ICH GCP - EU Clinical trials Registry - 2020-004400-34 (IT)

Summary
EudraCT Number:	2020-004400-34
Sponsor's Protocol Code Number:	LTS15823
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-08
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SANOFI-AVENTIS RECHERCHE E DEVELOPPEMENT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi S.r.l.
B.5.2	Functional name of contact point	Contact Point
B.5.3	Address:
B.5.3.1	Street Address	Viale L. Bodio 37/B
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20158
B.5.3.4	Country	Italy
B.5.4	Telephone number	800226343
B.5.5	Fax number	0239394168
B.5.6	E-mail	informazioni.medicoscientifiche@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/18/2122
D.3 Description of the IMP
D.3.1	Product name	Venglustat
D.3.2	Product code	[SAR402671, GZ402671 o GZ/SAR402671]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	venglustat malato
D.3.9.1	CAS number	1629063-78-0
D.3.9.2	Current sponsor code	GZ/SAR402671
D.3.9.3	Other descriptive name	GZ/SAR402671
D.3.9.4	EV Substance Code	SUB166602
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Congenital cystic kidney disease

Malattia policistica renale congenita

E.1.1.1

Medical condition in easily understood language

Congenital cystic kidney disease

Malattia policistica renale congenita

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10010428
E.1.2	Term	Congenital cystic kidney disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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

To determine the effect of early versus delayed treatment with venglustat on the total kidney volume (TKV) in participants at risk of rapidly progressive ADPKD.

Determinare l’effetto del trattamento precoce rispetto a quello ritardato con venglustat sul volume renale totale (total kidney volume, TKV) in partecipanti a rischio di ADPKD in rapida progressione

E.2.2

Secondary objectives of the trial

- To determine the effect of early versus delayed treatment with venglustat on the renal function (estimated glomerular filtration rate [eGFR]).
- To characterize the safety profile of venglustat.
- To evaluate the effect of venglustat on the lens by ophthalmological examination.
- To evaluate the effect of venglustat on mood using Beck Depression Inventory-II (BDI-II).

- Determinare l’effetto del trattamento precoce rispetto a quello ritardato con venglustat sulla funzionalità renale (velocità di filtrazione glomerulare stimata [estimated glomerular filtration rate, eGFR]).
- Caratterizzare il profilo di sicurezza di venglustat
- Valutare l’effetto di venglustat sul cristallino mediante un esame oftalmologico
- Valutare l’effetto di venglustat sull’umore, utilizzando la classificazione della depressione di Beck-II (Beck Depression Inventory-II, BDI-II).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female adult with ADPKD who has completed the treatment period in Stage 1 or Stage 2 of Study EFC15392.
- The patient has an eGFR >30 mL/min/1.73 m2:
a) measured at Visit 11 of the EFC15392 study for participant enrolled in the LTS15823 study at the time of Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.
b) measured at Screening visit for participant enrolled in the LTS15823 study not concomitantly to the Visit 12 (Month 24; end-of treatment visit) of the EFC15392 study.
- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
a) Male participants must agree to practice true abstinence in line with their preferred and usual lifestyle or to use double-contraceptive methods for the entire duration of the study and for at least 90 days following their last dose of IMP.
b) Female participants must have a negative urine pregnancy test at the Baseline visit and agree to practice true abstinence in line with their preferred and usual lifestyle or to use double contraceptive methods (including a highly effective method of contraception) for the entire duration of the study and for at least 6 weeks following their last dose of IMP.
- Capable of giving signed informed consent before performance of any study related procedures not part of standard medical care.
- Able to read, comprehend, and respond to the study questionnaires.

- Adulto di sesso maschile o femminile con ADPKD che ha completato il periodo di trattamento nella Fase 1 o nella Fase 2 dello studio EFC15392.
- Il/La paziente presenta un eGFR >30 ml/min/1,73 m2:
a) misurato alla Visita 11 dello studio EFC15392 per il/la partecipante arruolato/a nello studio LTS15823 al momento della Visita 12 (Mese 24; visita di fine trattamento) dello studio EFC15392.
b) misurato alla visita di screening per il/la partecipante arruolato/a nello studio LTS15823 non in concomitanza alla Visita 12 (Mese 24; visita di fine trattamento) dello studio EFC15392
- L'uso di contraccettivi da parte di uomini e donne deve essere in linea con le normative locali riguardanti i metodi di contraccezione per coloro che partecipano agli studi clinici.
a) I partecipanti di sesso maschile devono accettare di praticare una effettiva astinenza in linea con lo stile di vita preferito e abituale o di utilizzare metodi contraccettivi doppi per l’intera durata dello studio e per almeno 90 giorni dopo l’ultima dose dell’IMP.
b) Le partecipanti di sesso femminile devono presentare un test di gravidanza sulle urine negativo alla visita basale e accettare di praticare una effettiva astinenza se in linea con il proprio stile di vita preferito e abituale oppure di utilizzare metodi contraccettivi doppi (compreso un metodo contraccettivo altamente efficace) per l’intera durata dello studio e per almeno 6 settimane dopo l’ultima dose dell’IMP.
- In grado di fornire un consenso informato firmato prima dell’effettuazione di eventuali procedure correlate allo studio non incluse nelle cure mediche standard.
- In grado di leggere, comprendere e rispondere ai questionari dello studio.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
For participants who have lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study:
-The patient has a new clinically significant, uncontrolled medical condition that, in the opinion of the Investigator, would put the safety of the patient at risk through participation, or which would affect the efficacy or safety analysis if the condition exacerbated during the study, or that may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.
-A history of drug abuse and/or alcohol abuse or alcohol dependence during the lag phase between the end of the EFC15392 study and Screening visit (Visit 0) in the LTS15823 study when applicable.
-Administration of tolvaptan or other polycystic kidney disease-modifying agents (somatostatin analogues) within 3 months prior to the Screening visit (Visit 0) in the LTS15823 study when applicable.
-The patient is currently receiving potentially cataractogenic medications, including a chronic regimen (more frequently than every 2 weeks) of any route of corticosteroids (including medium and high potency topical steroids), or any medication that may cause cataract, according to the Prescribing Information.
-The patient has received strong or moderate inducers or inhibitors of CYP3A4 within 14 days or 5 half lives, whichever is longer, prior to the Baseline visit (including consumption of grapefruit-containing products within 72 hours of starting venglustat administration).
-Participation in another investigational interventional study or use of IMP, within 3 months or 5 half-lives, whichever is longer, before the Baseline visit (Visit 1) except participation in the EFC15392 study when applicable.
-Liver enzymes (alanine aminotransferase /aspartate aminotransferase) or total bilirubin >2 times the upper limit of normal unless the patient has the diagnosis of Gilbert syndrome. Patients with the Gilbert syndrome should have no additional symptoms or signs which suggest hepatobiliary disease and serum total bilirubin level no more than 3 mg/dL (51 µmol/L) with conjugated bilirubin less than 20% of the total bilirubin fraction.

For participants with or without lag phase between the end of EFC15392 study and entry into LTS15823 study:
-The patient is pregnant or lactating.
-Presence of severe depression as measured by Beck Depression Inventory II >28 at Visit 1 (for participants enrolled in the LTS15823 study at the time of the end of treatment visit of the EFC15392 study) or at Visit 0 (for participants enrolled in the LTS15823 study after the end-of-treatment visit of the EFC15392 study).
-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.

In presenza di uno dei seguenti criteri i partecipanti saranno esclusi dallo studio:
Per i/le partecipanti che presentano una fase di ritardo tra la fine dello studio EFC15392 e la visita di screening (Visita 0) nello studio LTS15823:
- Il/La paziente presenta una condizione medica clinicamente significativa e non controllata che, secondo il parere dello Sperimentatore, metterebbe a rischio la sicurezza del/la paziente con la partecipazione, o che influirebbe sull’analisi di efficacia o sicurezza se la condizione si aggravasse durante lo studio o che potrebbe interferire significativamente con l’aderenza allo studio, comprese tutte le valutazioni e le attività di follow-up prescritte.
- Anamnesi di abuso di droghe e/o abuso di alcol o dipendenza da alcol durante la fase di ritardo tra la fine dello studio EFC15392 e la visita di screening (Visita 0) nello studio LTS15823, ove applicabile.
- Somministrazione di tolvaptan o altri agenti modificanti la malattia policistica renale (analoghi della somatostatina) nei 3 mesi precedenti la visita di screening (Visita 0) nello studio LTS15823, ove applicabile.
- Il paziente sta attualmente ricevendo farmaci potenzialmente catarattogenici, compreso un regime cronico (con frequenza superiore a ogni 2 settimane) mediante qualsiasi via di somministrazione di corticosteroidi (inclusi gli steroidi topici a medio ed elevato potenziale) o di qualsiasi farmaco che possa provocare cataratte, in base alle Informazioni sulla prescrizione.
- Il/La paziente ha ricevuto induttori o inibitori, forti o moderati, di CYP3A4 nei 14 giorni o nelle 5 emivite precedenti la visita basale, a seconda di quale periodo duri di più (incluso anche il consumo di prodotti contenenti pompelmo entro 72 ore dall’inizio della somministrazione di venglustat.
- Partecipazione a un altro studio interventistico sperimentale o uso dell’IMP, entro 3 mesi o 5 emivite, a seconda di quale periodo duri di più, prima della visita basale (Visita 1), fatta eccezione per la partecipazione allo studio EFC15392, ove applicabile.
- Enzimi epatici (alanina aminotransferasi/aspartato aminotransferasi) o bilirubina totale >2 volte il limite superiore della norma (ULN) a meno che il/la paziente non presenti una diagnosi di sindrome di Gilbert. I/Le pazienti con la sindrome di Gilbert non devono presentare sintomi o segni aggiuntivi che suggeriscano malattia epatobiliare e il livello di bilirubina totale sierica non sia superiore a 3 mg/dl (51 µmol/l) con bilirubina coniugata inferiore al 20% della frazione di bilirubina totale.

Per i/le partecipanti con o senza fase di ritardo tra la fine dello studio EFC15392 e l’ingresso nello studio LTS15823:
- La paziente è in gravidanza o in allattamento.
- Presenza di depressione grave misurata mediante classificazione della depressione di Beck II (BDI-II) >28 alla Visita 1 (per i/le partecipanti arruolati/e nello studio LTS15823 al momento della visita di fine trattamento dello studio EFC15392) o alla Visita 0 (per i/le partecipanti arruolati/e nello studio LTS15823 dopo la visita di fine trattamento dello studio EFC15392).
- Sensibilità a uno qualsiasi dei trattamenti dello studio o a componenti dello stesso, o al farmaco o altre allergie che, secondo il parere dello sperimentatore, rappresentino una controindicazione alla partecipazione al presente studio

E.5 End points

E.5.1

Primary end point(s)

Percent change in TKV: Percent change in TKV based on magnetic resonance imaging (MRI) from the EFC15392 study baseline to 24 months of open-label extension study, in early treated and delayed-treated participants

Variazione percentuale del TKV: Variazione percentuale del TKV in base alla risonanza magnetica per immagini (RM) dal basale dello studio EFC15392 a 24 mesi di studio di estensione in aperto, in partecipanti trattati/e precocemente e in ritardo.

E.5.1.1

Timepoint(s) of evaluation of this end point

From the EFC15392 study baseline to 24 months of open-label extension study

Dal basale dello studio EFC15392 a 24 mesi di studio di estensione in aperto

E.5.2

Secondary end point(s)

1 - Change in eGFR: Change in eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) from the EFC15392 study baseline to 24 months of open label extension study, in early treated and delayed-treated participants
2 - Number of adverse events
3 - Change in lens clarity: Change from EFC15392 study baseline in the lens clarity by ophthalmological examination during the open label extension treatment-emergent period
4 - Change in score of Beck Depression Inventory- II (BDI-II): Change from EFC15392 study baseline in BDI II score during the open-label extension treatment emergent period

1- Variazione nell’eGFR: Variazione nell’eGFR (equazione della Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) dal basale dello studio EFC15392 a 24 mesi di studio di estensione in aperto, in partecipanti trattati/e precocemente e in ritardo
2- Numero di eventi avversi.
3- Variazione della trasparenza del cristallino: Variazione rispetto al basale dello studio EFC15392 della trasparenza del cristallino mediante esame oftalmologico durante il periodo di estensione in aperto emergente dal trattamento.
4- Variazione nel punteggio BDI-II: Variazione rispetto al basale dello studio EFC15392 nel punteggio BDI-II durante il periodo di estensione in aperto emergente dal trattamento

E.5.2.1

Timepoint(s) of evaluation of this end point

1: From the EFC15392 study baseline to 24 months of open-label extension study
2: From 1st treatment intake to last treatment of open-label extension study + 30 days
3,4: From EFC15392 study baseline to last treatment of open-label extension study + 30 days

1: dal basale dello studio EFC15392 a 24 mesi di studio di estensione in aperto
2: dalla prima somministrazione del trattamento all'ultimo trattamento dello studio di estensione in aperto + 30 giorni
3, 4: dal basale dello studio EFC15392 all'ultimo trattamneto dello studio di estensione in aperto + 30 giorni

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

Australia

Belgium

Canada

China

Czechia

Denmark

France

Germany

Israel

Italy

Korea, Republic of

Netherlands

Poland

Portugal

Romania

Spain

Taiwan

Turkey

United Kingdom

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

LVLS

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

Prove cliniche Nct

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici