Evaluation of intravenous or subcutaneous administration of ublituximab in patients with autoimmune diseases

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

15 May 2024 → ongoing

Decision date (initial)

2024-05-06

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: Pharmacodynamic, Safety, Pharmacokinetic

To evaluate the pharmacokinetics and pharmacodynamics of intravenous or subcutaneous administration of ublituximab in patients with autoimmune diseases

Conditions and MedDRA coding

Relapsing multiple sclerosis

Regulatory references

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 10

1. (MS) 18-65 years old
2. (MS) Diagnosis of RMS (2017 Revised McDonald criteria)
3. (MS) Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening
4. (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
5. (MG) Oculobulbar, bulbar or generalized MG (gMG) ≥18 years of age at the time of signing the informed consent
6. (MG) Diagnosed with MG at least 6 months (180 days) prior to the date of signing the informed consent
7. (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
8. (MG) Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening
9. (MG) MG-ADL ≥ 6 at screening
10. (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 16

1. (MS) Primary-progressive MS (PPMS) or inactive Secondary Progressive MS (SPMS)
2. (MS, MG) Females who are pregnant or nursing
3. (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
4. (MS, MG) Unwillingness or inability to comply with study and/or follow-up procedures outlined in the protocol.
5. (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.)
6. (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.
7. (MG) Muscle weakness affecting only ocular or periocular muscles (MGFA class I)
8. (MG) History of thymectomy, thymomectomy, or any thymic surgery within the 12 months prior to screening
9. (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
10. (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
11. (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)
12. (MS, MG) History of serious opportunistic or atypical infections, including human immunodeficiency virus (HIV)
13. (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
14. (MS, MG) History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML)
15. (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
16. (MS, MG) Any severe or uncontrolled medical condition that could affect the participant’s ability to participate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Pharmacokinetic assessment of intravenous and subcutaneous administration of ublituximab
2. B-cell count following intravenous and subcutaneous administration of ublituximab

Investigational products

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

Test 3

Auxiliary 5

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 14

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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