Refractory EpilepsyPhase 2NCT04153175
Study to Assess Intracerebroventricular (ICV) Delivery of CT-010 in Subjects With Focal Seizures, With Temporal Lobe Onset With or Without Secondary Generalization
A Phase 2 study testing ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC) in people with Refractory Epilepsy, run by Cerebral Therapeutics LLC at 11 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 21 Aug 2020to 1 Mar 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -
- For a subject to be eligible for this study, he or she must meet ALL of the following criteria:
- Subject is male or female between the ages of 18 to 70 years old.
- Subject is considered an appropriate surgical candidate by the implanting Neurosurgeon.
- 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.
- In the opinion of the Investigator, subject has disabling seizures.
Show all 28Show fewer
- 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)
- 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.
- 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)
- 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.
- Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the Investigator, by the subject or caregiver.
- Subject understands study procedures and has voluntarily provided signed, informed consent in accordance with institutional and local regulatory requirements.
- 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:
- 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.
- Subject has any coagulopathy, ventricular anatomic distortion, or previous brain resection.
- 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.
- 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.
- Subject has had status epilepticus refractory to benzodiazepines and a second agent within one year prior to consent
- Subject is currently taking neuroleptic medication for behavior control.
- Subject has a clear brain anatomic structural related lesion which distorts the normal anatomy or interferes with CSF fluid flow.
- 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.
- Subject is currently implanted with an activated DBS, or RNS device used for treatment of a neurologic or psychiatric condition.
- 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.
- Subject has had more than 10 seizures in one day or more than 200 seizures in one month within last year.
- Subject has known allergy to citrate, citric acid, valproic acid, divalproex sodium, any components of CT-010, or Depacon®.
- 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.
- 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
Who cannot join
None listed.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
Australia7 sites
Mater Hospital Brisbane
Brisbane, New South Wales
RBWH
Brisbane, New South Wales
Royal Brisbane Medical Center
Brisbane, New South Wales
The Mater
Brisbane, New South Wales
SVHM
Melbourne, Victoria
The Alfred
Melbourne, Victoria
The Austin
Melbourne, Victoria
Israel4 sites
Hadassah Medical Center
Jerusalem
Sheba Medical Center
Ramat Gan
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Tel Aviv Sourasky Medical Center
Tel Aviv
About this study
Official 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
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 20 clinical centers will be enrolled.
Read the detailed description
Epilepsy patients that are refractory to oral anti-epileptic drug (AED) treatment have significantly higher mortality, higher morbidity, higher economic costs and diminished quality of life compared to those who suffer from epilepsy that can be adequately controlled with medical management. Current options for refractory patients include neurosurgical brain resection, responsive neurostimulation, and vagal nerve stimulation. None of these options is satisfactory due to the low applicability of surgery for patients with poorly localized or multifocal seizures and the limited success of currently available alternative treatment options.
In this study, patients with medically refractory focal epilepsy will be treated with intracerebroventricular (ICV) administration of CT-010, a reformulation of valproate, using an implantable drug pump system. This is a randomized, double-blind Phase 2 study evaluating the efficacy and safety of this therapy. Clinical assessments, adverse events (AEs), seizure diaries, concomitant medications, blood samples and cerebrospinal fluid (CSF) will be collected and reviewed at designated time points. Magnetic resonance imaging (MRI) and electroencephalography (EEG) will also be performed. Subjects will have their surgery, dose changes and pharmacokinetics performed in an inpatient setting.
Subjects will be enrolled based on Inclusion/Exclusion Criteria and undergo a 6-week baseline period confirming and establishing monthly seizure rate. Following the baseline period subjects will undergo system implant and a 1-month implant recovery period. Following successful implant and recovery subjects will be randomized to either active therapy or placebo for a 3-month blinded evaluation period. At the conclusion of the blinded evaluation period, subjects will roll into an Open Label Extension Period, CLN100P.02. Subjects that were randomized to placebo will receive active therapy during CLN100P.02.
- Conditions
- Refractory Epilepsy
- Being tested
- ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC), Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)Combination product
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of CT-010.
Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)Combination product
Subjects will be implanted with a drug delivery pump and catheters leading to the ICV space allowing delivery of a placebo (saline).
| Study group | Role | What they receive |
|---|---|---|
| CT-010 Active Therapy | Active comparator | 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. Receives: Combination Product: ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC) |
| Placebo | Placebo comparator | 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. Receives: Combination Product: Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 84 days
Secondary outcomes (5)
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.
Measured: 84 days
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.
Measured: 84 days
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.
Measured: 84 days
BDI
Evaluation of depression through the BDI questionnaire
Measured: 84 days
BAI
Evaluation of anxiety through the BAI questionnaire
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start21 Aug 2020
- Primary completion1 Mar 2024
- Study completion1 Mar 2024
Why it stopped: Company Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerebral Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04153175
- Sponsor's protocol ID
- CLN100P.01
- Status last verified
- Mar 2024
- First submitted
- 3 Nov 2019
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04153175
- Acronym / sponsor ID
- CLN100P.01
- Conditions
- Refractory Epilepsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company Decision
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Cerebral Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Aug 2020 (actual)
- Primary completion
- 1 Mar 2024 (actual)
- Study completion
- 1 Mar 2024 (actual)
- First posted
- 6 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 20 clinical centers will be enrolled.
Detailed description
Epilepsy patients that are refractory to oral anti-epileptic drug (AED) treatment have significantly higher mortality, higher morbidity, higher economic costs and diminished quality of life compared to those who suffer from epilepsy that can be adequately controlled with medical management. Current options for refractory patients include neurosurgical brain resection, responsive neurostimulation, and vagal nerve stimulation. None of these options is satisfactory due to the low applicability of surgery for patients with poorly localized or multifocal seizures and the limited success of currently available alternative treatment options.
In this study, patients with medically refractory focal epilepsy will be treated with intracerebroventricular (ICV) administration of CT-010, a reformulation of valproate, using an implantable drug pump system. This is a randomized, double-blind Phase 2 study evaluating the efficacy and safety of this therapy. Clinical assessments, adverse events (AEs), seizure diaries, concomitant medications, blood samples and cerebrospinal fluid (CSF) will be collected and reviewed at designated time points. Magnetic resonance imaging (MRI) and electroencephalography (EEG) will also be performed. Subjects will have their surgery, dose changes and pharmacokinetics performed in an inpatient setting.
Subjects will be enrolled based on Inclusion/Exclusion Criteria and undergo a 6-week baseline period confirming and establishing monthly seizure rate. Following the baseline period subjects will undergo system implant and a 1-month implant recovery period. Following successful implant and recovery subjects will be randomized to either active therapy or placebo for a 3-month blinded evaluation period. At the conclusion of the blinded evaluation period, subjects will roll into an Open Label Extension Period, CLN100P.02. Subjects that were randomized to placebo will receive active therapy during CLN100P.02.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CT-010 Active Therapy | Active comparator | Combination Product: ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC)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 | Placebo comparator | Combination Product: Placebo delivery via an implantable pump and a cranial port and dual lumen catheter (CIC)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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- -
- For a subject to be eligible for this study, he or she must meet ALL of the following criteria:
- Subject is male or female between the ages of 18 to 70 years old.
- Subject is considered an appropriate surgical candidate by the implanting Neurosurgeon.
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | CT-010 Active Therapy |
| 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). | Combination product | Placebo |
Primary outcome
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
Time frame: 84 days
5 secondary outcomes
Seizure Severity Questionnaire (SSQ)
Time frame: 84 days
QOLIE-10
Time frame: 84 days
Patient Global Impression of Change (PGIC)
Time frame: 84 days
BDI
Time frame: 84 days
BAI
Time frame: 84 days
Results and safety
The study was stopped early (reason given: Company Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ICV delivery of CT-010 via an implantable pump and a cranial port and dual lumen catheter (CIC) in people with Refractory Epilepsy, run by Cerebral Therapeutics LLC at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Australia, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Company Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.