ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)

Seizures that are refractory to both medical and surgical therapy increase the risk of
morbidity and mortality in children with epilepsy. At this point in time, options for these
children are sparse and suboptimal. This hypothesis-driven phase 1 study aims to evaluate the
use of a mammalian target of rapamycin [mTOR] inhibitor, ABI-009, in this subset of
challenging participants. The underlying hypotheses being tested in trial are: (1) ABI-009 is
a safe and well-tolerated medication in children who have medically-refractory epilepsy and
have failed epilepsy surgery, and (2) The addition of ABI-009 therapy to the current clinical
standard of continued antiepileptic medications results in improved epilepsy control. This is
unique among trials of anti-epileptic medications in that it also studies mTOR inhibition in
a non-Tuberous Sclerosis Complex (TSC) specific population for whom few additional effective
therapies exist.

Upon enrollment, participants will be continued and observed on their pre-existing,
clinically prescribed antiepileptic drug (AED) regimen for 1 month. At the 1-month mark,
participants will receive weekly ABI-009 intravenously at different dose levels in cohorts of
3 participants each using the standard 3+3 dose-finding design. ABI-009 will be continued for
a total of 3 weeks. ABI-009 will then be discontinued and the participants will be observed
for an additional 3 months. The investigators intend an expansion of the maximum tolerated
dose (MTD) cohort to an estimated additional 6 participants for a maximum possible enrollment
of 18 participants.

Inclusion Criteria:

1. Written informed consent (and assent when applicable) obtained from participant or
participant's legal representative

2. Be willing and able to adhere to the study visit schedule and other protocol
requirements

3. Male or female ≥3 and ≤26 years of age at Visit 1 b. Because no dosing or adverse
event data are currently available on the use of ABI-009 or other mTOR inhibitors in
participants <3 years of age, these young children are excluded from this study.

4. Documentation of a diagnosis of medically intractable epilepsy as defined by the
failure of at least 2 appropriately dosed and tolerated AEDs to eliminate all clinical
seizures over a 6-month period (prior to epilepsy surgery)

5. Documentation of resective epilepsy surgery following appropriate pre-surgical
evaluation

6. Documentation of continued clinical seizures that persist at least 3 months following
resective epilepsy surgery. In order to proceed with drug administration, participants
will have to have had >8 seizures in the last 30 days without 2 weeks of seizure
freedom, as noted by a daily seizure diary.

7. Documentation that the participant is not a candidate for OR refuses any additional
resective epilepsy surgery

8. Participants must have adequate bone marrow function (ANC ≥1,000/mm3, platelet count
of ≥100,000/mm3, and hemoglobin ≥9 gm/dL) before starting study drug.

9. Participants must have adequate liver function (SGPT/ALT ≤5 times ULN and bilirubin ≤5
times ULN) before starting study drug.

10. Participants must have adequate renal function, defined as: Creatinine clearance or
radioisotope GFR >/= 70mL/min/1.73 m2 or a serum creatinine based on age/gender as
follows:

11. Participants must have a fasting cholesterol level <350 mg/dL and triglycerides <400
mg/dL before starting study drug. In case one or both of these are exceeded, the
participant can only be included after initiation of appropriate lipid lowering
medication and documentation of cholesterol <350mg/dL and triglycerides <400mg/dl
before start of study drug.

12. Participants must have normal oxygen saturation.

13. The effects of ABI-009 on the developing human fetus at the recommended therapeutic
dose are unknown. For this reason and because rapamycin is known to be teratogenic,
female participants of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation. Should a female participant become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately.

1. Participants of child bearing potential must not be breastfeeding or pregnant as
evidenced by a negative pregnancy test.

Exclusion Criteria:

1. For females of child bearing potential:

1. Positive pregnancy test at Visit 1, or

2. Lactating, or

3. Unwilling to practice a medically acceptable form of contraception (acceptable
forms of contraception: abstinence, hormonal birth control, intrauterine device,
or barrier method plus a spermicidal agent), unless surgically sterilized or
postmenopausal during the study.

2. Has any other condition that, in the opinion of the Site Investigator/designee, would
preclude informed consent or assent, make study participation unsafe, complicate
interpretation of study outcome data, or otherwise interfere with achieving the study
objectives.

3. Participants should not receive immunization with attenuated live vaccines within one
week of study entry or during study period. Close contact with those who have received
attenuated live vaccines should be avoided during the ABI-009 dosing period. Examples
of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio,
BCG, yellow fever, varicella and TY21a typhoid vaccines.

4. HBsAg and HCVAb blood test must be done at screening (HBsAg only needs to be screened
in patients who have not received the full complement of Hepatitis B immunizations).
Patients who test positive for Hepatitis C antibodies or the Hepatitis B antigen are
ineligible. Alternatively, if the patient has received the complement of Hepatitis B
immunizations, this would suffice.

5. A known history of HIV seropositivity. HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with ABI-009. In addition, these patients are at increased risk of lethal
infections when treated with marrow-suppressive therapy.

6. Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Note: Patients that are currently using inhaled, intranasal,
ocular, topical or other non-oral or non-IV steroids are not necessarily excluded from
the study but need to be discussed with the study chair.

7. Patients who have been previously treated with a systemic mTOR inhibitor for epilepsy.
Skin cream use with rapamycin or everolimus, however, is permitted.

8. Patients with a known hypersensitivity to human albumin, ABI-009 or other rapamycins
(e.g. sirolimus, everolimus, temsirolimus).

9. Patients receiving any other concurrent anticancer or investigational therapy.
Participants will be permitted to enroll in the study after a 30-day washout of
previously used investigational drugs.

10. Patients with any clinically significant unrelated systemic illness that would
compromise a participant's ability to tolerate protocol procedures.

11. Patients with inability to return for dosing and follow-up visits to assess toxicity
to the study drug.

12. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, active lung disease, or psychiatric illness/social situations that would
limit compliance with study requirements. Study Specific Tolerance for
Inclusion/Exclusion Criteria Patients who fail to meet one or more of the inclusion
criteria or who meet any of the exclusion criteria will not be enrolled in this study.
Waivers of any of the above study entry criteria will not be granted.