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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04737174


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04737174
Ethics application status
Date submitted
26/01/2021
Date registered
3/02/2021
Date last updated
6/04/2022

Titles & IDs
Public title
ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors
Scientific 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
Secondary ID [1] 0 0
EST-481 2020-Onco-101-HGG
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy; Seizure 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ES-481

Experimental: ES-481 - Administered as 25 mg oral gelatin capsules


Treatment: Drugs: ES-481
28-day screening period followed by 4-week dose escalation period followed by 16-week treatment period followed by 4-week dose washout period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Electroencephalogram Monitoring of epileptiform interictal and seizure discharge
Timepoint [1] 0 0
Continual 24 hours
Primary outcome [2] 0 0
Subject Captured Seizure Activity
Timepoint [2] 0 0
Continual 24 hour

Eligibility
Key inclusion criteria
1. Subjects greater than 18 years of age

2. Subjects with brain tumour-related epilepsy

3. Subjects with a history of uncontrolled seizures (at least three focal-onset seizure
per month over the last 28 days)

4. Subjects currently being treated with at least one appropriate AED

5. Subjects who have had a brain MRI performed in the last three months preceding the
signing of informed consent

6. Subjects with primary brain tumour with an IDH1 mutation (to be determined during the
screening period)

7. Subjects with satisfactory hematologic, renal and liver function, as assessed by the
Principal Investigator

8. Subject with a Karnofsky performance scale index (KPD) of > 70%

9. An expected survival time > 6 months

10. 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:

1. 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)

2. 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

11. 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

12. Willing to participate in the study and willing to provide written signed informed
consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Urgent need for surgical intervention

2. Alanine aminotransferase or aspartate aminotransferase > 10 times the upper reference
limit at the screening visit

3. Estimated glomerular filtration rate < 60 mL/min (calculated using the using the
Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation) at the
screening visit

4. 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

5. Factors that significantly affect oral drug absorption, such as inability to swallow,
chronic diarrhoea, short bowel syndrome, and/or intestinal obstruction

6. Hypertension that cannot be reduced to normal range with antihypertensive medication
(systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)

7. Concurrent active cancer that requires non-surgical treatment (e.g., chemotherapy,
radiotherapy, adjuvant therapy)

8. 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

9. 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

10. 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%.

11. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
25/03/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2022
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ES Therapeutics Australia Pty Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 potential anti-tumorigenic effects.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04737174
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Terence O'Brien, MD
Address 0 0
The Alfred Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04737174

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Funding & Sponsors
Primary sponsor
Commercial sector/Industry
Primary sponsor name
ES Therapeutics Australia Ltd Pty
Primary sponsor address
C/O Prime Accounting and Business Advisory Services
Level 17, 40 City Road
Southbank, VIC 3006
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
Ethics committee name [1] 23
Alfred HREC
Address [1] 23
55 Commercial Road Melbourne VIC 3004
Country [1] 23
Australia
Date submitted for ethics approval [1] 23
18/01/2021
Approval date [1] 23
25/03/2021
Ethics approval number [1] 23
HREC72849/Alfred-2021
 
Public notes

Contacts
Principal investigator
Title 221 0
Dr
Name 221 0
Sanjeev Gill
Address 221 0
Alfred Hospital 55 Commercial Road Melbourne VIC 3004
Country 221 0
Australia
Phone 221 0
Fax 221 0
Email 221 0
Contact person for public queries
Title 222 0
Dr
Name 222 0
Robert Niecestro
Address 222 0
ES Therapeutics, Inc. 129 Conifer Lane # 604 Pocono Pines, PA 18350
Country 222 0
United States of America
Phone 222 0
+61 3 9013 4220
Fax 222 0
Email 222 0
Contact person for scientific queries
Title 223 0
Dr
Name 223 0
Robert Niecestro
Address 223 0
ES Therapeutics, Inc. 129 Conifer Lane # 604 Pocono Pines, PA 18350
Country 223 0
United States of America
Phone 223 0
+61 3 9013 4220
Fax 223 0
Email 223 0