UBLITUXIMAB for Relapsing multiple sclerosis

Inclusion criteria

• {"criterion_text":"- 18-65 years old"}
• {"criterion_text":"- Part C: Participants currently treated with an anti-CD20 agent for at least 6 months and meet the washout requirements listed in Appendix B – Washout Requirement for Prior Disease Modifying Therapies prior to W1D1. Note: Any exposure to therapies listed in Exclusion Criteria #14 remain exclusionary"}
• {"criterion_text":"- Part C: Discontinuation of current anti-CD20 must be due to suboptimal experience defined by having any of the following: a. One or more clinically reported relapse(s) b. One or more T1 Gd-enhanced lesion(s) c. Two or more new or enlarging T2 lesions on MRI d. Experiencing wearing-off effect e. B-cell repopulation between doses f. Persistent IRRs including on most recent anti-CD20 administration g. Inability to tolerate 2-hour infusion of ocrelizumab"}
• {"criterion_text":"- Part C: EDSS score ≤5.5 at screening"}
• {"criterion_text":"- Part C: Neurologically stable days prior to first dose of ublituximab"}
• {"criterion_text":"- Part C: Acceptable laboratory parameters at screening"}
• {"criterion_text":"- Part C: Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for 6 months after the last dose of ublituximab"}
• {"criterion_text":"- Part C: Willing and able to comply with the study protocol in the investigator’s judgment"}
• {"criterion_text":"- Diagnosis of RMS (2017 Revised McDonald criteria)"}
• {"criterion_text":"- Participants must meet one of the following prior treatment definitions: a.\tParticipants naïve to treatment. b.\tParticipants previously treated with a DMT who have discontinued treatment prior to consent and meet the washout requirements listed in Appendix B – Washout Requirement for Prior Disease Modifying Therapies prior to W1D1. Note: Therapies listed in Exclusion Criteria #14 remain exclusionary."}
• {"criterion_text":"- EDSS score ≤ 5.5 at screening"}
• {"criterion_text":"- Neurologically stable prior to first dose of ublituximab"}
• {"criterion_text":"- Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for protocol-specified time after the last dose of ublituximab"}
• {"criterion_text":"- Acceptable laboratory parameters at screening"}
• {"criterion_text":"- Part C: 18-65 years old"}
• {"criterion_text":"- Part C: Diagnosis of RMS (2017 Revised McDonald criteria)"}

Exclusion criteria

• {"criterion_text":"- Any severe or uncontrolled medical condition that could affect the participant’s ability to participate"}
• {"criterion_text":"- History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML)"}
• {"criterion_text":"- Receipt of any live or live-attenuated vaccines (including vaccines for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration"}
• {"criterion_text":"- Females who are pregnant or nursing"}
• {"criterion_text":"- Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma"}
• {"criterion_text":"- Participants who have ever received ublituximab, alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab (including for non-MS indications)"}
• {"criterion_text":"- Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS)"}
• {"criterion_text":"- Active chronic (or stable but treated with immune therapy) disease of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn’s disease, ulcerative colitis, etc.) or immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency, etc.)"}
• {"criterion_text":"- Current evidence or known history of clinically significant infection, including: chronic, recurrent, or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to chronic urinary tract infection, chronic pulmonary infection with bronchiectasis, tuberculosis, or active hepatitis C virus (HCV)"}
• {"criterion_text":"- Previous serious opportunistic or atypical infection"}
• {"criterion_text":"- Evidence of chronic active or history of hepatitis B virus (HBV) as evidenced by a detectable hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb), or chronic hepatitis C infection. Participants with positive HCV Ab are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA"}

Primary endpoints

• {"endpoint_text":"- Part A: The proportion of participants with no change or reduction in number of T1 Gd-enhancing lesions from baseline to Week 48","definition_or_measurement_approach":"Proportion measured by change in number of T1 Gd-enhancing lesions on MRI from baseline to Week 48"}
• {"endpoint_text":"- Part B: PK (AUC) over the first 16 weeks (AUC0-W16)","definition_or_measurement_approach":"Pharmacokinetic area under the concentration-time curve from baseline to Week 16 (AUC0-W16)"}
• {"endpoint_text":"- Part C: Proportion of participants with no change or reduction in number of T1 Gd-enhancing lesions","definition_or_measurement_approach":"Proportion measured by number of T1 Gd-enhancing lesions on MRI (as stated in main objective for Part C)"}

Secondary endpoints

• {"endpoint_text":"- Part A: The proportion of participants free of T1 Gd-enhancing lesions at Week 48","definition_or_measurement_approach":"Proportion of participants with zero T1 Gd-enhancing lesions on MRI at Week 48"}
• {"endpoint_text":"- Part A: The proportion of participants experiencing IRRs as reported by the Investigator","definition_or_measurement_approach":"Investigator-reported incidence of infusion-related reactions (IRRs)"}
• {"endpoint_text":"- Part A: Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at Week 24 and Week 48","definition_or_measurement_approach":"TSQM-9 patient-reported treatment satisfaction scores at Weeks 24 and 48"}
• {"endpoint_text":"- Part A: Pharmacokinetics of ublituximab","definition_or_measurement_approach":"Pharmacokinetic assessments of ublituximab (unspecified PK parameters)"}
• {"endpoint_text":"- Part B: The proportion of participants who experience any grade treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Incidence of any grade TEAEs as collected during the study"}
• {"endpoint_text":"- Part B: The proportion of participants experiencing IRR as reported by the Investigator","definition_or_measurement_approach":"Investigator-reported infusion-related reactions (IRRs)"}
• {"endpoint_text":"- Part B: The number of T1 Gd-enhancing lesions per MRI scan at Week 24 and Week 48","definition_or_measurement_approach":"Count of T1 Gd-enhancing lesions on MRI at Weeks 24 and 48"}
• {"endpoint_text":"- Part B: PK (Cmax) at Day 1 and Day 15","definition_or_measurement_approach":"Maximum observed concentration (Cmax) on Day 1 and Day 15"}
• {"endpoint_text":"- Part B: The proportion of participants with CD19+ B-cell counts below a specific level at all timepoints","definition_or_measurement_approach":"Proportion with CD19+ B-cell counts below a specified threshold at all measured timepoints"}
• {"endpoint_text":"- Part C: Proportion of participants free of T1 Gd-enhancing lesions","definition_or_measurement_approach":"Proportion with zero T1 Gd-enhancing lesions on MRI (timepoint as per Part C assessments)"}
• {"endpoint_text":"- Part C: The proportion of participants experiencing IRRs as reported by the Investigator","definition_or_measurement_approach":"Investigator-reported infusion-related reactions (IRRs)"}
• {"endpoint_text":"- Part C: Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at each timepoint","definition_or_measurement_approach":"TSQM-9 patient-reported treatment satisfaction scores collected at each study timepoint"}
• {"endpoint_text":"- Part C: Change from baseline in PROMIS-Fatigue-MS-8a at each timepoint","definition_or_measurement_approach":"Change from baseline in PROMIS-Fatigue-MS-8a patient-reported fatigue scores at each timepoint"}
• {"endpoint_text":"- Part C: Neuro-QOL at each timepoint","definition_or_measurement_approach":"Neuro-QOL patient-reported outcomes measured at each timepoint"}

Poland

Earliest CTIS Part Ii Submission Date

13-02-2025

Latest Decision Or Authorization Date

14-12-2025

Processing Time Days

304

Number Of Sites

10

Number Of Participants

233

Primary sponsor

Full Name

Tg Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Third parties

• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"sponsorDuties codes: [14, 15], value: IMP importation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"sponsorDuties codes: [8]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"sponsorDuties codes: [3, 6, 7]","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Neurorx Research Inc.","duties_or_roles":"sponsorDuties codes: [15], value: Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Archives","duties_or_roles":"sponsorDuties codes: [15], value: Biological samples archiving","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"sponsorDuties codes: [14, 15], value: Other - IMP importation","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Voxel S.A.","duties_or_roles":"sponsorDuties codes: [15], value: MRI scan provider","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Poland","full_name":"Salus International Sp. z o.o.","duties_or_roles":"sponsorDuties codes: [15], value: AxMPs supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Octave Bioscience, Inc","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Health care"}
• {"country":"Poland","full_name":"Brillance Sp. z o.o.","duties_or_roles":"sponsorDuties codes: [1, 12, 15], values: Management of compensation/reimbursement for patients; Legal representation in the EU; Management/other roles","organisation_type":"Pharmaceutical company"}