ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)
Condition: Epilepsy Intractable
MeSH terms: Epilepsy; Drug Resistant Epilepsy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a prospective, single-center, phase 1 safety study to investigate the safety,
      tolerability, seizure control, and quality of life in participants with medically-refractory
      epilepsy who failed epilepsy surgery. These participants will have continued seizures despite
      being at least 3 months post-epilepsy surgery (resective surgery with an intent to cure).
    

Detailed description: 
      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.
    

Intervention name(s): ABI-009
Intervention type(s): Drug
Intervention description(s): For dose finding, ABI-009 will start at 5 mg/m2/dose IV, once a week for three weeks, in cohorts of 3 participants each using the standard 3+3 dose-finding design
Intervention model: Single Group Assignment
Intervention model description: Participation includes a 4-week baseline period, a 3-week dosing period and a 12-week follow-up period. After baseline participants will receive ABI-009 given weekly IV for 3 weeks. ABI-009 will be tested in cohorts of 3 participants using the standard 3+3 dose-finding design.
Escalation to the next dose level with a new cohort of 3 participants will occur after no DLT was observed. There will be no intra-participant dose escalation allowed. If DLT occurs in a cohort, an additional 3 participants will be recruited to the cohort. If no further DLTs occur, a new cohort of 3 participants at the next higher dose level can be enrolled. If 2/6 participants at dose level 1 experience a DLT, then that cohort will be closed to further enrollment and 3 participants will be enrolled at the next lower dose level, and so on. The MTD is the highest dose level in which ≤1 participant has a DLT.
Once MTD has been determined, MTD cohort will be opened for up to 6 additional participants.
Masking: None (Open Label)
Primary purpose: Treatment