Adjunctive Everolimus (RAD 001) Therapy for Epilepsy in Children With Sturge-Weber Syndrome (SWS)
Adjunctive Everolimus (RAD 001) Therapy for Epilepsy in Children With Sturge-Weber Syndrome (SWS)
Sturge Weber Syndrome (SWS) is a rare disease that affects the patient's brain and causes
 benign (non-cancerous) tumors to grow in the brain. One of the symptoms of SWS is epilepsy.
 People with epilepsy have seizures. Some patients may also have eye problems and a red mark
 on their facial skin.

 This study is being done to find out if the study drug, everolimus, is safe and has helpful
 effects in patients with SWS who have seizures and are not responding to their current
 anti-epileptic medication.

 The study drug, everolimus (Afinitor®), is supplied by Novartis Pharmaceuticals Corporation.
The main study part has 3 phases. The first phase is called the baseline phase and consists
 of 1-2 study site visit(s). During this phase, the investigators will gather information
 about the subject, his/her medical history, and current health.

 During the second phase of the study, the subject will start taking the study drug. It will
 take approximately 4 weeks to find out the right amount of study drug the subject should be
 taking. This process is called the titration phase. There will be 2 visits during the
 titration phase.

 Once the subject are on the right amount of study drug, he/she will take that dose for about
 12 weeks. This phase is called the maintenance phase and consists of 3 study site visits.

 At the end of the maintenance phase, if the study doctor determines that taking everolimus
 has helped to reduce the number of seizures the subject has, he/she will have the choice to
 continue taking the study drug for an extended time. There will be 4 total study site visits
 during the extension phase.

 Study assessments:

 1. Medical History: A detailed medical history will be given and the subject's medical
 record will be reviewed by the study team to verify inclusion and exclusion criteria.

 2. Vital Signs: Weight, height, blood pressure, pulse rate, and body temperature, will be
 recorded.

 3. Physical Exam: A standard physical examination will be performed at baseline, week 4,
 16, and month 6 and 12 of extension visits.

 4. Neurological Exam: A standard neurological examination will be performed at baseline,
 week 4, 16, and month 6 and 12 of extension visits.

 5. Dermatological Exam: A skin examination will be performed to assess the presence and
 characteristics of Port-wine stain birthmarks.

 6. Ophthalmologic Exam: An eye examination will be performed to evaluate for the presence
 of glaucoma. Visual acuity, tonometry, and visual fields will be assessed.

 7. Safety Laboratory Assessments: Safety laboratory assessments will be performed at
 baseline, week 4, week 8, week 16, and every 3 months thereafter in the extension phase
 of the study.

 8. Pregnancy testing: For females of child-bearing potential, serum pregnancy will be
 performed at screening and at every visit where safety laboratory assessments are being
 done.

 9. Antiepileptic Drug (AED) Concentrations: AED levels specific to each subject will be
 performed at baseline, week 2, week 4, week 8, week 16, and every 3 months thereafter in
 the extension phase of the study. This test is done to determine the blood level of
 other anti-epileptic drugs the participant may be taking.

 10. Everolimus Concentrations: Everolimus levels will be performed after the start of study
 medication at week 2, week 4, week 8, week 16, and every 3 months thereafter in the
 extension phase of the study. This test is done to determine the dose level of the study
 drug that will be given at each visit.
Inclusion Criteria:

 -  2-18 years of age, male and female.

 -  Subject weights greater than or equal to 6 kg at study entry.

 -  Subjects clinically diagnosed with SWS, inclusive of cerebral and dermatologic
 involvement. Ophthalmic involvement will be monitored if present, but is not necessary
 for enrollment.

 -  History of epilepsy with a history of at least 4 seizures in the month prior to
 screening.

 -  Medically refractory epilepsy defined as failure of two or more approved antiepileptic
 therapies.

 -  Females of child-bearing potential must use highly effective contraception during the
 study and for 8 weeks after stopping treatment.

 -  Sexually active males must use a condom during intercourse while taking study drug,
 and for 8 weeks after stopping study treatment.

 -  Adequate bone marrow function.

 -  Adequate liver function.

 -  Adequate renal function.

 -  Acceptable fasting serum cholesterol and fasting triglycerides levels.

 Exclusion Criteria:

 -  Patients currently receiving anticancer therapies or who have received anticancer
 therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation
 therapy, antibody based therapy, etc.).

 -  Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs.

 -  Known impairment of gastrointestinal (GI) function or GI disease that may
 significantly alter the absorption of oral Everolimus.

 -  Uncontrolled diabetes mellitus despite adequate therapy.

 -  Patients who have any severe and/or uncontrolled medical conditions.

 -  Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
 inhaled corticosteroids are allowed.

 -  Known history of HIV seropositivity.

 -  Patients who have received live attenuated vaccines within 1 week of start of
 Everolimus and during the study.

 -  Patients who have a history of another primary malignancy, with the exceptions of:
 non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from
 which the patient has been disease free for ≥3 years.

 -  Patients with a history of non-compliance to medical regimens or who are considered
 potentially unreliable or will not be able to complete the entire study.

 -  Patients who are currently part of or have participated in any clinical investigation
 with an investigational drug within 1 month prior to dosing.

 -  Pregnant or nursing (lactating) women.