ICH GCP - EU Clinical trials Registry - 2018-002880-25 (IT)

Summary
EudraCT Number:	2018-002880-25
Sponsor's Protocol Code Number:	LTE15174
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-29
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	GENZYME CORPORATION
B.1.3.4	Country	United States
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	Genzyme Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PPD Global
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	929 North Front Street
B.5.3.2	Town/ city	Wilmington
B.5.3.3	Post code	28401
B.5.3.4	Country	United States
B.5.4	Telephone number	+498957877131
B.5.5	Fax number	+498957877400
B.5.6	E-mail	Saban.Musoski@ppdi.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/3/14/1297; EU/3/14/1298
D.3 Description of the IMP
D.3.1	Product name	Fitusiran
D.3.2	Product code	[SAR439774]
D.3.4	Pharmaceutical form	Concentrate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1609016-97-8
D.3.9.2	Current sponsor code	SAR439774
D.3.9.4	EV Substance Code	SUB130859
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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
D.IMP: 2
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/3/14/1297; EU/3/14/1298 D.2.6 Has the IMP been
D.3 Description of the IMP
D.3.1	Product name	Fitusiran
D.3.2	Product code	SAR439774
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	1609016-97-8
D.3.9.2	Current sponsor code	SAR439774
D.3.9.4	EV Substance Code	SUB130859
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

Hemophilia A or Hemophilia B

Emofilia A o Emofilia B

E.1.1.1

Medical condition in easily understood language

Hemophilia is an inherited bleeding disorder in which the blood does not clot normally and can result in internal bleeding into the muscles and joints.

L'emofilia è una malattia emorragica ereditaria in cui il sangue non si coagula normalmente e può provocare emorragie interne nei muscoli e nelle articolazioni.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060613
E.1.2	Term	Hemophilia A (Factor VIII)
E.1.2	System Organ Class	100000004850

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10060614
E.1.2	Term	Hemophilia B (Factor IX)
E.1.2	System Organ Class	100000004850

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 characterize the long-term safety and tolerability of fitusiran

Caratterizzare sicurezza e tollerabilità a lungo termine di fitusiran

E.2.2

Secondary objectives of the trial

To characterize the long-term efficacy of fitusiran as assessed by the
frequency of:
- Bleeding episodes,
- Spontaneous bleeding episodes,
- Target joint bleeding episodes.
To characterize the effects of fitusiran on health-related quality of life
measures in participants =17 years of age.

Caratterizzare l'efficacia a lungo termine di fitusiran valutata in base alla frequenza di:
- episodi di sanguinamento,
- episodi di sanguinamento spontaneo,
- episodi di sanguinamento delle articolazioni target.
Caratterizzare gli effetti di fitusiran sulle misure della qualità di vita correlata allo stato di salute nei partecipanti di età = 17 anni.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age
01. Participant must be at least 12 years of age inclusive, at the time of signing the informed consent
Type of participant and disease characteristics
02. Participants with severe hemophilia A or B who have completed a Phase 3 fitusiran clinical trial
Sex
03. Male
A) There are no contraceptive requirements for this study except where required by local regulations.
Informed Consent
04. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. In countries where legal age of majority is above 18 years, a specific ICF must also be signed by the participant's legally authorized
representative.

I partecipanti sono eleggibili per l’inclusione nello studio solo se soddisfano tutti i criteri seguenti:
Età
01. Il partecipante deve avere un’età di almeno 12 anni compiuti al momento della firma del consenso informato

Tipo di partecipante e caratteristiche della malattia
02. Partecipanti con emofilia A o B grave che hanno completato una sperimentazione clinica con fitusiran di Fase 3

Sesso
03. Maschile
A) Non vi sono requisiti di contraccezione per questo studio, ad eccezione dei casi in cui previsto dalle normative locali.

Consenso informato
04. Essere in grado di fornire un consenso informato firmato che include il rispetto dei requisiti e delle limitazioni elencati nel modulo di consenso informato e in questo protocollo. Nei Paesi in cui la maggiore età legale è al di sopra dei 18 anni, deve essere firmato un ICF specifico anche dal rappresentante legale del partecipante.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria
apply:
Medical conditions
01. Completion of a surgical procedure within 14 days prior to screening,
or currently receiving additional factor concentrate or BPA infusion for
postoperative hemostasis
Prior/concomitant therapy
02. Current participation in ITI
03. Current use of factor concentrates or BPAs as regularly administered
prophylaxis designed to prevent spontaneous bleeding episodes
04. Use of compounds other than factor concentrates or BPAs for
hemophilia treatment
Prior/concurrent clinical study experience
05. Received an investigational drug or device, other than fitusiran,
within 30 days of anticipated IMP administration or 5 half-lives of the
IMP, whichever is longer
06. Current or prior participation in a gene therapy trial
Diagnostic assessments
07. ALT and/or AST >1.5× upper limit of normal reference range (ULN)
for patients who are naïve to fitusiran at study start; ALT and/or AST
>5× ULN for patients who were in the fitusiran arm in the parent study
Other exclusions
08. Individuals accommodated in an institution because of regulatory or
legal order; prisoners or participants who are legally institutionalized
09. Any country-related specific regulation that would prevent the
participant from entering the study
10. 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
11. Participants who are dependent on the Sponsor or Investigator (as
defined in section 1.61 of the International Council for Harmonisation
(ICH)-Good Clinical Practice (GCP) E6)
12. Participants are employees of the clinical study site or other
individuals directly involved in the conduct of the study, or immediate
family members of such individuals
13. Any specific situation during study implementation/course that may
rise ethics considerations
14. 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

I partecipanti sono esclusi dallo studio se soddisfano uno dei seguenti criteri:

Condizioni mediche
01. Completamento di procedura chirurgica entro i 14 giorni precedenti lo Screening o attuale trattamento con infusione aggiuntiva di concentrato di fattore o BPA per emostasi postoperatoria

Terapia precedente/concomitante
02. Attuale partecipazione a terapia di induzione della tolleranza immunologica (ITI)
03. Attuale uso di concentrati di fattore o BPA come profilassi regolarmente somministrata selezionata per prevenire episodi di sanguinamento spontaneo
04. Uso di composti diversi dai concentrati di fattore o BPA per il trattamento dell'emofilia

Esperienza precedente/concomitante in studi clinici
05. Trattamento con un farmaco o dispositivo sperimentale, diverso da fitusiran, nei 30 giorni precedenti la somministrazione prevista dell'IMP o entro 5 emivite dell'IMP, a seconda di quale sia il periodo più lungo
06. Partecipazione attuale o passata in una sperimentazione con terapia genica

Valutazioni diagnostiche
07. ALT e/o AST > 1,5 × il limite superiore della norma (ULN) per i pazienti naïve a fitusiran all'inizio dello studio; ALT e/o AST > 5 × ULN per i pazienti che erano nel braccio trattato con fitusiran nello studio originario.

Altre esclusioni
08. Soggetti che risiedono in un istituto a causa di un provvedimento normativo o legale; detenuti o partecipanti che sono istituzionalizzati per disposizione di legge
09. Qualsiasi normativa specifica del Paese che impedisca al partecipante di entrare nello studio
10. Partecipante non idoneo alla partecipazione, secondo il giudizio dello sperimentatore, qualunque sia la ragione, comprese condizioni mediche o cliniche, o partecipanti potenzialmente a rischio di non conformità alle procedure dello studio
11. Partecipanti che dipendono dallo Sponsor o dallo sperimentatore (come definito nella sezione 1.61 delle norme di buona pratica clinica (GCP), descritte dalle linee guida E6 della Conferenza Internazionale sull’Armonizzazione (ICH))
12. Partecipanti che sono dipendenti del centro dello studio clinico o qualsiasi altro soggetto direttamente coinvolto nella conduzione dello studio o familiari diretti di tali soggetti
13. Qualsiasi situazione specifica durante l'attuazione/lo svolgimento dello studio che possa sollevare considerazioni dal punto di vista etico
14. Sensibilità a uno qualsiasi degli interventi dello studio, o relativi componenti, o allergia a farmaci o altre allergie che, secondo il parere dello sperimentatore, costituiscano una controindicazione alla partecipazione allo studio

E.5 End points

E.5.1

Primary end point(s)

Incidence, severity, relatedness, and seriousness of AEs, and laboratory assessments

Incidenza, gravità, correlazione e serietà degli AE e valutazioni di laboratorio.

E.5.1.1

Timepoint(s) of evaluation of this end point

Through duration of the study (up to 55 months)

Per tutta la durata dello studio (fino a 55 mesi)

E.5.2

Secondary end point(s)

Annualized bleeding rate in the treatment period.
Annualized spontaneous bleeding rate in the treatment period.
Annualized joint bleeding rate in the treatment period.
Change in haemophilia quality of life questionnaire for adults physical
health score and total score in the treatment period (in participants =17
years of age).

Tasso annuale di sanguinamento nel periodo di trattamento.
Tasso annuale di sanguinamento spontaneo nel periodo di trattamento.
Tasso annuale di sanguinamento articolare nel periodo di trattamento.
Variazione nel questionario sulla qualità di vita specifico per l'emofilia a livello di punteggio di salute fisica dell'adulto e punteggio totale durante il periodo di trattamento (nei partecipanti = 17 anni di età).

E.5.2.1

Timepoint(s) of evaluation of this end point

Through duration of treatment (up to 48 months)

Per tutta la durata del trattamento (fino a 48 mesi)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Rescue therapy per standard of Care

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

Australia

Bulgaria

Canada

China

Denmark

France

Germany

Hungary

Iceland

India

Ireland

Italy

Japan

Korea, Democratic People's Republic of

Malaysia

Netherlands

Portugal

Russian Federation

South Africa

Spain

Taiwan

Turkey

Ukraine

United Kingdom

United States

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

Last Patient Last Visit (LPLV)

Ultima visita dell’ultimo paziente (LPLV)

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

Kliiniset tutkimukset Nct sivu

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot