A Study of Lu AG06466 in Participants With Treatment Resistant Focal Epilepsy

Interventional, Randomized, Double-blind, Crossover, Placebo-controlled, Multiple-dose Lu AG06466 Phase 1 B Study in Patients With Focal Epilepsy Using EEG and PSG to Investigate Its Pharmacodynamic Effects on Prolonged Period of Inter- Icterical Spikes, Sleep and Neuroinflammation

The main purpose of this study is to investigate effects of Lu AG06466 on seizure activity after increasing daily doses during 4 weeks in participants with an implanted responsive neurostimulation system.

Study Overview

• Status: Terminated
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: Lu AG06466; Drug: Placebo

Detailed Description

This crossover study consists of 2 treatment periods, each of 29 days duration. On Day -1 of treatment period 1, eligible participants will be randomized (1:1) to a sequence of treatments (either Lu AG06466-placebo or placebo-Lu AG06466).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• The participant must have had the responsive neurostimulation system (RNS®) System implanted for more than 1 year and medically intractable focal onset epileptic seizures (history of persistent seizures refractory to 2 or more anti-epileptic drugs [AEDs]), with seizures from all foci represented in the implanted RNS electrodes.
• The participant is required to have a continuous period of at least 2 months prior to the Screening Visit with constant RNS stimulation settings as well as stable AED (that is, 60 days with no dose adjustments of more than 25%) as determined by medical history and the Patient Data Management System (PDMS). There must be at least 24 recorded long episodes available for review since last change of RNS detection setting.
• The participant is required to have approximately 7 or more long episodes per week, as assessed as an average over the last 2 months prior to the Screening Visit.
• The participant is required to have a demonstrated history of compliance with RNS scanning and uploading procedure in the past year (less than 20% missing long episode counts on the PDMS).

Key Exclusion Criteria:

• The participant has the RNS System implanted in other regions than the epileptic foci such as the thalamus.
• The participant has a RNS System with anticipated generator change in the coming 6 months.
• The participant has a cyclic pattern of long episodes in the last 2 months prior to the Screening Visit which exhibits, in the opinion of the investigator: a period of more than 3 weeks; and peak-to-trough differences of long episodes of more than half the peak level.
• The participant has or has had any clinically significant immunological, cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological, haematological, dermatological, venereal, neurological (apart from epileptic diagnosis), or psychiatric disease or other major disorder, which in opinion of the investigator may influence efficacy or safety aspects in the study.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: Lu AG06466-Placebo; Participants will receive Lu AG06466 capsules once daily (QD) at a low dose for 4 days (Days 1 to 4), medium dose for 4 days (Days 5 to 8), and high dose for 21 days (Days 9 to 29) in treatment period 1. Participants will receive matching placebo capsules from Day 1 to Day 29 in treatment period 2. Each treatment period will be separated by a washout period of 7 to 11 days.	Drug: Lu AG06466; Lu AG06466 - capsule; Drug: Placebo; Placebo - capsule
Experimental: Sequence 2: Placebo-Lu AG06466; Participants will receive matching placebo capsules QD from Day 1 to Day 29 in treatment period 1. Participants will receive Lu AG06466 capsules QD at a low dose for 4 days (Days 1 to 4), medium dose for 4 days (Days 5 to 8), and high dose for 21 days (Days 9 to 29) in treatment period 2. Each treatment period will be separated by a washout period of 7 to 11 days.	Drug: Lu AG06466; Lu AG06466 - capsule; Drug: Placebo; Placebo - capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of "Long Episodes" (Electrocorticographic [ECoG] Seizures)	"Long Episodes" are abnormal events detected by the neurostimulator that do not return to baseline ECoG activity within a predefined period of time, typically 30 to 60 seconds. These often correspond to ECoG seizures.	Baseline (Day -1) up to Day 29 of each treatment period

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2021
• Primary Completion (Actual): April 14, 2022
• Study Completion (Actual): April 14, 2022

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial
• Other Study ID Numbers: 19367A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No