Epilepsy IntractablePhase 1NCT03646240
ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)
A Phase 1 study testing ABI-009 in people with Epilepsy Intractable, run by Seattle Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 26 years
- Conditions the study is for
- Epilepsy Intractable
- What is being tested?
- ABI-009
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2018to 31 Dec 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 26 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Written informed consent (and assent when applicable) obtained from participant or participant's legal representative
- Be willing and able to adhere to the study visit schedule and other protocol requirements
- 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.
- 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)
- Documentation of resective epilepsy surgery following appropriate pre-surgical evaluation
- 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.
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- Documentation that the participant is not a candidate for OR refuses any additional resective epilepsy surgery
- 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.
- Participants must have adequate liver function (SGPT/ALT ≤5 times ULN and bilirubin ≤5 times ULN) before starting study drug.
- 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:
- 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.
- Participants must have normal oxygen saturation.
- 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.
- Participants of child bearing potential must not be breastfeeding or pregnant as evidenced by a negative pregnancy test.
Who cannot join
- For females of child bearing potential:
- Positive pregnancy test at Visit 1, or
- Lactating, or
- 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.
- 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.
- 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.
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- 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.
- 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.
- 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.
- Patients who have been previously treated with a systemic mTOR inhibitor for epilepsy. Skin cream use with rapamycin or everolimus, however, is permitted.
- Patients with a known hypersensitivity to human albumin, ABI-009 or other rapamycins (e.g. sirolimus, everolimus, temsirolimus).
- 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.
- Patients with any clinically significant unrelated systemic illness that would compromise a participant's ability to tolerate protocol procedures.
- Patients with inability to return for dosing and follow-up visits to assess toxicity to the study drug.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Seattle Children's Hospital
Seattle, Washington, 98105
About this study
Official title: Phase 1 Study of ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)
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).
Read the 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.
- Conditions
- Epilepsy Intractable
- Being tested
- ABI-009
- Medical subject headings
- Drug Resistant Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABI-009Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Dosing arm | Experimental | Not described Receives: Drug: ABI-009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose
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.
Measured: 3 weeks
Secondary outcomes (1)
Percentage reduction in seizure rate
Frequency measured using median percentage reduction
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start31 Jul 2018
- Primary completion22 Aug 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy IntractableStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Aadi Bioscience, Inc.
- Responsible party
- Principal investigator, Jason Hauptman, Seattle Children's Hospital
- Investigators
- Jason Hauptman, MD, PhD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646240
- Sponsor's protocol ID
- RaSuRE
- Status last verified
- May 2023
- First submitted
- 19 Jul 2018
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of ABI-009 (Nab-rapamycin) for Surgically-Refractory Epilepsy (RaSuRE)
- ClinicalTrials.gov ID
- NCT03646240
- Acronym / sponsor ID
- RaSuRE
- Conditions
- Epilepsy Intractable
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Collaborators
- Aadi Bioscience, Inc.
- Study start
- 31 Jul 2018 (actual)
- Primary completion
- 22 Aug 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dosing arm | Experimental | Drug: ABI-009 |
Who may qualify
- Ages
- 3 to 26 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Written informed consent (and assent when applicable) obtained from participant or participant's legal representative
- Be willing and able to adhere to the study visit schedule and other protocol requirements
- 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.
- 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)
- Documentation of resective epilepsy surgery following appropriate pre-surgical evaluation
Key exclusion criteria (15 listed)
- For females of child bearing potential:
- 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.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ABI-009For 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 | Drug | Dosing arm |
Primary outcome
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.
1 secondary outcome
Percentage reduction in seizure rate
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Hauptman, MD, PhD principal investigator
Seattle Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ABI-009 in people with Epilepsy Intractable, run by Seattle Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.