A Study of Orally Administered JBPOS0101 in Refractory Infantile Spasms Patients

A Phase 2 Study to Assess the Safety, Tolerability, Exploratory Efficacy, and Pharmacokinetics of Orally Administered JBPOS0101 for Refractory Infantile Spasms Patients

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

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.

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).

During Treatment Period 1, the IP was administered at 6 mg/kg, per oral (PO), twice a day (BID), 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 Visit 3, the dose was escalated and patients received the Investigational Product (JBPOS0101) (IP) at a dose of 9 mg/kg orally BID. Starting on Day 15, the dose was escalated again and patients received the IP at a dose of 15 mg/kg orally BID until the end of Treatment Period 1 (Day 28). Each dose of the IP was administered after at least a 2-hour fast. Food was given 2 hours after dosing.

TEAEs were defined as any event that did not present before exposure to the investigational product (IP) or any event already present that worsened in either intensity or frequency after exposure to the IP.

Pharmacokinetics: JBPOS0101 plasma concentration 8 hours post morning dose and pre-PM dose on Day 21.

Pharmacokinetics: JBPOS0101 urine concentration on Day 1. Urine samples were collected following the morning dose.

Pharmacokinetics: JBPOS0101 urine concentration on Day 21. Urine samples were collected following the morning dose.

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).