Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy

Inclusion Criteria:

1. Clinical or mutational diagnosis of TSC consistent with:

2. Molecular confirmation of a pathogenic mutation in TSC1 or TSC2. A pathogenicmutation is defined as a mutation that clearly prevents protein synthesisand/or inactivates the function of the TSC1 or TSC2 proteins (eg, nonsensemutation or frameshift mutations, large genomic deletions) or is a missensemutation whose effect on protein function has been established by functionalassessment. The Principal investigator (PI) or designee must review the resultsof the genetic analysis and confirm that the causal relationship to theepilepsy syndrome is likely. OR

3. Clinical diagnosis of definite TSC which includes 2 major features or 1 majorfeature with ≥ 2 minor features.

4. Male or female participants aged 1 through 65 years, inclusive. For Europe (EU),Middle East and North Africa (MENA), and Oceania (OC) Male or Female participantsaged 2 through 65 years, inclusive.

5. Participant/parent(s) or LAR(s) willing to give written informed consent/assent,after being properly informed of the nature and risks of the study and prior toengaging in any study related procedures. If the participant is not qualified norable to provide written informed consent based on age, developmental stage,intellectual capacity, or other factors, parent(s)/LAR(s) must provide consent forstudy participation, if appropriate.

6. Failure to control seizures despite appropriate trial of 2 or more Anti-seizuremedication (ASMs) at therapeutic doses and for adequate duration of treatment per PIjudgment.

7. Participants should be on a stable regimen of ASMs (including moderate or stronginducer or inhibitor ASM eg, carbamazepine, phenytoin, etc.) at therapeutic dosesfor ≥ 28 days prior to the screening visit, and without a foreseeable change indosing for the duration of the study. (Note: Minor dose adjustment to addresstolerability and safety events may be allowed on case-by-case basis and it should bediscussed with the study medical monitor.)

8. A history of at least 8 countable seizures per month in the 2 months prior toscreening with no more than 1 seizure free week in each month. This includesseizures of any kind.

9. Have at least 8 primary endpoint seizures in the first 28 days following thescreening visit. The primary endpoint seizure types are defined as the following:

10. focal motor seizures without impairment of consciousness or awareness

11. focal seizures with impairment of consciousness or awareness with motorfeatures

12. focal seizures evolving to bilateral, tonic-clonic seizures

13. generalized motor seizures including tonic-clonic, bilateral tonic, bilateralclonic, or atonic/drop seizures. Seizures that do not count towards the primary endpoint include:

14. Focal or generalized nonmotor seizures (eg, absence seizures or focal nonmotorseizures with or without impairment of awareness)

15. Infantile or epileptic spasms

16. Myoclonic seizures.

17. Participants with surgically implanted vagal nerve stimulator (VNS) will be allowedto enter the study provided that all of the following conditions are met:

18. The VNS has been in place for ≥ 6 months prior to the screening visit.

19. The settings must have remained constant for 3 months prior to the screeningvisit and are expected to remain constant throughout the study.

20. The battery is expected to last for the duration of the study.

21. Parent(s)/caregiver(s)/LAR(s) or the participant, as appropriate, is (are) willingand able to maintain an accurate and complete daily seizure eDiary for the durationof the study.

22. Willing and able to take IP (suspension) as directed with food (TID).

23. Women of childbearing potential (WOCBP) must be using a medically acceptable methodof birth control and have a negative quantitative serum beta-human chorionic growthhormone (β-HCG) test collected at the initial screening and Baselinevisits.Childbearing potential is defined as a female who is biologically capable ofbecoming pregnant. A medically acceptable method of birth control includesintrauterine devices (that have been in place for at least 1 month prior to thescreening visit), hormonal contraceptives (eg, combined oral contraceptives, patch,vaginal ring, injectables, and implants), and surgical sterilization (such asoophorectomy or tubal ligation. When used consistently and correctly, "double-barrier" methods of contraception can be used as an effective alternative tohighly effective contraception methods. Contraceptive measures such as Plan B™, soldfor emergency use after unprotected sex, are not acceptable methods for routine use.

24. Male participants must agree to use highly effective contraceptive methods duringthe study and for 30 days after the last dose of IP. Highly effective methods ofcontraception include surgical sterilization (such as a vasectomy) and adequate "double-barrier" methods.

Exclusion Criteria:

1. Previous exposure to GNX.

2. Pregnant or breastfeeding.

3. Participants who have been taking felbamate for less than 1 year prior to screening.

4. Participants taking cannabidiol (CBD) preparations other than Epidiolex.

5. A positive result on plasma drug screen for CBD or tetrahydrocannabinol (THC) atVisit 1 (screening), with the exception of results that are fully explained byEpidiolex, which can be adjusted by the investigator in the event of any Adverseevents (AEs).

6. Concurrent use of adrenocorticotropic hormone (ACTH), prednisone or otherglucocorticoid is not permitted, nor use of the strong inducers of cytochrome P450 3A4 (CYP3A4), rifampin and St John's Wort. Participants on ACTH, prednisone, orother systemically (non-inhaled or topical) administered steroids should be off theproduct > 28 days prior to screening. Rifampin and St John's Wort must bediscontinued at least 28 days before Visit 2, study drug initiation. Note:

7. Use of concomitant intranasal or pro re nata (PRN) topical steroids fordermatologic reactions and allergic rhinitis are allowed during the study.

8. This exclusion criterion does not prohibit the use of approved ASMs.

9. Changes in any chronic medications within the 4 weeks prior to the screening visit.All chronic concomitant medications must be relatively stable in dose for at least 4weeks prior to the screening visit unless otherwise noted. Small dose adjustment tomanage tolerability and safety events is permitted and should be discussed with thestudy medical monitor.

10. Participants who have epilepsy surgery planned during the study or who haveundergone surgery for epilepsy within the 6 months prior to screening.

11. An active central nervous system (CNS) infection, demyelinating disease,degenerative neurological disease, or CNS disease deemed progressive as evaluated bybrain magnetic resonance imaging (MRI). This includes tumor growth which in theopinion of the investigator could affect primary endpoint seizure control.

12. Any disease or condition (medical or surgical; other than TSC) at the screeningvisit that might compromise the hematologic, cardiovascular (including any cardiacconduction defect), pulmonary, renal, gastrointestinal, or hepatic systems; or otherconditions that might interfere with the absorption, distribution, metabolism, orexcretion of the IP, or would place the participant at increased risk or interferewith the assessment of safety/efficacy. This may include any illness in the past 4weeks which in the opinion of the investigator may affect seizure frequency.

13. Hepatic impairment sufficient to affect participant safety, or an aspartateaminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) or alanineaminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) > 3 × the upperlimit of normal (ULN) at screening or Baseline visits and confirmed by a repeattest.

14. Biliary impairment sufficient to affect participant safety, or total bilirubinlevels > 1.5 × ULN at screening or Baseline visit and confirmed by a repeat test. Incases of Gilbert's Syndrome, resulting in stable levels of total bilirubin greaterthan ULN, the medical monitor can determine if a protocol exception can be made

15. Renal impairment sufficient to affect participant safety, or estimated glomerularfiltration rate (eGFR) < 30 milliliter per minute (mL/min) (calculated using theCockcroft-Gault formula or Pediatric GFR calculator or Bedside Schwartz), will beexcluded from study entry or will be discontinued if the criterion is met postBaseline. Cases of temporary renal insufficiency should be discussed with themedical monitor to determine the participant's study continuation.

16. Exposed to any other investigational drug or investigational device within 30 daysor fewer than 5 half-lives prior to the screening visit. For therapies in whichhalf-life cannot be readily established, the Sponsor's Medical Monitor should beconsulted.

17. Unwillingness to avoid excessive alcohol use throughout the study.

18. Have active suicidal plan/intent, active suicidal thoughts or a suicide attempt inthe past 6 months.

19. Known sensitivity or allergy to any component in the IP(s), progesterone, or otherrelated steroid compounds.

20. Participants deprived of their liberty by a judicial or administrative decision, orfor psychiatric treatment, or participants admitted to a health or social servicesfacility for purposes other than research.

21. Participants receiving traditional Chinese medicine therapies within the prior 28days of the screening.