Ublituximab in Pediatric Participants with Relapsing forms of Multiple Sclerosis (RMS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tg Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 May 2026 → ongoing

Decision date (initial)

2025-12-22

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, Pharmacodynamic, Others, Pharmacokinetic, Efficacy

Part A:
- To assess the pharmacokinetics and relative bioavailability of ublituximab in patients ages 10 to < 18 years with RMS
- To assess the pharmacodynamics of ublituximab in patients ages 10 to < 18 years with RMS
Part B:
- To establish non-inferiority of ublituximab compared with fingolimod in children with RMS between 10
Part C:
- To evaluate the long-term safety and efficacy of ublituximab in RMS in pediatric participants

Secondary objectives 2

1. Part A: To assess the safety, tolerability, and efficacy of ublituximab in patients ages 10 to < 18 years with RMS
2. Part B: To assess the safety, tolerability and efficacy of ublituximab in patients ages 10 to < 18 years with RMS

Conditions and MedDRA coding

Relapsing Multiple Sclerosis

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

EMA paediatric investigation plan (PIP)

EMEA-002889-PIP02-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. (Part A and B) Age ≥10 years to < 18 years (i.e., have not yet had their 18th birthday at randomization)
2. (Part A and B) Neurologic stability for ≥ 30 days prior to screening, and between screening and W1D1
3. (Part A and B) Willingness and ability to comply with study and follow-up procedures
4. (Part A and B) Female participants of child-bearing potential who have a negative serum pregnancy test at W1D1
5. (Part C) Participants must have completed Part A (Week 24 visit) or Part B (Week 96 visit) to be eligible for Part C
6. (Part A and B) Female participants of child-bearing potential must agree to use a medically acceptable method of contraception throughout the study period and for 20 Weeks after the last dose of ublituximab / intravenous (IV) placebo or 8 weeks after the last dose of fingolimod / oral placebo, whichever is later Appendix A – Contraception Guidance see for additional details
7. (Part A and B) Fertile male subjects participating in the study who are sexually active with women of child-bearing potential, must agree to use a condom during the treatment period and for 20 Weeks after the last dose of ublituximab / intravenous (IV) placebo or 8 weeks after the last dose of fingolimod / oral placebo, whichever is later
8. (Part A and B) Written informed consent from legal representative(s), and age-appropriate assent before any study specific procedures
9. (Part A and B) Diagnosis of RMS (Appendix D – 2017 Revised McDonald Criteria for Diagnosis of MS)
10. (Part A and B) Disease History: a. At least one relapse experienced in the previous 12 months or b. At least two relapses in the previous 24 months and ≥1 Gd+ lesion on T1-weighted brain MRI at any time within the previous 12 months or c. ≥1 new T2 lesions or Gd-enhancing T1 lesions compared to prior MRI conducted within 12 months
11. (Part A and B) Must have completed their locally recommended vaccination schedule and have evidence of immunity to varicella-zoster virus, mumps, measles,rubella, diphtheria, tetanus and pertussis at Screening (See Appendix G –Vaccine Guidance)
12. (Part A and B) Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
13. (Part A and B) B cell count within a specified range

Exclusion criteria 25

1. (Part A and B) Known presence or suspicion of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis, neuromyelitis optica or neuromyelitis optica spectrum disorders and any neurologic, somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development.
2. (Part A and B) History of a severe allergic or anaphylactic reaction to humanized or murine (mAb) or known hypersensitivity to any component of ublituximab solution, fingolimod product, or to premedications/rescue medication (corticosteroids, diphenhydramine)
3. (Part A and B) Significant concurrent, uncontrolled medical condition including, but not limited to, cardiac, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric, immunological, or neurological disease which could affect the participant’s safety, impair the participant’s reliable participation in the study, impair the evaluation of endpoints, or necessitate the use of medication not allowed by the protocol, as determined by the PI of the study
4. (Part A and B) Current participation in any other interventional clinical study
5. (Part A and B) Participants with significantly impaired bone marrow function or significant leukopenia or thrombocytopenia
6. (Part A and B) History of renal impairment
7. (Part A and B) History of liver disease, including but not limited to: a. Presence of clinically significant chronic liver or biliary disease b. Moderate or severe hepatic impairment defined as Child Pugh Score B or C, respectively, based on measurement of total bilirubin, serum albumin, International Normalized Ratio (INR) and as well as on presence /absence and severity of ascites and hepatic encephalopathy c. Relevant abnormal laboratory values at screening or first infusion
8. (Part A and B) Confirmed diagnosis of Gilberts syndrome
9. (Part B) Treatment with fingolimod or other S1P1 modulators at any time (siponimod, ozanimod, ponesimod).
10. (Part A and B) Current evidence or known history of clinically significant infection including: a. Chronic or ongoing active infectious disease requiring long term systemic treatment such as, but not limited to: Progressive multifocal leukoencephalopathy (PML), chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis (TB), or active hepatitis B or C. b. Previous serious opportunistic or atypical infections
11. (Part A and B) Viral Screening a. 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) b. Any evidence of hepatitis C virus (HCV) infection as evidenced by either positive HCV-Ab or positive HCV RNA. c. Seropositive for human immunodeficiency virus (HIV) antibody d. Latent or active TB infection as evidenced by a positive Interferon Gamma Release Assay (IGRA) blood test conducted at screening
12. (Part A and B) Pregnant or nursing
13. (Part A and B) Receipt of a live or live-attenuated vaccine within 4 weeks prior to first study drug administration (Week 1 Day 1) (i.e., varicella-zoster virus or MMR)
14. (Part A and B) History or laboratory evidence of coagulation disorders
15. (Part A and B) Peripheral venous access that precludes IV administration and venous blood sampling, unless a central venous access device is in place
16. (Part A and B) Inability to complete an MRI scan and MRI contrast administration
17. (Part A and B) History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
18. (Part B) The following antiarrhythmic drugs at Screening: Class Ia (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) anti-arrhythmics.
19. (Part B) Concurrently treated with heart-rate-lowering drugs at Screening e.g.: Beta blockers, heart rate lowering calcium channel blockers (e.g. verapamil, diltiazem or ivabradine), digoxin, anticholinesteratic agents, pilocarpine. Advice from a cardiologist should be sought regarding the switch to nonheart rate lowering medicinal products.
20. (Part B) Medication that may prolong QTc interval and who have relevant risk factors such as hypokalemia or congenital QT prolongation
21. (Part B) Concomitant medications that are strong inhibitors of CYP4F2 and CYP3A4, (e.g., itraconazole)
22. (Part B) Diagnosis of macular edema
23. (Part B) Severe cardiac disease or significant findings on the screening electrocardiogram (ECG), such as: a. History of symptomatic bradycardia or recurrent syncope b. Known ischemic heart disease History of congenital heart disease (except conditions such as small patent ductus arteriosus, atrial septal defect, ventricular septal defect, or an ECG or rhythm abnormality, which have been assessed by a pediatric cardiologist and considered to be clinically insignificant). d. Cerebrovascular disease e. History of myocardial infarction f. Congestive heart failure g. History of cardiac arrest h. Systolic or diastolic blood pressure meeting criteria for Stage 2 hypertension in Flynn et al., 2017 (See Appendix B – Definitions of Blood Pressure Categories (Note: patients with controlled stage 1 hypertension at baseline are eligible) i. Baseline heart rate greater than the 99th percentile or less than the 5th percentile for age (Fleming et al., 2011;Appendix C – Proposed Heart Rate cutoffs (beats/Minute) based on centile Charts ) j. Severe untreated sleep apnea. k. Sick sinus syndrome or sino-atrial heart block l. Defined QTcF interval or relevant risk factors for QT prolongation (e.g. hypokalaemia, hypomagnesemia, congenital QT prolongation) or treatment with QT prolonging drugs with a known risk of Torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) or history of familial long QT syndrome or known family history of Torsades de Pointes. m. Second degree Mobitz type II or higher AV block
24. (Part B) History of medically refractory epilepsy
25. (Part B) Laboratory-based criteria

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. (Part C) Safety a. Incidence and severity of AEs, with severity determined according to NCI CTCAE v5.0 b. Suicidal Ideation Columbia-Suicide Severity Rating Scale (C-SSRS)
2. (Part A) Percentage of patients with CD19+ B cell at a defined level

Secondary endpoints 4

1. Part A: Safety a. Incidence and severity of AEs, with severity determined according to NCI CTCAE v5.0 b. Suicidal ideation Columbia-Suicide Severity Rating Scale (C-SSRS)
2. Part A: Pharmacology a. Serum concentrations of ublituximab b. Percentage of participants with anti-drug antibodies (ADAs) to ublituximab
3. Part B: Safety a. Incidence and severity of AEs, with severity determined according to NCI CTCAE v5.0 b. Suicidal ideation Columbia-Suicide Severity Rating Scale (C-SSRS)
4. Part B: Pharmacology a. Calculated PK parameters of ublituximab b. CD19+ B cell counts c. Percentage of participants with Treatment Emergent Anti-Drug Antibody(TE-ADAs) to ublituximab

Investigational products

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

Test 1

Comparator 1

Placebo 2

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 11

Locations

2 EU/EEA countries · 8 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 41 files

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

Application history

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