ES-481 for Uncontrolled Glioma-Associated Epilepsy and Assessment for Potential Anti-Tumorigenic Effect in Patients With Isocitrate Dehydrogenase 1 (IDH1) Mutant Tumors

NCT04737174 | Withdrawn Phase 2

• 1 other identifier: EST-481 2020-Onco-101-HGG
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Epilepsy; Seizure

Outcome Measures

Primary Outcomes (2)

• Electroencephalogram Monitoring of epileptiform interictal and seizure discharge

  Continual 24 hours

• Subject Captured Seizure Activity

  Subjects will keep daily diary of seizure activity

  Continual 24 hour

Study Arms (1)

ES-481

EXPERIMENTAL

Administered as 25 mg oral gelatin capsules

Drug: ES-481

Interventions

ES-481 DRUG

28-day screening period followed by 4-week dose escalation period followed by 16-week treatment period followed by 4-week dose washout period

ES-481

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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)
• 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
• 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%.

Sponsors & Collaborators

• ES Therapeutics Australia Pty Ltd: lead

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Terence O'Brien, MD

  The Alfred Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 3, 2021
• Study Start: March 25, 2021
• Primary Completion: October 1, 2021
• Study Completion: April 1, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-03