Effects of N-Acetyl-L-Leucine in Niemann-Pick Disease Type C (NPC): A randomized, placebo-controlled, double-blind, phase III study
Zusammenfassung der Studie
The purpose of this study is to determine whether the investigational drug N-Acetyl-L-Leucine (« IB1001 »), after a 12-week treatment compared to a 12-week treatment with a placebo, can help with symptoms of NPC, such as ataxia (disorder of coordinated movement). A placebo looks like a medication but contains no active ingredient, allowing for a better assessment of the effects and side effects of a new drug compared to the placebo. The study is divided into 3 study phases: 1. Pre-study (“Baseline”): This period includes 2 visits to the study center. Visit 2 is scheduled approximately 14 (up to 21 days) after visit 1. During this pre-study phase, you will not receive any investigational drug yet. Randomization: At visit 2, you will be randomly assigned to one of the two sequences of the investigational drug (either first IB1001, then placebo or first placebo, then IB1001). 2. Period I: Period I includes 2 visits to the investigational center. You will receive the investigational drug (IB1001 or placebo) during this period for 84-91 days. 3. Period II: After completing Period I, you will immediately begin Period II. At the start of Period II, you will switch to the other investigational drug (i.e., if you received IB1001, you will now receive placebo, if you received placebo, you will now receive IB1001). Period II includes at least 2 visits to the investigational center and lasts 84-91 days. At the end of the study, you will be offered the opportunity to participate in a planned open-label extension phase if your study doctor believes that further treatment with IB1001 would be in your best interest. In all study phases, examinations will be conducted to check your health status and the effect of the study drug. This includes blood samples, urine samples, ECGs, and filling out some questionnaires. For some patients, an additional introductory phase may be necessary if they are taking prohibited medications.
(BASEC)
Untersuchte Intervention
At the pre-study, you will be asked to read and sign an informed consent form. Then, your medical history, concomitant medications, and health status will be collected.
During the pre-study and periods I and II, the following examinations will be conducted:
- Physical examination - including examination of your general appearance, head and neck, eyes and ears, nose and throat, lungs, heart, gastrointestinal tract, muscles and bones, as well as a neurological examination.
- Vital signs will be measured (blood pressure, heart rate, weight, and height)
- Blood draws - several tubes of blood will be drawn for testing.
- Urine samples - urine samples will be collected for testing.
- ECGs - ECGs will be performed to record your heart's activity to ensure that your heart is functioning normally.
- Questionnaires - You will be asked to fill out some questionnaires on the following points:
o Your quality of life
o Clinical global assessment of severity - In this questionnaire, you will be asked how you feel at this moment.
o Clinical global assessment of change - In this questionnaire, you will be asked whether your condition has changed since the start/change of the study drug.
To assess NPC, several tests will be conducted:
An 8-meter walk test - You will be asked to walk 8 meters as quickly as possible
The “9-Hole Peg Test” - You will be asked to place 9 pegs into 9 holes on a board and then remove the pegs as quickly as possible
The “PATA” test - To measure your speech performance, you will be asked to repeat “PATA-PATA-PATA…” as quickly as possible
o Scale for assessment and rating of ataxia (SARA) - A clinical rating scale with eight points that assesses gait, posture, sitting, speech, fine motor skills, and ataxia.
o Modified disability rating scale - The study doctor will assess your overall neurological status in relation to your NPC.
o Niemann-Pick Disease Type C clinical severity scale (NPC-CSS) - The study doctor will assess your overall neurological status (how your nervous system processes things to move body parts, or sensations/senses like pain or warmth) in relation to your NPC. This also includes assessing your walking, eye movements, speech, swallowing, and how you move your hands.
(BASEC)
Untersuchte Krankheit(en)
Niemann-Pick Disease Type C
(BASEC)
1. Written informed consent, signed by the patient and/or their legal representative/a parent/an impartial witness 2. Men or women aged ≥ 4 years with a confirmed NPC diagnosis at the time of signing the informed consent, and containing the following: a) A SARA assessment within the desired range, confirmed by the study doctor AND b) Either: i. being in the range 2 - 7 (range from 0 - 8) on the gait subtest of the SARA scale OR ii. being able to perform the 9-hole peg test with the dominant hand within the target time, as confirmed by the study doctor. (BASEC)
Ausschlusskriterien
1. Simultaneous participation in another clinical study or participation in any clinical study in which the investigational drug was administered within 42 days prior to visit 1. At the discretion of the investigator, medical monitor, and sponsor, patients who have received other investigational drugs may still participate in the study if those medications are discontinued for an appropriate period before the start of this study. 2. Patients whose physical, cognitive, or psychological condition, at the discretion of the investigator and in consultation with the medical monitor and (if applicable) sponsor, poses a risk to the patient, the study results, or the patient's participation in the clinical study, i.e., may distort or compromise the reliable conduct of the study. 3. Patients who are not willing and/or able to take a 42-day break from any of the following prohibited medications before the pre-study (“Baseline”) and to remain without prohibited medications until visit 6: a. N-Acetyl-DL-Leucine (e.g., Tanganil®) b. N-Acetyl-L-Leucine (prohibited unless provided as an investigational drug in the IB1001-301 study) c. Sulfasalazine d. Rosuvastatin (BASEC)
Studienstandort
Bern
(BASEC)
Sponsor
IntraBio Ltd., Oxfordshire, UK Stimolo Pharma Consulting GmbH, 3018 Bern, Switzerland
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Dr. med. Tatiana Brémòva-Ertl
+41 31 632 70 00
tatiana.bremova-ertl@clutterinsel.chInselspital Bern
(BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
24.08.2022
(BASEC)
ICTRP Studien-ID
NCT05163288 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Wirkungen von N-Acetyl-L-Leucin bei Morbus Niemann-Pick Typ C: Eine multinationale, randomisierte, Placebo-kontrollierte Doppelblind-Crossover-Studie (BASEC)
Wissenschaftlicher Titel
Effects of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C (NPC): A Phase III, Randomized, Placebo-controlled, Double-blind, Crossover Study (ICTRP)
Öffentlicher Titel
A Pivotal Study of N-Acetyl-L-Leucine on Niemann-Pick Disease Type C (ICTRP)
Untersuchte Krankheit(en)
Niemann-Pick Disease, Type C (ICTRP)
Untersuchte Intervention
Drug: N-Acetyl-L-LeucineOther: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
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 genetic diagnosis of NPC at the time
of signing informed consent.
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:
1. intrauterine device (IUD)
2. surgical sterilization of the partner (vasectomy for 6 months minimum)
3. combined (estrogen or progestogen containing) hormonal contraception associated
with the inhibition of ovulation (either oral, intravaginal, or transdermal)
4. progestogen only hormonal contraception associated with the inhibition of
ovulation (either oral, injectable, or implantable)
5. intrauterine hormone releasing system (IUS)
6. 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:
1. hysteroscopic sterilization
2. bilateral tubal ligation or bilateral salpingectomy
3. hysterectomy
4. 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 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
therapy, and physiotherapy) are permitted provided:
1. The Investigator does not believe the medication/therapy will interfere with
the study protocol/results
2. Patients have been on a stable dose/duration and type of therapy for at least
42 days before Visit 1 (Baseline 1)
3. Patients are willing to maintain a stable dose/do not change their therapy
throughout the duration of the study.
10. An understanding of the implications of study participation, provided in the written
patient information and informed consent by patients or their legal
representative/parent, and demonstrates a willingness to comply with instructions
and attend required study visits (for children this criterion will also be assessed
in parents or appointed guardians).
Exclusion Criteria:
1. Patients who are unable to consistently Patients who have any known hypersensitivity
or history of hypersensitivity to:
1. Acetyl-Leucine (DL-, L-, D-) or derivatives.
2. Excipients the IB1001 sachet (namely isomalt, hypromellose, and strawberry
flavour).
3. Excipients the placebo sachet (namely isomalt, hypromellose, strawberry
flavour, citric acid, 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, cognitive, 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 period from any of the
following prohibited medication prior to Visit 1 (Baseline 1) and remain without
prohibited medication through Visit 6.
1. N-Acetyl-DL-Leucine (e.g. Tanganil)
2. N-Acetyl-L-Leucine (prohibited if not provided as IMP in the IB1001-301 trial)
3. Sulfasalazine
4. Rosuvastatin.
- (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Scale for the Assessment and Rating of Ataxia (all jurisdictions except US);Modified Scale for the Assessment and Rating of Ataxia (US only) (ICTRP)
Spinocerebellar Ataxia Functional Index (SCAFI);Modified Disability Rating Scale;Physician's / Caregiver's / Patient's Clinical Global Impressions (CGI);EuroQuol- 5 Dimension (EQ-5D) Quality of Life Scale;Scale for the Assessment and Rating of Ataxia (US only) (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Michael Strupp, MD, mstrupp@intrabio.com, +44 8081 641283 (ICTRP)
Sekundäre IDs
IB1001-301 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT05163288 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar