ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)
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|ClinicalTrials.gov Identifier: NCT03646240|
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : October 22, 2020
|Condition or disease||Intervention/treatment||Phase|
|Epilepsy Intractable||Drug: ABI-009||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|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)|
|Official Title:||Phase 1 Study of ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)|
|Actual Study Start Date :||July 31, 2018|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
|Experimental: Dosing arm||
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
- Maximum tolerated dose [ Time Frame: 3 weeks ]Incidence of AEs in each treatment arm will be tabulated by seriousness, severity, and relationship to study drug from baseline will be summarized by treatment group.
- Percentage reduction in seizure rate [ Time Frame: 4 months ]Frequency measured using median percentage reduction
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646240
|Contact: Jani Kleinemail@example.com|
|Contact: Jason Hauptman, MD, PhDfirstname.lastname@example.org|
|Principal Investigator:||Jason Hauptman, MD, PhD||Seattle Children's Hospital|