Niemann-Pick Disease type C (NPC) MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: N Acetyl L Leucine
Product Code: IB1001
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: N Acetyl L leucine
Sponsors
IntraBio Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent signed by the patient and/or their legal representative/ parent 2.Male or female aged =6 years in Europe OR =18 years in the United States with a confirmed diagnosis of NPC at the time of signing informed consent. Confirmed diagnosis includes [Patterson et al. 2017]: a)Clinical features and positive biomarker screen and/or filipin test without genetic tests results (has not been performed). b)Clinical features and positive genetic test c)Clinical features and positive biomarker screen and/or filipin test but only one NPC mutation identified on genetic test d)Clinical features with positive biomarker screen and/or filipin test and positive genetic test 3.Females of childbearing potential, defined as a premenopausal female capable of becoming pregnant, will be included if they are either sexually inactive (sexually abstinent for 14 days prior to the first dose and confirm to continue through 28 days after the last dose) or using one of the following highly effective contraceptives (i.e. results in <1% failure rate when used consistently and correctly) 14 days prior to the first dose continuing through 28 days after the last dose: a)intrauterine device (IUD); b)surgical sterilization of the partner (vasectomy for 6 months minimum); c)combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal); d)progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable); e)intrauterine hormone releasing system (IUS); f)bilateral tubal occlusion. 4.Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to the first dose: a)hysteroscopic sterilization; b)bilateral tubal ligation or bilateral salpingectomy; c)hysterectomy; d)bilateral oophorectomy; OR be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status. FSH analysis for postmenopausal women will be done at screening. FSH levels should be in the postmenopausal range as determined by the central laboratory. 5.Non-vasectomized male patient agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication and the female partner agrees to comply with inclusion criteria 3 or 4. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male. 6.If male, patient agrees not to donate sperm from the first dose until 90 days after dosing. 7.Patients must fall within: a)A SARA score of 5 = X = 33 points (out of 40) AND i.Within the 2-7 range (out of 0-8 range) of the Gait subtest of the SARA scale OR ii.Be able to perform the 9 Hole Peg T
Exclusion criteria
Exclusion criteria: Individuals who meet any of the following criteria are not eligible to participate in the study: 1.Asymptomatic patients 2.Patient has clinical features of NPC and a positive biomarker screen and/or filipin test, but a completely negative result on a previous genetic test for NPC 3.Patients who have any of the following: a)Chronic diarrhea; b)Unexplained visual loss; c)Malignancies; d)Insulin-dependent diabetes mellitus. e)Known history of hypersensitivity to the N-Acetyl-D-Leucine (DL-, L-, D-) or derivatives. f)History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose, sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan, dimethicone, methylparaben, and potassium sorbate). 4.Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; ‘study drug’) within 6 weeks prior to Visit 1. 5.Patients with a physical or psychiatric condition which, at the investigator’s discretion, may put the patient at risk, may confound the study results, or may interfere with the patient’s participation in the clinical study. 6.Known clinically-significant (at the discretion of the investigator) laboratories in hematology, coagulation, clinical chemistry, or urinalysis, including, but not limited to: a.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN); b.Total bilirubin >1.5x ULN, unless Gilbert’s syndrome is present in which case total bilirubin >2x ULN. 7.Known or persistent use, misuse, or dependency of medication, drugs, or alcohol. 8.Current or planned pregnancy or women who are breastfeeding. 9.Patients with severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that, at the investigator’s discretion, interferes with their ability to perform study assessments. 10.Patients who have been diagnosed with arthritis or other musculoskeletal disorders affecting joints, muscles, ligaments, and/or nerves that by themselves affects patient’s mobility and, at the investigator’s discretion, interferes with their ability to perform study assessments. 11.Patients unwilling and/or not able to undergo a 6-week washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6. a)Aminopyridines (including sustained-release form); b)N-Acetyl-DL-Leucine (e.g. Tanganil®); c)N-Acetyl-L-Leucine (prohibited if not provided as IMP); d)Riluzole; e)Gabapentin; f)Varenicline; g)Chlorzoxazone; h)Sulfasalazine; i)Rosuvastatin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on blinded raters’ clinical impression of change in severity (CI-CS) in the treatment of NPC.; Secondary Objective: To assess the clinical efficacy of N-Acetyl-L-Leucine on symptoms of ataxia, functioning, and quality of life for patients with NPC; To evaluate the safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in patients with NPC, including patients aged =18 years in the United States and patients aged =13 years in Europe, and weight-tiered doses in patients 6 - 12 years of age in Europe ; Primary end point(s): The primary endpoint for the study is based on blinded raters’ Clinical Impression of Change in Severity (CI-CS) comparing videos showing the patient’s change in performance over 6 weeks on a pre-defined anchor clinical symptom scale: either the 9 Hole Peg Test of the Dominant Hand (9HPT-D) or the 8 Meter Walk Test (8MWT). The comparison of the Visit 4 video with the Visit 2 video and the comparison of the Visit 6 video with the Visit 4 video will provide the scores that contribute to the primary endpoint. Each of these comparisons will score improvement on a 7-point Likert scale (+3=significantly improved to -3= significantly worse). During the pre-treatment period, the treating physician will evaluate each patient’s clinical symptoms and select at Visit 1 either the 9HPT-D or 8MWT as the primary anchor around which the CI-CS assessment will be scored. A cognitive assessment should be performed at Visit 1 according to standard procedures of the clinical site to assist with the selection of the anchoring functional test appropriate for each patient from both a cognitive and a motor perspective. The primary evaluation of the CI-CS will be performed by two independent neurologists whose assessments will be based on videos of the anchor test taken at e | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline (Day 1) to end of treatment with IB1001 (Approximately Day 42); End of treatment with IB1001 (Approximately Day 42) to the end of post-treatment washout (Approximately Day 84); Secondary end point(s): •Spinocerebellar Ataxia Functional Index (SCAFI) •Scale for Assessment and Rating of Ataxia (SARA) score •Quality of Life EQ-5D-5L for patients aged =18; EQ-5D-Y for patients aged <18 years (visual analogue scale; descriptive system) •Modified Disability Rating Scale (mDRS) •Treating Physician Clinical Global Impression of Severity (CGI-S) at every visit •Treating Physician Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) •Caregiver Clinical Global Impression of Severity (CGI-S) at every visit •Caregiver Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) •Patient Clinical Global Impression Scales Impression of Severity (CGI-S) at every visit if they are able •Patient Clinical Global Impression of Change (CGI-C) comparing end of treatment (Visit 4) to baseline (Visit 2), and end of washout (Visit 6) to end of treatment (Visit 4) if they are able | — |
Countries
Germany, Slovakia, Spain, United Kingdom, United States
Contacts
Public ContactTaylor Fields
IntraBio Ltd
Outcome results
None listed