CENOR Study
Research type
Research Study
Full title
Retrospective study on the use of CENOBAMATE as adjunctive treatment in a cohort of patients suffering from epilepsy with Focal Onset Seizure (FOS) and enrolled into the Early Access Program (EAP) in Germany, France and UK
IRAS ID
322489
Contact name
Rhys Thomas
Contact email
Sponsor organisation
Angelini Pharma SpA
Clinicaltrials.gov Identifier
169(A)MD21350, Clinical Investigation Plan
Duration of Study in the UK
0 years, 6 months, days
Research summary
Research Summary
The CENOR study is a retrospective, cohort study based on the data collected from the Early Access Program (EAP) that was ran in the UK, France and Germany from September 2020- September 2022 that focuses on data from people suffering from epilepsy with Focal Onset Seizure (FOS) and have been treated with cenobamate as adjunctive Anti-Seizure Medication (ASM) during the EAP. The main question from the study is to understand and confirm the and tolerability of Cenobamate from real-world data in a large series of patients treated with Cenobamate as adjunctive anti-seizure medication. Eligible patients have to be 18years or older and a total of 26 sites across the EU (UK, Germany, France) will be opened for the study with the UK sites being NHS organisations specialising in neurological issues such as epilepsy. The study will run for 6months in total.
Summary of Results
The study primary efficacy endpoint was the responder rate (Responders+Seizure Free) after 3 months of maintenance phase: this figure was 40.82% both in the FAS (Full analysis set) and in the mITT (Modified Intent- to-Treat) (all seizure types were collected in patients with FOS (Focal -Onset Epilepsy) with or without secondary generalization), when calculated on patients with data available (n=49). A trend towards an increase was shown in the Seizure Free rate, from 6.3% to 13.8% at 1 and 3 months from CNB start (Cenobamate), to 14.3% and 26.1% at 3 and 6 month-maintenance, respectively. In our study, the percentage median seizure reduction was 54.2% at 3 months of CNB start, consistent with results from the above real-world study (Villaneuva et al 2023), where the percentage mean seizure reduction was 55.1 % at the same time point.
Since patients with verifiable seizure data decreased significantly (109 patients with seizure data available at 3 month of CNB start, 49 at 3 months of CNB maintenance, 23 at 6 months of CNB maintenance, 5 patients at 12 months of CNB maintenance), it is difficult to state if the increase in absolute and relative number of responders later in the study was related to study exit of non-responders. Nevertheless, the percentage of responder/seizure free patients, also increased between 1 to 3 mths from CNB start, where the number of patients with seizure data available increases: from 29.7% (19/64) to 52.3% (57/109). Moreover, most of the missing data at each time point was due to cessation of data collection at EAP (Early Access Program) end, not to CNB discontinuation for safety reason or lack or efficacy (in only 2 cases the AE (Adverse Event) “increase in seizure frequency” was reported). At 3 months after maintenance start, the mean (range) dose was 210.9 (50; 400), at 6 months it was 242.0 (100- 400) and at 12 months 225.0 (200-300); at these time points the median was 200 mg.
After 3 months of maintenance, a subset of patients reported a benefit with doses of CNB <200 mg per day: of 7 patients with seizure data available at this dosage, 4 were responders; at 6 months, both patients at low dosage were responders. At the 12-month time point, only dosages ≥ 200 mg/day were reported.
Notably, out of 314 AEs, 14 (4.46%) led to discontinuation of concomitant treatments, 78 (24.84%) to dose modifications.
Overall, 38/298 (SS) patients (12.75%) discontinued CNB permanently, in equal rate during titration and maintenance phases. Due to the retrospective nature, it was not always possible to establish the correlation between adverse events and discontinuation, except for 9/38 cases, where no ADR (Adverse Drug Reaction) related to CNB occurred and 9 cases (3.02% of SS (safety set)) where the safety reason for discontinuation was clearly stated in the clinical chart.
In conclusion, the safety profile of CNB from this real-world study confirms the findings from clinical trials; nature and frequency of ADRs reported is in line with the product SPC. Allergic reactions only occurred in 7/298 subjects with a rate of 2.3% (described as ‘uncommon’ per SPC (Summary of Product Characteristics), i.e < 1%); moreover, this rate was consistent with the cutaneous event rate in a similar real-world study on EAP, from Villanueva et al. (2.9%). The unique unlisted SADR was the report of urinary retention in a patient with neurological bladder.REC name
Wales REC 3
REC reference
22/WA/0358
Date of REC Opinion
14 Dec 2022
REC opinion
Favourable Opinion