinib oral daily dose |
| Ublituximab + TGR-1202 + bendamustine | EXPERIMENTAL | Ublituximab at a fixed IV infusion dose Days 1, 8 and 15 followed by maintenance infusions TGR-1202 oral daily dose Bendamustine at a fixed IV infusion on Days 1 \& 2 |
| Name | Type | Description |
|---|---|---|
| Ublituximab | BIOLOGICAL | Administered as an IV infusion. |
| Placebo | DRUG | IV infusion |
| Teriflunomide | DRUG | Film-coated tablets administered orally. |
| Oral Placebo | DRUG | Administered orally. |
| IV Placebo | DRUG | Administered as an IV infusion. |
| Ibrutinib | DRUG | Administered orally |
| Fingolimod | DRUG | Oral capsule. |
| Prefilled pen | DEVICE | Ublituximab will be administered as an SC injection by prefilled pen. |
| Ublituximab + TGR-1202 | DRUG | Ublituximab IV infusion TGR-1202 oral daily dose |
| Ublituximab + TGR-1202 + ibrutinib | DRUG | Ublituximab IV infusion TGR-1202 oral daily dose Ibrutinib oral daily dose |
| Ublituximab + TGR-1202 + bendamustine | DRUG | Ublituximab IV infusion TGR-1202 oral daily dose Bendamustine IV infusion |
Inclusion Criteria: 1. Diagnosis of RMS (2017 Revised McDonald criteria). 2. Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening. 3. Neurologically stable for \> 30 days prior to Screening and Day 1. 4. Female participants of childbearing potential must consent to use a highly effectiv...