Voronistat in Pediatric Patients With Drug Resistant Epilepsy

• Status: Unknown status
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Calgary
• Treatments: Vorinostat

Criteria

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