EMD Serono (a business of Merck KGaA, Darmstadt, Germany)

Author Of 1 Presentation

Clinical Trials Poster Presentation

P0235 - Safety of the Bruton’s tyrosine kinase inhibitor evobrutinib in relapsing multiple sclerosis during an open-label extension to a phase II study (ID 1687)

Speakers
Presentation Number
P0235
Presentation Topic
Clinical Trials

Abstract

Background

In a Phase II randomized study (NCT02975349) in patients with relapsing MS, evobrutinib (EVO) 75 mg twice-daily (BID) reduced total T1 Gd+ lesions (primary endpoint) and annualized relapse rate (ARR) over 24 weeks versus placebo, with efficacy maintained through Week 108. EVO was generally well tolerated.

Objectives

To describe the safety profile of EVO in the long-term treatment of MS by reporting detailed safety data from the study’s open-label extension (OLE) over 60 weeks.

Methods

In the 48-week double-blind period (DBP), patients received EVO 25 mg once-daily (QD) or 75 mg QD, 75 mg BID, or placebo for the first 24 weeks. All arms continued with the original treatment assignment until 48 weeks, except placebo patients who were switched to EVO 25 mg QD. At Week 48, all patients could enter the OLE, where treatment was initially EVO 75 mg QD (for a median of ~48 weeks) before switching to 75 mg BID. Safety was assessed throughout the OLE by the nature, severity, and occurrence of treatment emergent adverse events (TEAEs) by NCI-CTCAE v4.03 criteria, as well as vital signs, ECGs, and clinical laboratory safety parameters.

Results

Of 213 patients who received EVO during the double-blind period, 164 (77%) entered the OLE (safety analysis population) and 148 (90%) completed 60 weeks of treatment. Overall, 107 (65.2%) patients had a treatment emergent adverse event (TEAE), the majority of which were mild (47.6%) or moderate (36.0%), and none led to death. TEAEs were balanced across previous DBP treatment groups; the most frequent TEAEs over the OLE period, including the dose-switch, were nasopharyngitis (7.9%, Grade 2 or less), increased lipase (7.9%, Grade 3 or less), upper respiratory tract infection (6.1%, Grade 2 or less), and urinary tract infection (4.9%, Grade 2 or less); analysis of TEAEs by exposure-adjusted incidence rate showed no evidence of an increase after patients switched to 75 mg BID. Thirteen patients (7.9%) reported a serious TEAE, most frequently related to infections (6 patients, not treatment-related). Five patients (3.0%) had a TEAE during the OLE that led to treatment withdrawal, of which 3 were considered related to treatment (nausea, increased lipase, and increased lipase and amylase). The incidence of overall infections in the OLE was similar to that observed in the DBP. Transient elevated liver aminotransferases reported in the 48-week DBP were not observed in the OLE after prolonged treatment or after the switch to 75 mg BID. No adverse ECG findings were noted across all evobrutinib groups. There was also no apparent effect of EVO dose received in the DBP on safety parameters in the OLE.

Conclusions

In a 60 week OLE period of a Phase II study, the safety of EVO was similar to that seen in the DBP. Overall, long-term EVO treatment was generally well tolerated in patients with relapsing MS.

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