Effects of N-Acetyl-L-Leucine on Niemann-Pick disease type C (NPC): A Phase III, randomized, placebo-controlled, double-blind, crossover study
- Conditions
- Hereditary metabolic diseaseNPC10021605
- Registration Number
- NL-OMON53762
- Lead Sponsor
- IntraBio Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
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 on 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
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>In Europe and Australia, the primary endpoint is the Scale for the Assessment<br /><br>and Rating of Ataxia (SARA). SARA is an eight-item clinical rating scale (range<br /><br>0-40, where 0 is the best neurological status and 40 the worst). It is a<br /><br>reliable and valid clinical scale with a high internal consistency that<br /><br>measures the severity of ataxia and increases with ataxia disease stage.<br /><br>In the United States (US), the primary endpoint is the modified Scale for the<br /><br>Assessment and Rating of Ataxia (mSARA). The mSARA is a six-item clinical<br /><br>rating scale (range 0-30, where 0 is the best neurological status and 30 the<br /><br>worst).<br /><br>The primary endpoint is defined as the total SARA / mSARA value at the end of<br /><br>Period I (Visit 4) versus the end of Period II (Visit 6).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>The following secondary assessments will be evaluated:<br /><br>• Spinocerebellar Ataxia Functional Index (SCAFI)<br /><br>• SARA (key secondary endpoint - US only)<br /><br>• Quality of Life EQ-5D-5L for patients aged >=18; EQ-5D-Y for children aged <18<br /><br>years<br /><br>• Modified Disability Rating Scale (mDRS)<br /><br>• Treating Physician*s, Caregiver*s (if applicable) and Patient*s (if able)<br /><br>Clinical Global Impression of Improvement (CGI-I)<br /><br><br /><br><br /><br>Exploratory Endpoints:<br /><br>• Sparse PK sampling will be collected to characterize the PK of<br /><br>N-Acetyl-L-Leucine in patients with NPC<br /><br>• Modified SARA (Europe/ Australia only)<br /><br>• Niemann-Pick disease type C Clinical Severity Scale (NPC-CSS)<br /><br>• 5-domain NPC-CSS<br /><br>• Treating Physician*s, Caregiver*s (if applicable), and Patient*s (if able)<br /><br>Clinical Global Impression of Severity (CGI-S</p><br>