| CTRI Number |
CTRI/2023/04/051812 [Registered on: 20/04/2023] Trial Registered Prospectively |
| Last Modified On: |
27/06/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A study to compare efficacy of EPX-100 in the treatment of Dravet Syndrome. |
|
Scientific Title of Study
|
A 20-Week Multicenter, Randomized, Double-Blind, Placebo Controlled Trial of EPX-100 (Clemizole Hydrochloride) as
Adjunctive Therapy in Children and Adult Participants with
Dravet Syndrome (ARGUS Trial) |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| Protocol No EPX-100-001 Version 8.0 dated February 28, 2023 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Umakanta Sahoo |
| Designation |
Managing Director |
| Affiliation |
GCT Pharma Research (India) Pvt Ltd |
| Address |
7th Floor, Wing-B,
Vatika Business Centre, Hiranandani Gardens, Powai,
Mumbai
Mumbai
MAHARASHTRA
400076
India |
| Phone |
912242369729 |
| Fax |
|
| Email |
U.Sahoo@gctrials.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Umakanta Sahoo |
| Designation |
Managing Director |
| Affiliation |
GCT Pharma Research (India) Pvt Ltd |
| Address |
7th Floor, Wing-B,
Vatika Business Centre, Hiranandani Gardens, Powai,
Mumbai,
Mumbai
MAHARASHTRA
400076
India |
| Phone |
912242369729 |
| Fax |
|
| Email |
U.Sahoo@gctrials.com |
|
Details of Contact Person
Public Query
|
| Name |
Umakanta Sahoo |
| Designation |
Managing Director |
| Affiliation |
GCT Pharma Research (India) Pvt Ltd |
| Address |
7th Floor, Wing-B,
Vatika Business Centre, Hiranandani Gardens, Powai,
Mumbai,
Mumbai
MAHARASHTRA
400076
India |
| Phone |
912242369729 |
| Fax |
|
| Email |
U.Sahoo@gctrials.com |
|
|
Source of Monetary or Material Support
|
| M/s GCT Pharma Research (India) Pvt Ltd,
7th Floor, Wing-B, Vatika Business Centre, Hiranandani Gardens, Powai,
Mumbai , Maharashtra (India) - 400076
Telephone No.: 912242369729 |
|
|
Primary Sponsor
|
| Name |
Epygenix Therapeutics, Inc |
| Address |
140 E. Ridgewood Avenue
Suite 415, South Tower
Paramus, NJ 07652 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Epygenix Therapeutics Inc |
140 E. Ridgewood Avenue
Suite 415, South Tower
Paramus, NJ 07652 |
|
|
Countries of Recruitment
|
Bulgaria
Canada
Georgia
Hungary
Poland
Romania
Spain
United Kingdom
United States of America
India |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Atul Jindal |
AIIMS |
Department of neurology, G. E. Road, Tatibandh, Raipur,
Chhattisgarh -492099
Raipur
CHHATTISGARH |
8224014667
dratuljindal@gmail.com |
| Dr Vinayan K P |
Amrita Institute of Medical Sciences & Research Center |
Department of neurology, AIMS Ponekkara P.O,Kochi-682041
Kozhikode
KERALA |
9447800303
vinayankp@aims.amrita.edu |
| Dr Amarjeet Wagh |
Central India Cardiology Hospital and Research institute |
Department of neurology, Plot No. 1, Pioneer Co-op. Housung society, Gawande lay, Khamla Ring road. Opp Sawarkar Garden, Khamla, Nagpur-440015
Nagpur
MAHARASHTRA |
7776871744
amarjeet.wagh2001@gmail.com |
| Dr Neeraj Baheti |
CIIMS |
Department of neurology, 88.2, Bajaj Nagar,Nagpur, Maharashtra-440010
Nagpur
MAHARASHTRA |
9325428259
neerajbaheti@hotmail.com |
| Dr Anaita Udmadia Hegde |
Jaslok Hospital and Research Centre |
Department of neurology,15, Dr. G. Deshmukh
Marg Mumbai Mumbai City
Maharashtra – 400026.
Mumbai
MAHARASHTRA |
9820186155
9820186155
anaitahegde@gmail.com |
| Dr Ritesh Shah |
Saachi Children Hospital |
Department of neurology, Saachi Children Hospital, Near Aakashganga Apartment, Kapadia Health Care, Majuragate, Surat, Gujrat
Ahmadabad
GUJARAT |
9913187560
drriteshcshah@yahoo.co.in |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee Jaslok Hospital Research Centre |
Approved |
| Ethics committee, Unique Hospital |
Approved |
| INSTITUTE ETHICS COMMITTEE,AIIMS |
Approved |
| Institutional Ethics Committee Rughwani Child Care Centre and Hospital |
Approved |
| Institutional Ethics Committee Rughwani Child Care Centre and Hospital |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE; Amrita Institute of Medical Sciences & Research Center |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G408||Other epilepsy and recurrent seizures, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
EPX-100 (Clemizole Hydrochloride) |
EPX-100 will be administered as an oral solution (5 mg/mL). Taste and color-matching placebo
will be administered as an oral solution. Study drug will be administered daily in two divided doses
(BID), 12 ± 2 hours apart. Study drug may be administered by mouth or tube. |
| Comparator Agent |
Placebo |
EPX-100 will be given as
an oral solution (5 mg/mL) up to a maximum of 80 mg BID (160 mg total daily dose). Taste and
color-matching placebo will be administered as an oral solution. Study drug will be administered
daily. The total starting dose of study drug (EPX-100 or PBO) will be calculated based on body
weight and will be given in two divided doses (BID), 12 ± 2 hours apart. |
|
|
Inclusion Criteria
|
| Age From |
2.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
Male and female participants 2 years and older at time of consent.
2. Participant or parent/Legally Authorized Representative (LAR) willing and able to provide
written informed consent, assent (if applicable) prior to initiation of any study related
procedures.
3. Clinical diagnosis of Dravet Syndrome. Participants must have seizures which are not
completely controlled by AEDs with the following criteria:
• Onset of seizures prior to 18 months of age,
• Normal development at onset,
• History of seizures that are generalized, unilateral clonic, and/or hemiclonic,
• Brain MRI without cortical malformation (not including mild atrophy associated with the
natural progression of Dravet Syndrome), and
• Genetic mutation of the SCN1A gene must be documented.
4. The participant must be approved to participate by the Independent Reviewer, in
collaboration with the PI. Participants will be approved for participation following review of
the participant’s medical and seizure history, historical neuroimaging, historical EEGs,
genetic report confirming SCN1A mutation, and review and classification of at least 28 days
of baseline seizures.
5. ≥4 countable convulsive seizures within minimum 28-day screening/baseline period (e.g.,
hemiclonic, secondarily generalized tonic-clonic, generalized tonic-clonic, tonic, clonic,
tonic/atonic (resulting in a drop), or focal with clear observable motor signs).
6. Participants should be on a stable regimen of AEDs ≥30 days prior to Visit 1 and generally
in good health.
7. Participant or parent/ LAR is able and willing to maintain an accurate and complete daily
seizure and medication diary for the duration of the trial.
8. Sexually active women of child-bearing potential (WCBP) must be using a medically
acceptable method of birth control and have a negative serum or urine pregnancy test at the
screening (Visit 1) and Randomization (Visit 2). A WCBP is defined as a female who is
biologically capable of becoming pregnant. A medically acceptable method of birth control
includes intrauterine devices in place for at least 3 months, surgical sterilization, or adequate
barrier methods (e.g., diaphragm and foam). Use of oral contraceptives in combination with
another method (e.g., a spermicidal cream) is acceptable. In participants who are not sexually
active, abstinence is an acceptable form of birth control and urine will be tested per protocol.
Women who are of nonchild-bearing potential, i.e., post-menopause, must have this
condition captured in their medical history. Pregnant women are excluded from this study |
|
| ExclusionCriteria |
| Details |
Known sensitivity, allergy, or previous exposure to EPX-100 (Clemizole HCl).
2. Exposure to any investigational drug or device <90 days prior to screening or plans to
participate in another drug or device trial at any time during the study.
3. Seizures secondary to illicit drug or alcohol use, infection, neoplasm, demyelinating disease,
degenerative neurological disease, or CNS disease deemed progressive, metabolic illness, or
progressive degenerative disease.
4. Concurrent use of drugs known to interfere with EPX-100, including moderate or severe
inducers or inhibitors of CYP3A4/5/7. Specifically, concurrent use of carbamazepine,
oxcarbazepine, and/or phenytoin, as well as refraining from grapefruits and grapefruit juice
during the study period. A list of CYP3A4/5/7 inhibitors and inducers is included in
Appendix 1.
5. Prior or concurrent use of or lorcaserin.
6. Concurrent use of fenfluramine. Participants with prior use of fenfluramine within the
previous 3 months, or without proper documentation of an echocardiogram, at minimum 3
months following the last dose of fenfluramine, to ensure that the participant does not meet
any criteria for drug-related (fenfluramine) valvular heart disease and/or drug-related
pulmonary arterial hypertension (PAH) as indicated by any of the following:
• documented mild or greater aortic regurgitation [AR] or moderate or greater mitral
regurgitation [MR]
• significant (greater than mild) tricuspid regurgitation
• abnormally thickened cardiac valve and/or has restricted motion of the valve leaflets
• elevated right heart/pulmonary artery pressure >35mmHg
7. Has any medical condition that, in the PI’s judgment, is considered to be clinically significant
and could potentially affect participant safety or study outcome, including but not limited to:
clinically significant cardiac disease (including angina, congestive heart failure, uncontrolled
hypertension, and history of arrhythmias), renal, pulmonary, gastrointestinal, hematologic or
hepatic conditions; or a condition that affects the absorption, distribution, metabolism, or
excretion of drugs.
8. Has an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months
or a suicide attempt in the past 3 years.
|
|
|
Method of Generating Random Sequence
|
Adaptive randomization, such as minimization |
|
Method of Concealment
|
Alternation |
|
Blinding/Masking
|
Double Blind Double Dummy |
|
Primary Outcome
|
| Outcome |
TimePoints |
To evaluate the efficacy of EPX-100
compared with placebo as adjunctive
therapy in children and adult participants
with Dravet Syndrome, in terms of the
mean percent change in countable
convulsive seizure frequency (CCSF1
) in
the Titration and Maintenance T plus M
periods relative to baseline |
The following assessment will be performed for the evaluation of the secondary efficacy
endpoints, also described in Section 4:
- Clinical Global Impression: Clinician (CGI-C).
- Clinical Global Impression: Participant/Caregiver (CGI-P; Appendix 3; Busner and
Targum, 2007).
- Quality of Life in Childhood Epilepsy (QOLCE-55; Appendix 4; Conway et al., 2017,
Goodwin et al., 2015).
- Seizure Severity using Hague Seizure Severity Scale (HASS). Sleep Disturbance |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To describe the difference between EPX 100 vs placebo in the number of
countable convulsive seizure free days in
the T plus M periods relative to baseline |
The number of countable convulsive
seizure free days in the T plus M period
relative to baseline |
|
|
Target Sample Size
|
Total Sample Size="100"
Sample Size from India="20"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
08/05/2023 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/09/2020 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
Modification(s)
|
Years="3"
Months="4"
Days="12" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Not Yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Following screening and after establishing baseline seizure frequency during a 4-week
Screening/Baseline period (Day -28–0), qualifying participants who meet all inclusion and
exclusion criteria will enter the study and be randomized 1:1 to EPX-100 or placebo.Participants will receive their first dose of study drug in the clinic following randomization
(Visit 2). The total daily starting dose of study drug (EPX-100 or PBO) will be calculated
based on body weight and will be given in two divided doses (BID).
Participants requiring titration (weighing less than 80 Kg) will be dosed in increments of
1.0 mg/kg BID every 7-days until they reach the maximum 4.0 mg/kg BID dose. The
maximum daily dose is 80 mg BID; therefore, participants should not be titrated past a dose of
80 mg BID. Once the maximum dose has been achieved, participants must remain on that dose
for the remaining days of the 4-week titration period.
Participants that do not require titration (i.e., weighing ≥ 80 kg) will receive the maximum dose
of 80 mg BID for the full 4-weeks.
At the discretion of the Principal Investigator (PI), any participants who are unable to tolerate a
starting dose of 1.0 mg/kg BID may initiate titration at a starting dose of 0.5 mg/kg BID for the
first 7 days and increase by 0.5 mg/kg BID every 7 days until they reach the maximum dose
tolerated (not to exceed 80 mg/BID).
All doses will be blinded; subjects on EPX-100 or PBO will undergo the same titration.
Participants randomized to PBO will undergo a mock titration to ensure the blind is maintained. |