2025-522257-19-00招募中3 期
Ublituximab in Pediatric Participants with Relapsing forms of Multiple Sclerosis (RMS)
Tg Therapeutics Inc.7 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2025年12月22日最近更新:
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- (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)
研究概览
简要总结
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
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •(Part A and B) Age ≥10 years to < 18 years (i.e., have not yet had their 18th birthday at randomization)
- •(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
- •(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)
- •(Part A and B) Expanded Disability Status Scale (EDSS) at screening: 0-5.5, inclusive
- •(Part A and B) B cell count within a specified range
- •(Part A and B) Neurologic stability for ≥ 30 days prior to screening, and between screening and W1D1
- •(Part A and B) Willingness and ability to comply with study and follow-up procedures
- •(Part A and B) Female participants of child-bearing potential who have a negative serum pregnancy test at W1D1
- •(Part C) Participants must have completed Part A (Week 24 visit) or Part B (Week 96 visit) to be eligible for Part C
- •(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
- •(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
- •(Part A and B) Written informed consent from legal representative(s), and age-appropriate assent before any study specific procedures
- •(Part A and B) Diagnosis of RMS (Appendix D – 2017 Revised McDonald Criteria for Diagnosis of MS)
排除标准
- •(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.
- •(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
- •(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
- •(Part A and B) Pregnant or nursing
- •(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)
- •(Part A and B) History or laboratory evidence of coagulation disorders
- •(Part A and B) Peripheral venous access that precludes IV administration and venous blood sampling, unless a central venous access device is in place
- •(Part A and B) Inability to complete an MRI scan and MRI contrast administration
- •(Part A and B) History of cancer, including solid tumors, hematologic malignancies, and carcinoma in situ
- •(Part B) The following antiarrhythmic drugs at Screening: Class Ia (e.g. quinidine, disopyramide) or Class III (e.g. amiodarone, sotalol) anti-arrhythmics.
- •(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.
- •(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)
- •(Part B) Medication that may prolong QTc interval and who have relevant risk factors such as hypokalemia or congenital QT prolongation
- •(Part B) Concomitant medications that are strong inhibitors of CYP4F2 and CYP3A4, (e.g., itraconazole)
- •(Part B) Diagnosis of macular edema
- •(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
- •(Part B) History of medically refractory epilepsy
- •(Part B) Laboratory-based criteria
- •(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
- •(Part A and B) Current participation in any other interventional clinical study
- •(Part A and B) Participants with significantly impaired bone marrow function or significant leukopenia or thrombocytopenia
- •(Part A and B) History of renal impairment
- •(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
- •(Part A and B) Confirmed diagnosis of Gilberts syndrome
- •(Part B) Treatment with fingolimod or other S1P1 modulators at any time (siponimod, ozanimod, ponesimod).
研究组 & 干预措施
ublituximab
Experimental
Participants receiving ublituximab
干预措施: ublituximab (Drug)
结局指标
主要结局
(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)
(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)
(Part A) Percentage of patients with CD19+ B cell at a defined level
(Part A) Percentage of patients with CD19+ B cell at a defined level
次要结局
- 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)
- Part A: Pharmacology a. Serum concentrations of ublituximab b. Percentage of participants with anti-drug antibodies (ADAs) to ublituximab
- 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)
- 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
研究者
Clinical Support Team
Scientific
Tg Therapeutics Inc.
研究点 (7)
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