Pharmacokinetic and Pharmacodynamic Assessment of Ublituximab in Myasthenia Gravis and Relapsing Multiple Sclerosis with Methylprednisolone Combination
- Trial ID
- 2023-509555-13-00
- Protocol
- TG1101-RMS-SC101
- Sponsor
- Tg Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **pharmacokinetics** and **pharmacodynamics** of intravenous or subcutaneous administration of **ublituximab** in patients with autoimmune diseases, specifically **Myasthenia Gravis** and **Relapsing Multiple Sclerosis**. Understanding the pharmacokinetic and pharmacodynamic profiles of ublituximab is clinically relevant as it provides insights into the drug's absorption, distribution, metabolism, and excretion, as well as its biological effects, which are crucial for optimizing therapeutic strategies and improving patient outcomes in these autoimmune conditions.
Participants
The clinical trial involves participants diagnosed with **Myasthenia Gravis** and **Relapsing Multiple Sclerosis**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants are required to have a stable health status, particularly in terms of their current treatment regimens for Myasthenia Gravis, which may include azathioprine, immunosuppressive therapies, oral corticosteroids, or cholinesterase inhibitors. The trial population was selected based on specific inclusion criteria, such as a confirmed diagnosis of the respective autoimmune diseases and stability in their treatment plans. The study also considers lifestyle factors, such as the use of effective contraception for female participants of childbearing potential. The sponsor has not provided information regarding the total number of participants. The trial includes a vulnerable population, ensuring careful consideration of ethical standards in the study design.
Plans and Procedures
The clinical trial is designed to evaluate the **pharmacokinetics** and **pharmacodynamics** of **ublituximab** administered either intravenously or subcutaneously in patients with autoimmune diseases, specifically **Myasthenia Gravis** and **Relapsing Multiple Sclerosis**. This is a phase 1, randomized, double-blind, controlled study. The trial is expected to commence on May 7, 2024, and conclude by January 5, 2027. The study will involve multiple visits, starting with an inclusion visit to screen participants based on specific criteria, including age, diagnosis, and treatment history. Participants will be required to have a confirmed diagnosis of either Myasthenia Gravis or Relapsing Multiple Sclerosis, with additional criteria for each condition.
Following the screening, eligible participants will be randomized to receive either intravenous or subcutaneous administration of ublituximab. The primary endpoints include the pharmacokinetic assessment and B-cell count following administration. Participants will attend regular follow-up visits to monitor these parameters and assess safety and tolerability. The end-of-study visit will mark the completion of the trial for each participant, where final assessments will be conducted. The expected length of participant involvement is approximately 32 months, depending on the individual start date within the recruitment period.
Conditions that may lead to early termination from the study include adverse reactions to the investigational product, non-compliance with study procedures, or withdrawal of consent. Participants will be monitored closely throughout the trial to ensure safety and adherence to the protocol. The study aims to provide valuable insights into the effects of ublituximab in treating autoimmune diseases, contributing to the development of effective therapeutic strategies.
Treatment
The clinical trial involves the administration of **ublituximab**, a recombinant chimeric monoclonal antibody targeting CD20, which is provided in two pharmaceutical forms: a **concentrate for solution for infusion** and a **solution for injection**. Ublituximab is administered via **intravenous infusion** and **subcutaneous injection**. The dosing schedule and frequency are determined based on the pharmacokinetic and pharmacodynamic evaluation objectives of the study. Participant compliance is monitored through regular assessments and documentation of infusion or injection sessions.
**Methylprednisolone** is utilized as a non-experimental treatment in the study. It is provided as a **solution for injection** and administered via **injection**. The dosage and frequency are aligned with standard clinical practices for managing autoimmune diseases, ensuring participant safety and therapeutic efficacy.
**Cetirizine** is included as a non-experimental treatment, available in **tablet** form and administered **orally**. The dosage and administration frequency follow established guidelines for antihistamine use in managing allergic symptoms associated with autoimmune conditions.
**Paracetamol** is provided as a **tablet** for **oral** administration. It serves as a supportive treatment for managing pain and fever in participants, with dosing schedules adhering to standard therapeutic protocols.
**Diphenhydramine** is administered in **tablet** form via the **oral** route. It is used to manage allergic reactions and symptoms, with dosage and frequency based on established clinical guidelines for antihistamine use.
**Dexamethasone** is included as a **tablet** for **oral** administration. It is used as an anti-inflammatory agent, with dosing schedules tailored to the needs of participants with autoimmune diseases, following standard medical practices.
**Sodium chloride** is provided as a **solution for infusion** and administered via **intravenous infusion**. It serves as a supportive treatment to maintain fluid balance and electrolyte levels during the trial, with administration protocols following standard clinical guidelines.
Efficacy
The efficacy of the clinical trial evaluating **ublituximab** in patients with autoimmune diseases will be assessed through primary endpoints focused on pharmacokinetic and pharmacodynamic parameters. Specifically, the primary endpoints include the pharmacokinetic assessment of both intravenous and subcutaneous administration of **ublituximab**, as well as the measurement of B-cell count following these administrations. These endpoints are designed to provide insights into the drug's behavior in the body and its biological effects, which are critical for understanding its potential therapeutic benefits.
Inclusion and Exclusion Criteria
Inclusion Criteria
- (MS) 18-65 years old
- (MS) Diagnosis of RMS (2017 Revised McDonald criteria)
- (MS) Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening
- (MS) Female participants of childbearing potential must consent to use an effective method of contraception from consent and for 6 months after the last dose of ublituximab
- (MG) Oculobulbar, bulbar or generalized MG (gMG) ≥18 years of age at the time of signing the informed consent
- (MG) Diagnosed with MG at least 6 months (180 days) prior to the date of signing the informed consent
- (MG) Confirmation of eligibility by: i. Positive serologic test for anti-AChR Abs or anti-MuSK Abs as confirmed at screening, AND One of the following (either historical or during screening): a. Abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation b. Positive anticholinesterase test (eg, edrophonium chloride test) c. Demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician
- (MG) Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening
- (MG) MG-ADL ≥ 6 at screening
- (MG) Patients receiving treatment with ANY of the following must have been receiving treatment and on a stable dose for the time periods specified below prior to the date of the informed consent: a. Azathioprine (AZA): Must have been on AZA for ≥ 6 months (180 days) and have been on a stable dose for ≥ 2 months (60 days). Dose may not exceed 3 mg/kilogram (kg)/day. b. Immunosuppressive therapies (IST) (i.e., mycophenolate mofetil [MMF], methotrexate [MTX], cyclosporine [CYC], tacrolimus [TAC], or cyclophosphamide [CY]), must have been on the IST for ≥ 3 months (90 days) and have been on a stable dose for ≥ 1 month (30 days). c. Oral corticosteroids (i.e., prednisone), must have been on a stable dose for ≥ 4 weeks (28 days). Dose may not exceed 40 milligram (mg)/day or > 80 mg over a 2-day period (or equivalent dose of other corticosteroids). d. A cholinesterase inhibitor (i.e., pyridostigmine), must have been on a stable dose for ≥ 2 weeks (14 days). Dose may not exceed 480 mg/day.
Exclusion Criteria
- (MS) Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS)
- (MS, MG) Females who are pregnant or nursing
- (MS) History of cancer except: - If considered likely to be cured (with supporting documentation from the treating oncologist if possible), - Is not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the Investigator, is not likely to require treatment in the ensuing 3 years, - Considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible), - Adequately treated and/or resolved basal or in situ squamous carcinomas of the skin are permitted
- (MS, MG) Unwillingness or inability to comply with study and/or follow-up procedures outlined in the protocol.
- (MS) 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.)
- (MG) History of cancer, including any active or untreated thymoma or history of thymic carcinoma or thymic malignancy, with the following exceptions: a. If considered likely to be cured (with supporting documentation from the treating oncologist if possible), b. Is not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the Investigator, is not likely to require treatment in the ensuing 3 years, c. Considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible), Adequately treated and/or resolved basal or in situ squamous carcinomas of the skin are permitted e. Treated patients with history of thymoma other than thymic carcinoma corresponding to clinical stage 1 and 2 with no evidence of recurrence as defined by a recent negative imaging study (computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) scan within 6 months of enrollment) are eligible for enrollment.
- (MG) Muscle weakness affecting only ocular or periocular muscles (MGFA class I)
- (MG) History of thymectomy, thymomectomy, or any thymic surgery within the 12 months prior to screening
- (MG) Clinical features that, in the opinion of the Investigator, are consistent with MG crisis/exacerbation or Clinical Deterioration, at the time of the signing of the informed consent, or at any time prior to enrollment
- (MS, MG) History of life-threatening injection/infusion related reaction (IRR), hypersensitivity, or anaphylactic reaction with anti-CD20 therapy, components of ublituximab solution or pre-treatment medications
- (MS, MG) 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)
- (MS, MG) History of serious opportunistic or atypical infections, including human immunodeficiency virus (HIV)
- (MS, MG) History of active 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 hepatitis C virus antibody (HCV Ab) are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
- (MS, MG) History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML)
- (MS, MG) Receipt of any live or live-attenuated vaccines (including vaccines for varicellazoster virus or measles) within 4 weeks prior to first study drug administration
- (MS, MG) Any severe or uncontrolled medical condition that could affect the participant’s ability to participate
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Not Recruiting | 07 May 2024 | 164 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
DIPHENHYDRAMINE | Other | — | ORAL | — | — | SUB07211MIG |
DEXAMETHASONE | Other | — | ORAL | — | — | SUB07017MIG |
METHYLPREDNISOLONE | Other | — | INJECTION | — | — | SUB08872MIG |
Ublituximab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | — | — | PRD12001815 |
ublituximab | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS INJECTION | — | — | PRD11075484 |
ublituximab | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | — | — | PRD5447378 |
PARACETAMOL | Other | — | ORAL | — | — | SUB09611MIG |
CETIRIZINE | Other | — | ORAL | — | — | SUB07451MIG |