Voronistat in Pediatric Patients With Drug Resistant Epilepsy

NCT ID: NCT03894826

Last Updated: 2019-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-10

Study Completion Date

2020-10-31

Brief Summary

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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

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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

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Refractory Epilepsy

Keywords

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PEDIATRIC

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TREATMENT

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.

Group Type EXPERIMENTAL

Vorinostat 100 MG

Intervention Type DRUG

Vorinostat administered by mouth, once daily at a dose of 230 mg/m2/day for a total of 6 weeks

Interventions

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Vorinostat 100 MG

Vorinostat administered by mouth, once daily at a dose of 230 mg/m2/day for a total of 6 weeks

Intervention Type DRUG

Other Intervention Names

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ZOLINZA

Eligibility Criteria

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Inclusion Criteria

1. Males or females aged 2 - 17 years (inclusive)
2. 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.
3. Ability and willingness of family and/or caregiver (when appropriate) to give written informed consent and to comply with requirement of the study
4. 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 \[males 15 years or older\])
5. 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)
6. 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)
7. Corrected QT (QTc) interval of \< 450 msec
8. Prothrombin time (PTT) \< 1.5 ULN/International Normalized Ratio (INR) \< 1.5 ULN
9. Participants on corticosteroids must be taking a stable or decreasing dose for at least 7 days prior to enrollment

Exclusion Criteria

1. Treatment with valproic acid or other HDACi class drugs within at least the last 3 months at time of screening
2. Enzyme-inducing AEDs (including oxcarbazepine (Trileptal), phenobarbital, phenytoin (Dilantin), topiramate (Topamax)
3. Coumarin-derivative anti-coagulants
4. 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)
5. Neurosurgery within the past 12 months
6. Use of Vagus Nerve Stimulator (VNS) where settings have not been stable for at least 6 months
7. Planned surgery or other invasive medical treatment during screening of during treatment period
8. Hypokalemia or hypomagnesemia
9. 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
10. History of non-catheter related deep venous thrombosis
11. Pleural effusion
12. Malignancy within the past 5 years.
13. Any serious medical condition that according to the investigator could interfere with the conduct of the study
14. Serious comorbid disease in which the life expectancy of the patient is shorter than the duration of the trial
15. Unwillingness or inability to comply with study requirements
16. Positive pregnancy test, lactating females or heterosexually active participants not willing to use highly effective methods of contraception
17. Participation in any clinical trial with an investigational drug, or therapy not approved by Health Canada, within one month prior to screening
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Calgary

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jong Rho, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

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Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Sabrina D'Alfonso, MSc

Role: CONTACT

Phone: 403-955-2745

Email: sabrina.d'[email protected]

Jong Rho, MD

Role: CONTACT

Phone: 403-955-2296

Email: [email protected]

Facility Contacts

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Jong Rho, MD

Role: primary

Sabrina D'Alfonso, MSc

Role: backup

References

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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.

Reference Type RESULT
PMID: 29373639 (View on PubMed)

Garcia 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.

Reference Type DERIVED
PMID: 34389161 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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VOR-17-2471

Identifier Type: -

Identifier Source: org_study_id