We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04153175




Registration number
NCT04153175
Ethics application status
Date submitted
3/11/2019
Date registered
6/11/2019
Date last updated
12/01/2021

Titles & IDs
Public title
Study to Assess Intracerebroventricular (ICV) Delivery of CT-010 in Subjects With Focal Seizures, With Temporal Lobe Onset With or Without Secondary Generalization
Scientific title
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Assess Intracerebroventricular (ICV) Delivery of CT-010 Via an Implantable Pump and a Cranial Port and Double Lumen Catheter (ICVRX) in Subjects With Focal Seizures, With Temporal Lobe Onset With or Without Secondary Generalization
Secondary ID [1] 0 0
CLN100P.01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Refractory Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)
Combination Product - Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)

Active Comparator: CT-010 Active Therapy - Subjects in the active comparator arm will have been randomized to receive active therapy through the implanted drug delivery system through the 3-month blinded period.

Placebo Comparator: Placebo - Subjects in the placebo comparator arm will have been randomized to receive placebo therapy through the implanted drug delivery system for the 3-month blinded period.


Combination Product: ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of CT-010.

Combination Product: Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of a placebo (saline).

Intervention code [1] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Median frequency of total monthly seizures during the Primary Evaluation Period as compared to the Baseline Period as well as a comparison of this Baseline Period/Primary Evaluation Period ratio for the active vs. placebo treatment groups
Timepoint [1] 0 0
84 days
Secondary outcome [1] 0 0
Seizure Severity Questionnaire (SSQ) - Evaluation of change in seizure severity during the blinded period by evaluating any change in the SSQ scores between baseline and Day 84 of blinded period where a lower score is an improvement in condition.
Timepoint [1] 0 0
84 days
Secondary outcome [2] 0 0
QOLIE-10 - Evaluation of change in quality of life during the blinded period by evaluating change in QOLIE-10 scores between baseline and 84-day evaluations.
Timepoint [2] 0 0
84 days
Secondary outcome [3] 0 0
Patient Global Impression of Change (PGIC) - Evaluation of subjects impression of therapy efficacy through the PGIC questionnaire at the conclusion of the blinded period. Scale is a single question with a score of 1-7 with a higher score representing a greater improvement in condition. The score is also captured as a VAS of 1-10 again with a higher score representing a greater improvement in condition.
Timepoint [3] 0 0
84 days
Secondary outcome [4] 0 0
BDI - Evaluation of depression through the BDI questionnaire
Timepoint [4] 0 0
84 days
Secondary outcome [5] 0 0
BAI - Evaluation of anxiety through the BAI questionnaire
Timepoint [5] 0 0
84 days

Eligibility
Key inclusion criteria
Inclusion/
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-

For a subject to be eligible for this study, he or she must meet ALL of the following
criteria:

1. Subject is male or female between the ages of 18 to 70 years old.

2. Subject is considered an appropriate surgical candidate by the implanting
Neurosurgeon.

3. Subject has had confirmed refractory epilepsy for a minimum of 2 years, with
unilateral or bilateral temporal lobe involvement with no more than 2 known
extratemporal foci.

4. In the opinion of the Investigator, subject has disabling seizures.

5. Subject has had at least one seizure recorded by EEG or video EEG or invasive
monitoring within the past 3 years consistent with focal temporal lobe seizures (a
normal interictal EEG is consistent with focal seizures)

6. Subject has not achieved effective results previously from at least 3 AEDs in single
or combination. An AED may be counted as failed medication if subject has been on it
for at least 3-months and is still refractory.

7. Subject failed to obtain an adequate intake of oral valproate of at least 1,000 mgs a
day and/or to achieve serum level of at least 60 µg/mL or in the opinion of the
Investigator is not a candidate for oral valproate (including subject preference)

8. Per medical history, for the 3 months before informed consent an average of six or
more disabling focal seizures of temporal lobe onset, with or without secondary
generalization, per month.

9. Subject has seizures that are distinct, stereotypical events that can be reliably
counted, in the opinion of the Investigator, by the subject or caregiver.

10. Subject understands study procedures and has voluntarily provided signed, informed
consent in accordance with institutional and local regulatory requirements.

11. Subject agrees to maintain the diary for the duration of the study alone or with the
assistance of a competent individual.

Subjects must NOT meet any of the following Exclusion criteria to be eligible for
enrollment:

1. Subject has any neurologic or medical disease that is likely to progress over the
course of the study and/or would interfere with the study.

2. Subject has any coagulopathy, ventricular anatomic distortion, or previous brain
resection.

3. Subject has history, within 12 months prior to consent, of repetitive seizures that
cannot be counted with confidence by the subject or competent adult/caregiver.

4. Subject has history of psychogenic nonepileptic seizures or seizures secondary to
illicit drug or alcohol use, neoplasia, active central nervous system infection,
demyelinating disease, degenerative neurological disease, progressive CNS disease or
metabolic illness.

5. Subject has had status epilepticus refractory to benzodiazepines and a second agent
within one year prior to consent

6. Subject is currently taking neuroleptic medication for behavior control.

7. Subject has a clear brain anatomic structural related lesion which distorts the normal
anatomy or interferes with CSF fluid flow.

8. Subject has required (in addition to low dose stable use of benzodiazepines as part of
antiepileptic regimen), in the 3 months prior to consent, benzodiazepine use more than
5 times per month for rescue seizure control. One use is defined as taking up to 3
doses in a 24-hour period.

9. Subject is currently implanted with an activated DBS, or RNS device used for treatment
of a neurologic or psychiatric condition.

10. Subject currently has VNS and the VNS stimulation parameters are not stable. Stable
shall be defined such that the stimulation parameters have not been changed in the
last 3 months or the patient/designee is able to report "magnet swipe" during the same
time period. The Investigator believes that the continued stable parameters can be
maintained through the Primary Evaluation Period.

11. Subject has had more than 10 seizures in one day or more than 200 seizures in one
month within last year.

12. Subject has known allergy to citrate, citric acid, valproic acid, divalproex sodium,
any components of CT-010, or Depacon®.

13. Subject has unstable depression being treated with more than 1 antidepressant
medication or has current evidence of or history within the past 2 years of DSM-IV
criteria for any major psychiatric disorder including psychosis, major depression,
bipolar disorder, and has had a suicide attempt within the previous five years. Also
excluded are subjects with a history of prolonged postictal psychosis or psychosis or
depression secondary to a discontinued AED.

14. In the opinion of the Investigator, the subject has a clinically significant or
unstable medical condition (e.g., uncontrolled diabetes or CHF) or a progressive CNS
disease that would limit the subject's entry into the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
SVHM - Melbourne
Recruitment hospital [2] 0 0
The Alfred - Melbourne
Recruitment hospital [3] 0 0
The Austin - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Ramat Gan

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cerebral Therapeutics LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 2 double-blind, randomized, placebo-controlled study to assess the safety and
efficacy of ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen
catheter (CIC) in subjects with focal seizures, with temporal lobe onset with or without
secondary generalization. Up to 70 subjects will be enrolled. Eligible subjects will be
randomized in a 1:1 ratio to either CT-010 or placebo treatment. Up to 14 clinical centers
will be enrolled.
Trial website
https://clinicaltrials.gov/show/NCT04153175
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eric Distad
Address 0 0
Country 0 0
Phone 0 0
+1 3038852610
Fax 0 0
Email 0 0
distad.e@cerebraltherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04153175