Voronistat in Pediatric Patients With Drug Resistant Epilepsy

NCT03894826 | Unknown Phase 2

• 1 other identifier: VOR-17-2471
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Refractory Epilepsy

Keywords

PEDIATRIC

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  42 days post drug initiation; change from baseline

• Change in seizure status at each time point.

  14 days post drug initiation; 30 days post drug initiation; 42 days post drug initiation; 42 days following drug discontinuation

Study Arms (1)

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.

Drug: Vorinostat 100 MG

Interventions

Vorinostat 100 MG DRUG

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

Also known as: ZOLINZA

TREATMENT

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Alberta Children's Hospital

Calgary, Alberta, T3B6A8, Canada

RECRUITING

Related Publications (2)

• 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.

  PMID: 29373639 RESULT

• 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.

  PMID: 34389161 DERIVED

MeSH Terms

Conditions

Drug Resistant Epilepsy

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Jong Rho, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sabrina D'Alfonso, MSc

CONTACT

403-955-2745; sabrina.d'alfonso@ahs.ca

Jong Rho, MD

CONTACT

403-955-2296; jong.rho@ahs.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: March 29, 2019
• Study Start: December 10, 2018
• Primary Completion: April 1, 2020
• Study Completion: October 1, 2020
• Last Updated: March 29, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)