Clinical trial NCT03976076: A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients
Official title: A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, and Pharmacokinetics of Orally Administered JBPOS0101 for Refractory Infantile Spasms Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Refractory Infantile Spasms
Keywords: JBPOS0101
Infantile Spasms
Electroencephalogram
Lead sponsor: Bio-Pharm Solutions Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-05
Enrollment: 16
Sex: ALL
Minimum age (years): 6
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients received the investigational product at a dose of 6 milligram per kg orally twice daily; once in the morning and 12 hours following the morning dose during the first 7 days of Treatment Period 1. Starting from the PM dose on the day of Visit 3, the dose was escalated and patients received the investigational product at a dose of 9 mg/kg orally twice daily. Starting on Day 15, the dose was escalated again and patients received the investigational product at a dose of 15 mg/kg orally twice daily until the end of Treatment Period 1 (Day 28).
Primary purpose: TREATMENT

Brief summary: A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, and pharmacokinetics of Orally Administered JBPOS0101 for Refractory Infantile Spasms Patients.

Detailed description: This open label, multicenter study allowed JBPOS0101 (investigational product) to be given as either add-on therapy or monotherapy for patients with refractory infantile spasms. The design and choice of study population of this Phase 2 clinical study was based on the need to provide initial safety, tolerability, pharmacokinetics (PK), and efficacy outcomes of the investigational product for future clinical studies.

Eligibility criteria: Inclusion Criteria:

* Male or female between 6 months through 36 months of age at the time of informed consent
* Had clinical diagnosis of Infantile spasms (IS), confirmed by video-electroencephalogram (EEG) analysis, and hypsarrhythmia on EEG at screening according to the Burden of Amplitudes and Epileptiform Discharges (BASED) scale score.
* As assessed by the investigator had no or partial response to at least 2 out of the 3 therapies of adrenocorticotrophic hormone (ACTH), vigabatrin, and glucocorticoids (i.e. prednisolone), or had no or partial response to at least 1 out of the 3 therapies of ACTH, vigabatrin, and glucocorticoids and was contraindicated to and/or refused by the patient's legal representative(s) for treatment with one or both other 2 therapies.
* Patient had general good health (defined as the absence of any clinically relevant abnormalities as determined by the investigator) based on physical and neurological examinations, medical history, normal renal function and electrocardiogram (ECG), and clinical laboratory values completed during the Screening Period visit (Visit 1).
* Parent(s)/caregiver(s) were willing and able to comply with the study procedures and visit schedules in the opinion of the investigator.
* Parent(s)/caregiver(s) fully comprehend and sign the ICF in accordance with applicable laws, regulations, and local requirements, understand all study procedures, and can communicate satisfactorily with the investigator and study coordinator.

Exclusion Criteria:

* Patient considered by the investigator, for any reason (including, but not limited to, the risks described as precautions and warnings in the current version of the investigator's brochure for investigational product) to be an unsuitable candidate to receive the investigational product.
* Patient had known or suspected allergy to the investigational product or apple juice.
* Patient had clinically significant renal impairment, defined as creatinine \>1.5 mg/dL or blood urea nitrogen \>2 × upper limit of normal (ULN);
* Clinically significant liver dysfunction, defined as total bilirubin ≥2 × ULN, or aspartate aminotransferase or alanine aminotransferase ≥3 × ULN;
* Patient had clinically significant abnormal laboratory values; the investigator may deem the patient eligible if he/she judges the laboratory values to be not clinically significant.
* Patient had an ongoing or known history of human immunodeficiency virus infection, or chronic hepatitis B or C.
* Patient had a clinically significant abnormality on ECG that, in the opinion of the investigator, increases the safety risks of participating in the study.
* Patient had a neurodegenerative disorder as the underlying cause of IS.
* Patient had a known history of aspiration pneumonia within the past year.
* Patient had previously participated in another clinical study of the investigational product or received any investigational drug or device or investigational therapy within 30 days of study entry.
* Patient had received therapy with felbamate, cannabinoids, ketogenic diet or vagus nerve stimulation within 14 days of screening.
* Patient had received therapy with a medication known to be a CYP3A4 substrate and whose PK had been shown to be impacted in the presence of a CYP3A4 inhibitor within 14 days of screening.
* Patient had not remained at stables doses of all drugs used for treating epileptic seizures for at least 14 days prior to screening (except for rescue medications used for acute treatment of breakthrough seizures which were not known to be CYP3A4 substrates and whose PK had not been shown to be impacted in the presence of a CYP3A4 inhibitor.
* Patient had a lethal or potentially lethal condition other than infantile spasms, with a significant risk of death before 18 months of age such as non-ketotic hyperglycinemia.
* Patient had a body weight below 5 kg.
* Patient had an underlying metabolic disease associated with glucose intolerance (e.g., glucose transporter deficiencies).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 to Day 56
Secondary outcomes:
measure: JBPOS0101 Plasma Concentration 0.5 - 1.5 Hours Post Morning Dose, Day 1
timeFrame: 0.5 to1.5 hours post morning (AM) dose on Day 1
measure: JBPOS0101 Plasma Concentration 4-6 Hours Post Morning Dose, Day 1
timeFrame: 4 to 6 hours post morning (AM) dose on Day 1
measure: JBPOS0101 Plasma Concentration 8 Hours Post Morning Dose and Pre-PM Dose, Day 1
timeFrame: 8 hours post morning (AM) dose and pre-PM dose on Day 1
measure: JBPOS0101 Plasma Concentration 0.5 -1.5 Hours Post Morning Dose, Day 21
timeFrame: 0.5 to1.5 hours post morning (AM) dose on Day 21
measure: JBPOS0101 Plasma Concentration 4 - 6 Hours Post Morning Dose, Day 21
timeFrame: 4 to 6 hours post morning (AM) dose on Day 21
measure: JBPOS0101 Plasma Concentration 8 Hours Post Morning Dose and Pre-PM Dose, Day 21
timeFrame: 8 hours post morning (AM) dose and pre-PM dose on Day 21
measure: JBPOS0101 Urine Concentration at Day 1
timeFrame: Day 1
measure: JBPOS0101 Urine Concentrations at Day 21
timeFrame: Day 21
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital LA
state: California
city: Los Angeles
country: United States
facility: UCLA - David Geffen School of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Epilepsy Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Winter Park
country: United States
facility: Pediatric Neurology, PA
state: Florida
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
city: Louisville
country: United States
facility: University of Louisville School of Medicine
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Tacoma
country: United States
facility: Multicare Institute for Research and Innovation
state: Washington
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital (KNUH)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Bio-Pharm Solutions
name: Hee Jin Kim
role: STUDY_DIRECTOR
References: