E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Gaucher's disease type III |
3. típusú Gaucher-kór |
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E.1.1.1 | Medical condition in easily understood language |
Gaucher's disease type III |
3. típusú Gaucher-kór |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075699 |
E.1.2 | Term | Gaucher's disease type III |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the efficacy of venglustat compared to Cerezyme in adult and pediatric (12-18 years) GD3 patients by assessing: • Ataxia using the Scale for the Assessment and Rating of Ataxia (SARA) • Cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
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A venglusztát Cerezyme-mel szembeni hatásosságának értékelése felnőtt és gyermek (12 – 18 éves) GD3-betegeknél az alábbiak felmérésével: • Ataxia az Ataxia-mérési és értékelési skála (SARA) segítségével • Kogníció az 'ismételhető tesztsorozat a neuropszichológiai állapot felméréséhez (RBANS)' segítségével
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E.2.2 | Secondary objectives of the trial |
• Assess maintenance of spleen volume stability with venglustat compared to Cerezyme • Assess maintenance of liver volume stability with venglustat compared to Cerezyme • Assess maintenance of hemoglobin level stability with venglustat compared to Cerezyme • Assess maintenance of platelet count stability with venglustat compared to Cerezyme • Evaluate the safety and tolerability of venglustat compared to Cerezyme
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• A léptérfogat stabilitásának felmérése a venglusztáttal a Cerezyme-hez képest • A májtérfogat stabilitásának felmérése a venglusztáttal a Cerezyme-hez képest • A hemoglobinszint stabilitásának értékelése a venglusztáttal a Cerezyme-hez képest • A vérlemezkeszám stabilitásának értékelése a venglusztáttal a Cerezyme-hez képest • A venglusztát biztonságosságának és tolerálhatóságának értékelése a Cerezyme-hez képest
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The participant has received ERT (Cerezyme or other ERT; as deemed appropriate by local regulations) for at least 3 years prior to enrollment, on a stable dose for at least 6 months, is deemed clinically stable for at least 1 year by the Investigator and is within the therapeutic goals as all of the following: - Hemoglobin level of ≥11.0 g/dL for females and ≥12.0 g/dL for males - Platelet count ≥100 000/mm3 - Spleen volume <10 multiples of normal (MN) - Liver volume <1.5 MN - No bone crisis and free of symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathological fractures within 3 months prior to screening
- Adult participant is ≥18 years of age
- Pediatric participant is ≥12 years <18 years of age
- The participant has a clinical diagnosis of GD3 and a documented deficiency of acid beta-glucosidase activity confirming this diagnosis.
- The participant has a modified SARA score of 1 or above.
- The presence of gaze palsy, predominantly horizontal, with slow or absent saccades.
- If the participant has a history of seizures, they are well controlled under appropriate medication not identified as a strong or moderate inducer or inhibitor of CYP3A.
- Participants ≥ 30 kg of weight
- Contraception for sexually active male participants or female patient; not pregnant or breastfeeding; no sperm donating for male participant - Signed written informed assent/consent
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- A résztvevő legalább 3 évig a bevonás előtt kapott ERT-t (Cerezyme vagy más ERT; a helyi előírásoknak megfelelően), stabil adagban legalább 6 hónapon át, a vizsgálati orvos megítélése szerint legalább egy éve klinikailag stabil, és a résztvevő elérte az alábbi terápiás célok mindegyikét: - Hemoglobinszint ≥11,0 g/dl nőknél és ≥12,0 g/dl férfiaknál - Vérlemezkeszám ≥100 000/mm3 - Léptérfogat <10 normál érték többszöröse (MN) - Májtérfogat <1,5 MN - A szűrést megelőző 3 hónapon belül nem volt csontkrízis, tünetekkel járó csontbetegség, például osteonecrosisnak és/vagy kóros csonttöréseknek tulajdonítható csontfájdalom
- A felnőtt résztvevő ≥18 éves
- A gyermekkorú résztvevő ≥12 – <18 éves
- A résztvevőnek GD3 klinikai diagnózisa van, és a savas béta-glükozidáz aktivitás dokumentált hiánya megerősíti ezt a diagnózist.
- A résztvevő módosított SARA pontszáma 1 vagy magasabb.
- Látásbénulás, túlnyomórészt vízszintes, lassú vagy hiányzó szakkádokkal.
- Ha a résztvevő kórtörténetében rohamok vannak, azok jól kontrollálhatók megfelelő, nem erős vagy mérsékelt CYP3A-induktor- vagy -gátló gyógyszerrel.
- A résztvevők testsúlya ≥30 kg.
- Szexuálisan aktív férfiak és nők esetében a fogamzásgátló alkalmazása, női résztvevő nem terhes vagy nem szoptat, férfi résztvevő nem adományoz spermát.
- Aláírt betegtájékoztató/beleegyező nyilatkozat.
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - The participant is blood transfusion-dependent. - Prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase [ALT]/ aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal, unless the participant has a diagnosis of Gilbert Syndrome. - The participant has any clinically significant disease, other than GD, including cardiovascular (congenital cardiac defect, coronary artery disease, valve disease or left sided heart failure; clinically significant arrhythmias or conduction defect), hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (eg, hypokalemia, hypomagnesemia) or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the opinion of the Investigator. - The participant has renal insufficiency, as defined by an estimated glomerular filtration rate <30 mL/min/1.73m2 at the screening visit. - The participant has a history of cancer, except for basal cell carcinoma. - The participant has progressive myoclonic epilepsy. - The participant is pregnant (has a positive serum beta-human chronic gonadotropin [β-hCG]) or lactating. - The participant has a cortical cataract >one-quarter of the lens circumference (Grade cortical cataract-2) or a posterior subcapsular cataract >2 mm (Grade posterior subcapsular cataract-2). Participants with nuclear cataracts will not be excluded. - The participant requires use of invasive ventilatory support. - The participant requires use of noninvasive ventilator support while awake for longer than 12 hours daily. - The participant is scheduled for in-patient hospitalization including elective surgery, during the study. - The participant has had a major organ transplant (eg, bone marrow or liver). - A history of drug and/or alcohol abuse within the past year prior to the screening visit. - Chaperone therapy within 6 months, substrate reduction therapy other than venglustat within 6 months or venglustat substrate reduction therapy prior to enrollment. - The participant has received an investigational product, within 30 days prior to enrollment. - The participant is currently receiving potentially cataractogenic medications. - The participant has received strong or moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives from screening, whichever is longer, prior to screening. This also includes the consumption of grapefruit, grapefruit juice, or grapefruit containing products within 72 hours of starting venglustat. The participant is unwilling to abstain from consumption of grapefruit, grapefruit juice, or grapefruit containing products for the duration of the treatment period. - The participant, in the opinion of the investigator, is unable to adhere to the requirements of the study or unable to undergo study assessments (eg, contraindication for MRI). - Type of participant and disease characteristic: the participant has had a total splenectomy prior to enrollment. The patient had a partial splenectomy within 3 years prior to randomization. - Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures - Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in Scale for Assessment and Rating of Ataxia (SARA) modified total score - Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score |
- Az ataxia-mérési és értékelési skálán (Scale for Assessment and Rating of Ataxia, SARA) a módosított teljes pontszám közötti változás - Az ismételhető tesztsorozat a neuropszichológiai állapot felméréséhez (RBANS) teljes skálaindex-pontszámának változása
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Fom baseline to Week 52 |
Kiindulástól az 52. hétig |
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E.5.2 | Secondary end point(s) |
1/ Percent change in spleen volume
2/ Percent change in liver volume
3/ Change in hemoglobin level
4/ Percent change in platelet count
5/ Number of patients with treatment emergent adverse events (TEAEs)/ serious adverse events (SAEs)/ adverse events of special interest (AESIs)
6/ Change in score of Beck Depression Inventory II (BDI-II) during the treatment-emergent period
7/ Change in the lens clarity by ophthalmological examination during the treatment-emergent period
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1/ A léptérfogat százalékos változása
2/ A májtérfogat százalékos változása
3/ A hemoglobinszint változása
4/ A trombocitaszám százalékos változása
5/ A kezeléstől kialakuló nemkívánatos események/súlyos nemkívánatos események/különösen érdekes nemkívánatos események (TEAE-k/SAE-k/AESI-k), száma
6/ Változás a Beck depressziós kérdőív II (BDI-II) pontszámában a kezelés alatt
7/ A lencse tisztaságának változása szemészeti vizsgálattal a kezelés alatt
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From 1/ to 4/ and from 6/ to 7/: From baseline to Week 52
5/: From baseline to max of 3.5 years |
1/-től 4/ pontig, valamint 6/-tól 7/ pontig: kiindulástól az 52. hétig
5/: Kiindulástól max. 3.5 évig |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
China |
Egypt |
Japan |
Taiwan |
Turkey |
United States |
France |
Germany |
Hungary |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV |
Utolsó beteg utolsó vizit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 46 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 46 |