A 20-Week Multicenter, Randomized, Double-Blind, Placebo Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children and Adult Participants withDravet Syndrome (ARGUS Trial)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 100
- 试验地点
- 6
- 主要终点
- To evaluate the efficacy of EPX-100
研究概览
简要总结
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 doseof 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Adaptive randomization, such as minimization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 2.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and female participants 2 years and older at time of consent.
- •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.
- •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.
- •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.
- •â‰¥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).
- •Participants should be on a stable regimen of AEDs ≥30 days prior to Visit 1 and generally in good health.
- •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.
- •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.
排除标准
- •Known sensitivity, allergy, or previous exposure to EPX-100 (Clemizole HCl).
- •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.
- •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.
- •Concurrent use of drugs known to interfere with EPX-100, including moderate or severe inducers or inhibitors of CYP3A4/5/
- •A list of CYP3A4/5/7 inhibitors and inducers is included in Appendix
- •Prior or concurrent use of or lorcaserin.
- •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
- •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.
- •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.
结局指标
主要结局
To evaluate the efficacy of EPX-100
时间窗: 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
compared with placebo as adjunctive
时间窗: 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
therapy in children and adult participants
时间窗: 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
with Dravet Syndrome, in terms of the
时间窗: 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
mean percent change in countable
时间窗: 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
convulsive seizure frequency (CCSF1
时间窗: 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
) in
时间窗: 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
the Titration and Maintenance T plus M
时间窗: 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
periods relative to baseline
时间窗: 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
次要结局
- To describe the difference between EPX 100 vs placebo in the number of(countable convulsive seizure free days in)