Evaluating safety, efficacy and pharmacokinetics of a modified regimen of ublituximab (ENHANCE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tg Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Jun 2025 → ongoing

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TG Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy, Pharmacokinetic

Part A: To assess efficacy of a modified regimen of ublituximab as measured by T1 Gd-enhancing lesions
Part B: To demonstrate non-inferiority of pharmacokinetics of ublituximab IV infusion on Day 1 compared to the conventional IV regimen of 150 mg on Day 1 and 450 mg on Day 15
Part C: To assess efficacy of ublituximab as measured by T1 Gd-enhancing lesions in participants who had a suboptimal experience on prior anti-CD20 therapy

Secondary objectives 13

1. Part A: To assess the proportion of participants free of T1 Gd-enhancing lesions
2. Part A: To assess the tolerability of ublituximab infusions
3. Part A: To assess treatment satisfaction in ublituximab treated participants
4. Part B: Characterize the safety profile of ublituximab IV infusion on Day 1
5. Part B: Evaluate the tolerability and safety of ublituximab IV infusion on Day 1
6. Part B: Evaluate the efficacy of ublituximab IV infusion on Day 1
7. Part B: Characterize the pharmacokinetics of ublituximab IV infusion on Day 1
8. Part B: Characterize the pharmacodynamics of ublituximab IV infusion on Day 1
9. Part C: To assess the proportion of participants free of T1 Gd-enhancing lesions
10. Part C: To assess the tolerability of ublituximab infusions
11. Part C: To assess treatment satisfaction in ublituximab treated participants
12. Part C: To assess fatigue in ublituximab treated participants
13. Part C: To assess quality of life in ublituximab treated participants

Conditions and MedDRA coding

Relapsing multiple sclerosis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002889-PIP01-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 18-65 years old
2. Diagnosis of RMS (2017 Revised McDonald criteria)
3. Participants must meet one of the following prior treatment definitions: a. Participants naïve to treatment. b. Participants 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.
4. EDSS score ≤ 5.5 at screening
5. Neurologically stable prior to first dose of ublituximab
6. 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
7. Acceptable laboratory parameters at screening
8. Part C: 18-65 years old
9. Part C: Diagnosis of RMS (2017 Revised McDonald criteria)
10. 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
11. 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
12. Part C: EDSS score ≤5.5 at screening
13. Part C: Neurologically stable days prior to first dose of ublituximab
14. Part C: Acceptable laboratory parameters at screening
15. 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
16. Part C: Willing and able to comply with the study protocol in the investigator’s judgment

Exclusion criteria 11

1. Any severe or uncontrolled medical condition that could affect the participant’s ability to participate
2. Females who are pregnant or nursing
3. Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma
4. Participants who have ever received ublituximab, alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab (including for non-MS indications)
5. Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS)
6. 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.)
7. 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)
8. Previous serious opportunistic or atypical infection
9. 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
10. History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML)
11. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A: The proportion of participants with no change or reduction in number of T1 Gd-enhancing lesions from baseline to Week 48
2. Part B: PK (AUC) over the first 16 weeks (AUC0-W16)
3. Part C: Proportion of participants with no change or reduction in number of T1 Gd-enhancing lesions

Secondary endpoints 14

1. Part A: The proportion of participants free of T1 Gd-enhancing lesions at Week 48
2. Part A: The proportion of participants experiencing IRRs as reported by the Investigator
3. Part A: Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at Week 24 and Week 48
4. Part A: Pharmacokinetics of ublituximab
5. Part B: The proportion of participants who experience any grade treatment-emergent adverse events (TEAEs)
6. Part B: The proportion of participants experiencing IRR as reported by the Investigator
7. Part B: The number of T1 Gd-enhancing lesions per MRI scan at Week 24 and Week 48
8. Part B: PK (Cmax) at Day 1 and Day 15
9. Part B: The proportion of participants with CD19+ B-cell counts below a specific level at all timepoints
10. Part C: Proportion of participants free of T1 Gd-enhancing lesions
11. Part C: The proportion of participants experiencing IRRs as reported by the Investigator
12. Part C: Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores at each timepoint
13. Part C: Change from baseline in PROMIS-Fatigue-MS-8a at each timepoint
14. Part C: Neuro-QOL at each timepoint

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tg Therapeutics Inc.

Sponsor organisation

Tg Therapeutics Inc.

Address

3020 Carrington Mill Boulevard Suite 475

City

Morrisville

Postcode

27560-5435

Country

United States

Scientific contact point

Organisation

Tg Therapeutics Inc.

Contact name

Clinical Support Team

Public contact point

Organisation

Tg Therapeutics Inc.

Contact name

Clinical Support Team

Third parties 12

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications