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: Granules for oral suspension in sachet
INN or Proposed INN: N Acetyl L leucine
Current Sponsor code: IB1001
Other descriptive
Sponsors
IntraBio Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Individuals who meet all of the following criteria are eligible to participate in the study: 1. Written informed consent signed by the patient and/or their legal representative/ parent/ impartial witness 2. Male or female aged =4 years with a confirmed diagnosis of NPC at the time of signing informed consent. Confirmed diagnosis includes one of the following [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 who have undergone one of the following sterilization procedures at least 6 months prior to the first dose: a) hysteroscopic sterilization; b) 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 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 their last dose. 7. Patients must fall within: a) A SARA score of 7 = X = 34 points (out of 40) AND b) Either: i. Within the 2-7 range (0-8 range) of the Gait subtest of the SARA scale OR ii. Be able to perform the 9-Hole Peg Test with Dominant Hand (9HPT-D) (SCAFI subtest) in 20 = X =150 seconds. 8. Weight =15 kg at screening. 9. Patients are willing to disclose their existing medications/therapies for (the symptoms) of NPC, including those on the prohibited medication list. Non-prohibited medications/therapies (authorized medicines for NPC [e.g. miglustat], speech thera
Exclusion criteria
Exclusion criteria: Individuals who meet any of the following criteria are not eligible to participate in the study: 1. Patients who have any known hypersensitivity or history of hypersensitivity to: a. Acetyl-Leucine (DL-, L-, D-) or derivatives. b. Excipients the IB1001 sachet (namely isomalt, Hypromellose, and Strawberry Flavour). c. Excipients the placebo sachet (namely isomalt, Hypromellose, Strawberry Flavour, Citric acide, microcrystalline cellulose, lactose, denatonium benzoate). 2. Simultaneous participation in another clinical study or participation in any clinical study involving administration of an investigational medicinal product (IMP; ‘study drug’) for at least 42 days prior to Visit 1. At the discretion of the investigator, Medical Monitor, and Sponsor, the washout period for specific IMPs may be longer based on the pharmacological activity and pharmacokinetics of the drug. 3. Patients with a physical or psychiatric condition which, at the investigator’s discretion and in consultation with the Medical Monitor and Sponsor (as applicable), may put the patient at risk, may confound the study results, or may interfere with the patient’s participation in the clinical study, i.e. reliably perform study assessments. 4. Known or persistent use, misuse, or dependency of medication, drugs, or alcohol. 5. Current or planned pregnancy or women who are breastfeeding. 6. 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. 7. 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. 8. Patients unwilling and/or not able to undergo a 42-day washout period from any of the following prohibited medication prior to Visit 1 (Baseline 1) and remain without prohibited medication through Visit 6. a) N-Acetyl-DL-Leucine (e.g. Tanganil®); b) N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-301 trial); c) Sulfasalazine; d) Rosuvastatin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of N-acetyl-L-leucine based on the Scale for the Assessment and Rating of Ataxia (SARA) for the chronic treatment of NPC. For the extension phase, the primary objective is to evaluate the efficacy of N-Acetyl-L-Leucine based on the 5-domain Niemann-pick disease type c clinical severity scale (NPC-CSS);Secondary Objective: o To assess the clinical efficacy of N-Acetyl-L-Leucine on symptoms, functioning, and quality of life for patients with NPC; o To evaluate the safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in NPC patients aged =13 years, and weight-tiered doses in NPC patients aged 4 to 12 years of age In the extension phase, the secondary objectives are to: oTo evaluate the long-term safety and tolerability of N-Acetyl-L-Leucine at 4 g/day in patients aged =13 years, and weight-tiered doses in patients 4 to 12 years of age, with NPC oTo characterize the pharmacokinetics (PK) of N-Acetyl-L-Leucine in patients with NPC Exploratory objective: oTo assess the clinical efficacy of long-term treatment with N-Acetyl-L-Leucine on symptoms, functioning, and quality of life for patients with NPC ;Primary end point(s): The primary endpoint is the Scale for the Assessment and Rating of Ataxia (SARA) [Schmitz-Hübsch et al, 2006; Subramony, 2007] is an eight-item clinical rating scale (range 0–40, where 0 is the best neurological status and 40 the worst). It is a reliable and valid clinical scale with a high internal consistency that measures the severity of symptoms and ataxia and increases with ataxia disease stage.;Timepoint(s) of evaluation of this end point: The primary endpoint is based on the analysis of covariance comparing the mean SARA at the end of Period I (Visit 4) minus the mean SARA at the end of Period II (Visit 6 with the Baseline SARA (Visit 2) as a covariate. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Spinocerebellar Ataxia Functional Index (SCAFI) • Quality of Life EQ-5D-5L for patients aged =18; EQ-5D-Y for patients aged <18 years • Modified Disability Rating Scale (mDRS) • Physician’s, Caregiver’s, and Patient’s (if able) Clinical Global Impression of Improvement (CGI-I) comparing end of period I (Visit 4) to baseline (Visit 2), and end of period II (Visit 6) to end of period I (Visit 4) ;Timepoint(s) of evaluation of this end point: The change from Visit 4 (end of period I) to Visit 6 (end of period II) | — |
Countries
Australia, Czechia, Czech Republic, Germany, Netherlands, Slovakia, Switzerland, United Kingdom, United States
Contacts
Public ContactTaylor Fields
IntraBio Ltd
Outcome results
None listed