Refractory EpilepsyPhase 2NCT03894826
Voronistat in Pediatric Patients With Drug Resistant Epilepsy
A Phase 2 study testing Vorinostat 100 MG in people with Refractory Epilepsy, run by University of Calgary at 1 site in Canada.
Trial summary
The study evaluates the safety, tolerability, and efficacy of Vorinostat in addition to standard of care anti-epileptic drugs in pediatric patients with medically refractory epilepsy. All participants entering the treatment phase will receive Vorinostat. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- Vorinostat 100 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 10 Dec 2018to Oct 2020
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Males or females aged 2 - 17 years (inclusive)
- Medically intractable epilepsy, defined as having failed at least 2 standard anti-seizures therapies and experiencing at least 3 motor seizures per week, separated by at least 24 hours that are quantifiable by observation (e.g. discrete episodes of motor activity). Participants experiencing other seizure types in addition to motor seizures may also be enrolled but must meet the minimal requirement for motor seizures.
- Ability and willingness of family and/or caregiver (when appropriate) to give written informed consent and to comply with requirement of the study
- Adequate bone marrow function (defined as an absolute neutrophil count (ANC) of > 2 x 109/L; platelet count of > 150 x 109/L; hemoglobin of > 110 g/L [3-11 years], > 120 g/L [females 12 years or over], > 125 g/L [males 12-14 years], > 137 g/L [males 15 years or older])
- Adequate renal function (defined as serum creatinine < 1.5X age-adjusted upper limit of normal [ULN], or glomerular filtration rate ≥ 70 mL/min/1.73 m2)
- Adequate hepatic function (defined as total bilirubin <1.5 times ULN, and alanine aminotransferase [ALT] and aspartate transaminase [AST] < 3 times ULN, and albumin >33 g/L)
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- Corrected QT (QTc) interval of < 450 msec
- Prothrombin time (PTT) < 1.5 ULN/International Normalized Ratio (INR) < 1.5 ULN
- Participants on corticosteroids must be taking a stable or decreasing dose for at least 7 days prior to enrollment
Who cannot join
- Treatment with valproic acid or other HDACi class drugs within at least the last 3 months at time of screening
- Enzyme-inducing AEDs (including oxcarbazepine (Trileptal), phenobarbital, phenytoin (Dilantin), topiramate (Topamax)
- Coumarin-derivative anti-coagulants
- Participants being considered for surgery for management of seizures during screening or who will be receiving surgery during for management of seizures during study period (includes all neurosurgery for the management of seizures or device implantation for the management of seizures)
- Neurosurgery within the past 12 months
- Use of Vagus Nerve Stimulator (VNS) where settings have not been stable for at least 6 months
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- Planned surgery or other invasive medical treatment during screening of during treatment period
- Hypokalemia or hypomagnesemia
- Participants starting or currently on any neurometabolic diet (including but not limited to ketogenic diet; medium-chain triglyceride diet; modified Atkins diet; low glycemic index diet) during study
- History of non-catheter related deep venous thrombosis
- Pleural effusion
- Malignancy within the past 5 years.
- Any serious medical condition that according to the investigator could interfere with the conduct of the study
- Serious comorbid disease in which the life expectancy of the patient is shorter than the duration of the trial
- Unwillingness or inability to comply with study requirements
- Positive pregnancy test, lactating females or heterosexually active participants not willing to use highly effective methods of contraception
- Participation in any clinical trial with an investigational drug, or therapy not approved by Health Canada, within one month prior to screening
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B6A8
Jong Rho, MD, 403-955-2296, jong.rho@ahs.ca
Sabrina D'Alfonso, MSc, 403-955-2745, sabrina.d'alfonso@ahs.ca
About this study
Official title: A Phase 2 Clinical Trial Testing the Safety and Efficacy of Voronistat in Pediatric Patients With Drug Resistant Epilepsy
The study evaluates the safety, tolerability, and efficacy of Vorinostat in addition to standard of care anti-epileptic drugs in pediatric patients with medically refractory epilepsy. All participants entering the treatment phase will receive Vorinostat.
Read the detailed description
Vorinostat is a potent inhibitor of histone deacetylases (HDAC). HDACs catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. Valproic acid, a broad anti-epileptic drug, commonly used as first line treatment in epilepsy, has also been shown to inhibit HDAC activity .
It is it is anticipated that Vorinostat in a population of pediatric patients with epilepsy will be well-tolerated, similar to that seen with valproic acid and other normally prescribed anti-epileptic drugs.
Participants consenting to participate will enter a 4-week screening period to ensure eligibility. Eligible participants will then enter the 6-week treatment phase. Participants will be seen for a final Safety Follow-up visit 6 weeks after end of treatment. Participants who are enrolled and complete all study procedures will be in the study for a total of 16 weeks.
- Conditions
- Refractory Epilepsy
- Being tested
- Vorinostat 100 MG
- Keywords
- PEDIATRIC
- 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.
Vorinostat 100 MGDrug
Also called ZOLINZA
Vorinostat administered by mouth, once daily at a dose of 230 mg/m2/day for a total of 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| TREATMENT | Experimental | Participants will be administered 230 mg/m2/day of oral Vorinostat [100 mg tablets] in addition to standard of care anti-seizure medication for a duration of 6 weeks. Receives: Drug: Vorinostat 100 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
The number of treatment emergent adverse events will be tabulated at each time point: adverse events, serious adverse events, and discontinuations due to adverse events.
Measured: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
Incidence of Drug Discontinuations due to Adverse Drug Reaction
The number of participants with drug discontinuations due to Adverse Drug Reaction will be tabulated at each time point: adverse events, serious adverse events, and discontinuations due to adverse events.
Measured: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
Secondary outcomes (2)
Proportion of participants who have at least a 50% reduction in seizures from baseline
Treatment response will be evaluated by calculating the proportion of response of participants who demonstrate a 50% reduction rate or greater at 6 weeks as compared to baseline.
Measured: 42 days post drug initiation; change from baseline
Change in seizure status at each time point.
Seizure status will be tabulated 14 days following drug initiation; 30 days following drug initiation; 42 days following drug initiation; and 42 days following drug discontinuation. Seizure status will be defined as: significant response (at least 50% reduction in seizure frequency as compared to baseline, or no seizures while on medication; partial response (25% - 49% reduction in seizure frequency as compared to baseline); no change, (0 - 24% reduction in seizure frequency as compared to baseline); and worsening (increase in seizure frequency as compared to baseline).
Measured: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2019
- Study start10 Dec 2018
- Primary completionApr 2020 (estimated)
- Study completionOct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jong Rho, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03894826
- Sponsor's protocol ID
- VOR-17-2471
- Status last verified
- Mar 2019
- First submitted
- 13 Sep 2018
- Last updated
- 29 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared with other researchers.
Publications
Ibhazehiebo K, Gavrilovici C, de la Hoz CL, Ma SC, Rehak R, Kaushik G, Meza Santoscoy PL, Scott L, Nath N, Kim DY, Rho JM, Kurrasch DM. A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target. Brain. 2018 Mar 1;141(3):744-761. doi: 10.1093/brain/awx364.
PubMed 29373639Garcia AA, Koperniku A, Ferreira JCB, Mochly-Rosen D. Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives. Trends Pharmacol Sci. 2021 Oct;42(10):829-844. doi: 10.1016/j.tips.2021.07.002. Epub 2021 Aug 10.
PubMed 34389161
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Clinical Trial Testing the Safety and Efficacy of Voronistat in Pediatric Patients With Drug Resistant Epilepsy
- ClinicalTrials.gov ID
- NCT03894826
- Acronym / sponsor ID
- VOR-17-2471
- Conditions
- Refractory Epilepsy
- Keywords
- PEDIATRIC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 10 Dec 2018 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Oct 2020 (estimated)
- First posted
- 29 Mar 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.
The study evaluates the safety, tolerability, and efficacy of Vorinostat in addition to standard of care anti-epileptic drugs in pediatric patients with medically refractory epilepsy. All participants entering the treatment phase will receive Vorinostat.
Detailed description
Vorinostat is a potent inhibitor of histone deacetylases (HDAC). HDACs catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. Valproic acid, a broad anti-epileptic drug, commonly used as first line treatment in epilepsy, has also been shown to inhibit HDAC activity .
It is it is anticipated that Vorinostat in a population of pediatric patients with epilepsy will be well-tolerated, similar to that seen with valproic acid and other normally prescribed anti-epileptic drugs.
Participants consenting to participate will enter a 4-week screening period to ensure eligibility. Eligible participants will then enter the 6-week treatment phase. Participants will be seen for a final Safety Follow-up visit 6 weeks after end of treatment. Participants who are enrolled and complete all study procedures will be in the study for a total of 16 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TREATMENT | Experimental | Drug: Vorinostat 100 MGParticipants will be administered 230 mg/m2/day of oral Vorinostat [100 mg tablets] in addition to standard of care anti-seizure medication for a duration of 6 weeks. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Males or females aged 2 - 17 years (inclusive)
- Medically intractable epilepsy, defined as having failed at least 2 standard anti-seizures therapies and experiencing at least 3 motor seizures per week, separated by at least 24 hours that are quantifiable by observation (e.g. discrete episodes of motor activity). Participants experiencing other seizure types in addition to motor seizures may also be enrolled but must meet the minimal requirement for motor seizures.
- Ability and willingness of family and/or caregiver (when appropriate) to give written informed consent and to comply with requirement of the study
- Adequate bone marrow function (defined as an absolute neutrophil count (ANC) of > 2 x 109/L; platelet count of > 150 x 109/L; hemoglobin of > 110 g/L [3-11 years], > 120 g/L [females 12 years or over], > 125 g/L [males 12-14 years], > 137 g/L [males 15 years or older])
- Adequate renal function (defined as serum creatinine < 1.5X age-adjusted upper limit of normal [ULN], or glomerular filtration rate ≥ 70 mL/min/1.73 m2)
Key exclusion criteria (17 listed)
- Treatment with valproic acid or other HDACi class drugs within at least the last 3 months at time of screening
- Enzyme-inducing AEDs (including oxcarbazepine (Trileptal), phenobarbital, phenytoin (Dilantin), topiramate (Topamax)
- Coumarin-derivative anti-coagulants
- Participants being considered for surgery for management of seizures during screening or who will be receiving surgery during for management of seizures during study period (includes all neurosurgery for the management of seizures or device implantation for the management of seizures)
- Neurosurgery within the past 12 months
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 |
|---|---|---|
| Vorinostat 100 MGAlso: ZOLINZAVorinostat administered by mouth, once daily at a dose of 230 mg/m2/day for a total of 6 weeks | Drug | TREATMENT |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
The number of treatment emergent adverse events will be tabulated at each time point: adverse events, serious adverse events, and discontinuations due to adverse events.
Incidence of Drug Discontinuations due to Adverse Drug Reaction
Time frame: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
The number of participants with drug discontinuations due to Adverse Drug Reaction will be tabulated at each time point: adverse events, serious adverse events, and discontinuations due to adverse events.
2 secondary outcomes
Proportion of participants who have at least a 50% reduction in seizures from baseline
Time frame: 42 days post drug initiation; change from baseline
Change in seizure status at each time point.
Time frame: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Results publication: PubMed 29373639Ibhazehiebo K, Gavrilovici C, de la Hoz CL, Ma SC, Rehak R, Kaushik G, Meza Santoscoy PL, Scott L, Nath N, Kim DY, Rho JM, Kurrasch DM. A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target. Brain. 2018 Mar 1;141(3):744-761. doi: 10.1093/brain/awx364.
- Derived from this study: PubMed 34389161Garcia AA, Koperniku A, Ferreira JCB, Mochly-Rosen D. Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives. Trends Pharmacol Sci. 2021 Oct;42(10):829-844. doi: 10.1016/j.tips.2021.07.002. Epub 2021 Aug 10.
- Individual participant dataSharing planned: No. IPD will not be shared with other researchers.
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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.
Jong Rho, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vorinostat 100 MG in people with Refractory Epilepsy, run by University of Calgary at 1 site in Canada.
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 9 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 29 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sabrina D'Alfonso, MSc (403-955-2745, sabrina.d'alfonso@ahs.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03894826, which also lists 2 linked publications.
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 29 Mar 2019.