To demonstrate that N-Acetyl-L-Leucine is effective in improving symptoms, functioning and quality of life in patients with Niemann-Pick Type C disease (NPC).
- Conditions
- To demonstrate that N-Acetyl-L-Leucine is effective in improvingsymptoms, functioning, and quality of life in patients withNiemann-Pick Type C disease (NPC).MedDRA version: 20.0Level: PTClassification code 10029403Term: Niemann-Pick diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-004331-71-GB
- Lead Sponsor
- IntraBio Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 33
Inclusion Criteria:
1. Written informed consent signed by the patient and/or their legal representative/ parent/impartial witness
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 abstinent22 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 their last dose.
7. Patients must fall within:
a) A SARA score of 5 = X = 33 points (out of 40) AND
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 (e.g. miglustat, concomitant speech therapy, and physiotherapy)
A patient will not be included in this study if one or more of the following criteria apply:
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:
g) Chronic diarrhea;
h) Unexplained visual loss;
i) Malignancies;
j) Insulin-dependent diabetes mellitus.
k) Known history of hypersensitivity to Acetyl-Leucine (DL-, L-, D-) or derivatives.
l) History of known hypersensitivity to excipients of Ora-Blend® (namely sucrose,
sorbitol, cellulose, carboxymethylcellulose, xanthan gum, carrageenan,
dimethiconne, 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 haematology, 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 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.
j) Aminopyridines (including sustained-release form);
k) N-Acetyl-DL-Leucine (e.g. Tanganil®);
l) N-Acetyl-L-Leucine (prohibited if not provided as IMP);
m) Riluzole;
n) Gabapentin;
o) Varenicline;
p) Chlorzoxazone;
q) Sulfasalazine;
r) Rosuvastatin.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method