Dataset Information

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

ABSTRACT:

Background

Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs.

Objective

The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis.

Methods

This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150?mg over 1-4?hours on day 1 and 450-600?mg over 1-3?hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion.

Results

In all cohorts (N?=?48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p?=?0.003) and a 10.6% decrease in T2 lesion volume (p?=?0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA).

Conclusion

Ublituximab was safely infused as rapid as 1?hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.

SUBMITTER: Fox E

PROVIDER: S-EPMC7897779 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

Fox Edward E Lovett-Racke Amy E AE Gormley Matthew M Liu Yue Y Petracca Maria M Cocozza Sirio S Shubin Richard R Wray Sibyl S Weiss Michael S MS Bosco Jenna A JA Power Sean A SA Mok Koby K Inglese Matilde M

Multiple sclerosis (Houndmills, Basingstoke, England) 20200430 3

<h4>Background</h4>Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs.<h4>Objective</h4>The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis.<h4>Methods</h4>This is a phase 2, placebo-controlle ...[more]

PMID: 32351164

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Project description:OBJECTIVE:This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20(+) B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. METHODS:Fifteen patients with CD20(+) B-cell NHL received dose-escalating SCT400 infusions (250 mg/m(2): n=3; 375 mg/m(2): n=9; 500 mg/m(2): n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. RESULTS:No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m(2) dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m(2) to 500 mg/m(2), the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. CONCLUSIONS:SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20(+) B-cell NHL.

Dataset Information

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

Background

Objective

Methods

Results

Conclusion

Publications

A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis.

Similar Datasets

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