Epilepsy; SeizurePhase 2NCT04737174
ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors
A Phase 2 study testing ES-481 in people with Epilepsy; Seizure, run by ES Therapeutics Australia Pty Ltd.
Trial summary
Phase 2A single-arm exploratory clinical study in up to 12 adult subjects aged 18 and older with primary glioma, IDH1 mutation, and uncontrolled focal-onset seizure activity to determine the potential efficacy, safety and pharmacokinetics of ES-481 as adjunctive therapy in glioma-associated epilepsy and to assess for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy; Seizure
- What is being tested?
- ES-481
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 25 Mar 2021to Apr 2022
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects greater than 18 years of age
- Subjects with brain tumour-related epilepsy
- Subjects with a history of uncontrolled seizures (at least three focal-onset seizure per month over the last 28 days)
- Subjects currently being treated with at least one appropriate AED
- Subjects who have had a brain MRI performed in the last three months preceding the signing of informed consent
- Subjects with primary brain tumour with an IDH1 mutation (to be determined during the screening period)
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- Subjects with satisfactory hematologic, renal and liver function, as assessed by the Principal Investigator
- Subject with a Karnofsky performance scale index (KPD) of > 70%
- An expected survival time > 6 months
- A female subject is eligible to participate if she is not pregnant by serum pregnancy test, not breastfeeding, and at least 1 of the following conditions applies:
- Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient)
- Of childbearing potential and agrees to use a highly effective method of contraception consistently during the 4-week dose escalation, 16-week treatment, and 4-week washout periods; and for at least 30 days after the last dose of study treatment
- A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during 4-week dose escalation, 16-week treatment, and 4-week washout periods; and for at least 30 days after the last dose of study treatment and refrains from donating sperm during this period
- Willing to participate in the study and willing to provide written signed informed consent.
Who cannot join
- Urgent need for surgical intervention
- Alanine aminotransferase or aspartate aminotransferase > 10 times the upper reference limit at the screening visit
- Estimated glomerular filtration rate < 60 mL/min (calculated using the using the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) at the screening visit
- Any haematological National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Grade ≥ 3 (with the exception of alopecia) at the screening visit
- Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhoea, short bowel syndrome, and/or intestinal obstruction
- Hypertension that cannot be reduced to normal range with antihypertensive medication (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)
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- Concurrent active cancer that requires non-surgical treatment (e.g., chemotherapy, radiotherapy, adjuvant therapy)
- History of severe cardiovascular disease: myocardial ischemia or myocardial infarction of Grade 2 or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men, ≥470 ms for women); according to New York Heart Association standards, Grade 3 or 4 cardiac insufficiency, or colour doppler ultrasound examination of the left ventricular ejection fraction < 50% as assessed at the screening visit
- In the Investigators opinion, the subject's involvement may affect the progress of the clinical study and/or the determination of the research results, and/or considers them unsuitable for inclusion
- Previously suffered severe cardiovascular disease: myocardial ischemia or myocardial infarction of Grade 2 or above, poorly controlled arrhythmia (including QTc interval ≥450 ms for men, ≥470 ms for women); according to New York Heart Association standards, Grade 3 or 4 cardiac insufficiency, or color doppler ultrasound examination of the left ventricular ejection fraction < 50%.
- Investigator judges that may affect the progress of the clinical study and/or the determination of the research results, and/or considers them unsuitable for inclusion.
About this study
Official title: Adjunctive ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors
Phase 2A single-arm exploratory clinical study in up to 12 adult subjects aged 18 and older with primary glioma, IDH1 mutation, and uncontrolled focal-onset seizure activity to determine the potential efficacy, safety and pharmacokinetics of ES-481 as adjunctive therapy in glioma-associated epilepsy and to assess for potential anti-tumorigenic effects.
- Conditions
- Epilepsy; Seizure
- Being tested
- ES-481
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ES-481Drug
28-day screening period followed by 4-week dose escalation period followed by 16-week treatment period followed by 4-week dose washout period
| Study group | Role | What they receive |
|---|---|---|
| ES-481 | Experimental | Administered as 25 mg oral gelatin capsules Receives: Drug: ES-481 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electroencephalogram Monitoring of epileptiform interictal and seizure discharge
Measured: Continual 24 hours
Subject Captured Seizure Activity
Subjects will keep daily diary of seizure activity
Measured: Continual 24 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start25 Mar 2021 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionApr 2022 (estimated)
Why it stopped: Lack of identifiable patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsy; SeizureStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- ES Therapeutics Australia Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Terence O'Brien, MD, Principal investigator, The Alfred Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04737174
- Sponsor's protocol ID
- EST-481 2020-Onco-101-HGG
- Status last verified
- Mar 2022
- First submitted
- 26 Jan 2021
- Last updated
- 6 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors
- ClinicalTrials.gov ID
- NCT04737174
- Acronym / sponsor ID
- EST-481 2020-Onco-101-HGG
- Conditions
- Epilepsy; Seizure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of identifiable patients
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ES Therapeutics Australia Pty LtdIndustry (pharma, biotech, devices)
- Study start
- 25 Mar 2021 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 3 Feb 2021 (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.
Phase 2A single-arm exploratory clinical study in up to 12 adult subjects aged 18 and older with primary glioma, IDH1 mutation, and uncontrolled focal-onset seizure activity to determine the potential efficacy, safety and pharmacokinetics of ES-481 as adjunctive therapy in glioma-associated epilepsy and to assess for potential anti-tumorigenic effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ES-481 | Experimental | Drug: ES-481Administered as 25 mg oral gelatin capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subjects greater than 18 years of age
- Subjects with brain tumour-related epilepsy
- Subjects with a history of uncontrolled seizures (at least three focal-onset seizure per month over the last 28 days)
- Subjects currently being treated with at least one appropriate AED
- Subjects who have had a brain MRI performed in the last three months preceding the signing of informed consent
Key exclusion criteria (11 listed)
- Urgent need for surgical intervention
- Alanine aminotransferase or aspartate aminotransferase > 10 times the upper reference limit at the screening visit
- Estimated glomerular filtration rate < 60 mL/min (calculated using the using the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) at the screening visit
- Any haematological National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Grade ≥ 3 (with the exception of alopecia) at the screening visit
- Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhoea, short bowel syndrome, and/or intestinal obstruction
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 |
|---|---|---|
| ES-48128-day screening period followed by 4-week dose escalation period followed by 16-week treatment period followed by 4-week dose washout period | Drug | ES-481 |
Primary outcome
Electroencephalogram Monitoring of epileptiform interictal and seizure discharge
Time frame: Continual 24 hours
Subject Captured Seizure Activity
Time frame: Continual 24 hour
Subjects will keep daily diary of seizure activity
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2022.
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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.
Terence O'Brien, MD principal investigator
The Alfred Centre
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ES-481 in people with Epilepsy; Seizure, run by ES Therapeutics Australia Pty Ltd.
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 11 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: withdrawn, as of the sponsor's last update on 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Electroencephalogram Monitoring of epileptiform interictal and seizure discharge (time frame: Continual 24 hours). The study lists 2 primary outcomes in all. 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 Apr 2022.