A Phase 2 Study of CX-8998 in Adolescents and Young Adults With Generalized Epileptic Syndromes With Absence Seizures
This is a Phase 2a, multicenter, double-blind, placebo-controlled, parallel-group study consisting of a screening period of up to 4 weeks, a 4 week randomized double-blind, dose-titration treatment period, followed by a 1 week safety follow-up period after the last dose of study medication.
Study Start Date
January, 31 2018
Estimated Completion Date
- Drug: CX-8998
- Drug: Placebo Comparator
Cavion LLC -- CX-8998-CLN2-002
1. Signed informed consent form (ICF) indicating that the subject has been informed of
the procedures to be followed, the experimental nature of the therapy, alternatives,
potential benefits, side effects, risks, and discomforts.
2. Men or non-pregnant, non-breastfeeding women 16 to 45 years-of-age who are able to
read and understand written and spoken local language.
3. Diagnosis: Clinical diagnosis of an epileptic syndrome (including, but not limited to,
childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, or
Jeavons syndrome) with absence seizures consistent with the International League
against Epilepsy Revised Classification of Seizures (2017).
4. Absence seizures persisting despite documented trials with at least two standard
5. Observation of at least 3 instances of bilateral synchronous symmetrical spike waves
of approximately 2.5
- 4 Hz lasting >3 seconds via 24-hr ambulatory EEG (centrally reviewed). 6. On no therapy or taking stable doses of one or more anti-epileptic medication(s) for at least 30 days. If a subject is not on medication, adequate documentation justifying lack of therapy is acceptable. Ketogenic, modified Atkins (MAD), or low glycemic diet with stable carbohydrate ratio for at least 30 days is an acceptable antiepileptic therapy. Vagal nerve stimulation at stable settings, without use of the magnet, is also acceptable. 7. Body weight ? 45 kg at screening. 8. Subjects with reproductive capability including all males and women of child-bearing potential (WOCBP) must agree to practice continuous abstinence or adequate contraception methods (appropriate double barrier method or oral, patch, implant, or injectable contraception) from as soon as feasible during screening period until at least 30 days after the last dose (i.e., intermittent abstinence based on "rhythm", temperature monitoring, or other means of timing is not acceptable). WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy) or is not post-menopausal. Post-menopausal is defined as amenorrhea ? 12 consecutive months without another cause, and a documented serum follicle stimulating hormone (FSH) level ? 35 mIU/mL. 9. Male subjects with a partner of child-bearing potential must be surgically sterilized or be willing to use condoms with spermicide from as soon as feasible during screening period until at least 30 days after the last dose. 10. Able and willing to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. 11. Approval by the sponsor medical personnel or delegate as to final eligibility for the study.
1. History of focal epilepsy or epileptiform patterns consistent with focal epilepsy
during screening measured by 24-hr ambulatory EEG.
2. History of surgical intervention for treatment of epilepsy.
3. Inadequately treated psychotic or mood disorder (e.g., schizophrenia, major
depression, bipolar disorder).
4. Presence of severe intellectual disability, severe autism spectrum disorder or severe
5. Presence of positive urine drug screen for drugs of abuse, except if this is explained
by use of an allowed prescription medicine.
6. Regular use of more than one standard drink of alcohol per day (14 grams of pure
7. Hypersensitivity/allergic reaction to other T-type calcium agents, such as (but not
limited to) ethosuximide and zonisamide.
8. Use of strong CYP3A4 inhibitors, including prescription or non-prescription drugs or
other products (i.e. grapefruit juice), which cannot be discontinued at least 2 weeks
prior to Day 1 of dosing and throughout the study (Appendix C).
9. Concurrent illnesses that would be a contraindication to trial participation,
including, but not limited to:
1. Severe arterial thromboembolic events (myocardial infarction, unstable angina
pectoris, stroke) less than 6 months before screening
2. NYHA Class III or IV congestive heart failure, ventricular arrhythmias or
3. Clinically significant ECG abnormality per the Investigator assessment or any of
the following: i) QTcF ?450 msec (males) or ?470 msec (females) ii) PR interval
?250 msec iii) Atrioventricular block of second degree or higher, including
Mobitz I iv) Persistent sinus bradycardia ? 50 beats per minute persistent means
the bradycardia is present on the first ECG and on one repeat ECG performed on
another day v) For other ECG findings (e.g., including, but not necessarily
limited to, tachycardia, bundle branch block, frequent ectopic beats, etc.) the
Investigator should send a scanned, identity-blinded copy of the ECG tracing to
the Study Safety Representative for review.
10. Positive result for HIV, Hepatitis B [indicating ongoing infection], or Hepatitis C at
screening or otherwise known ongoing infection with HIV, hepatitis B, or hepatitis C,
unless curative therapy completed for hepatitis C curative therapy is defined as
negative PCR for HCV RNA.
11. Significant hepatic (AST/ALT or bilirubin ? 2X upper limit of normal) or renal disease
(creatinine clearance ?39 mL/min) at screening.
12. History of alcohol or substance abuse within the last year.
13. A current C-SSRS score of 4 or 5 at screening or history of suicide attempt at any
time during the past year.
14. Psychological, social, familial, or geographical reasons that would hinder or prevent
compliance with the requirements of the protocol or compromise the informed consent
15. Any other condition and/or situation that causes the Investigator or Study Safety
Representative to deem a subject unsuitable for the study (e.g., due to expected study
medication non-compliance, inability to medically tolerate the study procedures, or a
subject's unwillingness to comply with study-related procedures).
16. Treatment with an investigational agent within 30 days prior to the first dose of
CX-8998 or planning to receive an investigational agent during the study.
16 Years to 45 Years
Accepts Healthy Volunteers
Study Locations and Contact Information (7)
|NYU Comprehensive Epilepsy Center - New York, New York||186.5 miles||Stephanie Tenzigolskifirstname.lastname@example.org|
|Thomas Jefferson University - Philadelphia, Pennsylvania||269.5 miles||Jessica Rinaldiemail@example.com|
|MidAtlantic Epilepsy and Sleep Center - Bethesda, Maryland||394.0 miles||Arkady Barberfirstname.lastname@example.org|
|Cincinnati Childrens Hospital - Cincinnati, Ohio||735.6 miles||Peggy Clark||None||Peggy.Clark@cchmc.org|
|Bluegrass Epilepsy Research LLC - Lexington, Kentucky||770.3 miles||Amber Clark||859-313-4210||AmberClark@sjhlex.org|
|Center for Rare Neurological Diseases - Norcross, Georgia||920.7 miles||None||None||None|
|Medsol Clinial Research Center Inc - Port Charlotte, Florida||1,249.0 miles||Maria Vasconcelosemail@example.com|