Clinical Trials Register

Summary
EudraCT Number:	2018-003167-54
Sponsor's Protocol Code Number:	EIG-LNF-011
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:	2021-08-03
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-003167-54

A.3

Full title of the trial

A Phase 3, Matrix Design, Partially Double-Blind, Randomized Study of the Efficacy and Safety of 50 mg Lonafarnib/100 mg Ritonavir BID with and without 180 mcg PEG IFN-alfa-2a for 48 Weeks Compared with PEG IFN-alfa-2a Monotherapy and Placebo Treatment in Patients Chronically Infected with Hepatitis Delta Virus Being Maintained on Anti-HBV Nucleos(t)ide Therapy (D-LIVR)

Studio di fase 3, con disegno a matrice, parzialmente in doppio cieco, randomizzato sull’efficacia e la sicurezza di lonafarnib 50 mg / ritonavir 100 mg, due volte al giorno (BID), con e senza 180 mcg di PEG IFN-alfa-2a, per 48 settimane rispetto a PEG IFN-alfa-2a in monoterapia e trattamento con placebo in pazienti con infezione cronica da virus dell’epatite delta in terapia di mantenimento con nucleos(t)idi anti-HBV (D-LIVR)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A research study to evaluate the efficacy and safety of the study drug named Lonafarnib administrated with Ritonavir, in patients Chronically Infected with Hepatitis Delta Virus Being Maintained on Anti-HBV Nucleos(t)ide Therapy (D-LIVR)

Studio di ricerca volto a valutare l’efficacia e la sicurezza del farmaco di studio chiamato lonafarnib amministrato con ritonavir, in pazienti con infezione cronica da virus dell’epatite delta in terapia di mantenimento con nucleos(t)idi anti-HBV (D-LIVR)

A.3.2

Name or abbreviated title of the trial where available

D-LIVR

A.4.1

Sponsor's protocol code number

EIG-LNF-011

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03719313

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	EIGER BIOPHARMACEUTICALS, INC.
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	EIGER BIOPHARMACEUTICALS, INC.
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	Eiger BioPharmaceuticals, Inc.
B.5.2	Functional name of contact point	Colin Hislop
B.5.3	Address:
B.5.3.1	Street Address	2155 Park Blvd.
B.5.3.2	Town/ city	Palo Alto
B.5.3.3	Post code	CA 94306
B.5.3.4	Country	United States
B.5.4	Telephone number	+16504556406
B.5.5	Fax number	0000000
B.5.6	E-mail	chislop@eigerbio.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	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Entecavir Aurobindo
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated tablet
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	ENTECAVIR
D.3.9.1	CAS number	142217-69-4
D.3.9.2	Current sponsor code	NA
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tenofovir disoproxil
D.3.2	Product code	[NA]
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	tenofovir disoproxil
D.3.9.1	CAS number	147127-20-6
D.3.9.2	Current sponsor code	NA
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	245
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: 3
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	Yes
D.2.1.1.1	Trade name	NORVIR
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbvie Inc
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ritonavir
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Tablet
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	Ritonavir
D.3.9.1	CAS number	155213-67-5
D.3.9.2	Current sponsor code	Norvir
D.3.9.4	EV Substance Code	SUB10342MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
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: 4
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	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tenofovir alafenamide fumarate
D.3.2	Product code	[NA]
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	Tenofovir alafenamide fumarate
D.3.9.1	CAS number	1392275-56-7
D.3.9.2	Current sponsor code	NA
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	25
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: 5
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/3/13/1225
D.3 Description of the IMP
D.3.1	Product name	Lonafarnib
D.3.2	Product code	[MK-6336, SCH-66336, BP1515-YYC]
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	Lonafarnib
D.3.9.1	CAS number	193275-84-2
D.3.9.2	Current sponsor code	LNF, SARASAR, SCH 66336, EBP994
D.3.9.4	EV Substance Code	SUB21038
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	25
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: 6
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	Yes
D.2.1.1.1	Trade name	PEGASYS - 180 MCG SOLUZIONE INIETTABILE 4 FLACONCINI 1 ML USO SOTTOCUTANEO
D.2.1.1.2	Name of the Marketing Authorisation holder	ROCHE REGISTRATION LIMITED
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	pegylated interferon-alfa-2a Injection
D.3.2	Product code	[NA]
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.3.8	INN - Proposed INN	INTERFERONE ALFA-2A PEGILATO
D.3.9.1	CAS number	198153-51-4
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB16452MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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: 7
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	Yes
D.2.1.1.1	Trade name	PEGASYS
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	pegylated interferon-alfa-2a Injection
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Solution for infusion
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.3.8	INN - Proposed INN	PEGINTERFERON ALFA-2A
D.3.9.1	CAS number	198153-51-4
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB16452MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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: 8
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	Yes
D.2.1.1.1	Trade name	Norvir
D.2.1.1.2	Name of the Marketing Authorisation holder	AbbVie Deutschland GmbH & Co. KG
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ritonavir
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Tablet
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	RITONAVIR
D.3.9.1	CAS number	155213-67-5
D.3.9.2	Current sponsor code	Norvir
D.3.9.4	EV Substance Code	SUB10342MIG
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	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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

The proposed indication for lonafarnib coadministered with ritonavir is for the treatment of chronic HDV infection.
Approximately 5% of HBV-infected individuals are infected with HDV worldwide. Chronic HDV infection leads to more severe liver disease than HBV mono-infection, is associated with accelerated fibrosis progression, and has a higher risk of developing hepatocellular carcinoma. Currently no satisfactory therapy for HDV infection exist.

L'indicazione proposta per lonafarnib co-somministrato con ritonavir è per il trattamento dell'infezione cronica da HDV. Circa il 5% degli individui infetti da HBV sono infetti da HDV in tutto il mondo. L'infezione cronica da HDV porta a malattie del fegato più gravi rispetto alla monoinfezione da HBV, è associata a progressione della fibrosi accelerata e presenta un rischio più elevato di sviluppare carcinoma epatocellulare.Attualmente non c'è una terapia soddisfacente per l'infezione da HDV.

E.1.1.1

Medical condition in easily understood language

The proposed study is for the treatment of patients with chronic HDV infection.

Lo studio proposto è per il trattamento di pazienti con infezione cronica da HDV.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

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	10019763
E.1.2	Term	Hepatitis delta
E.1.2	System Organ Class	100000004862

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

The primary objectives are as follows:
• To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) (Week 48) in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.
• To compare the composite virologic and biochemical response rate at EOT (Week 48) in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.
Composite virologic and biochemical response is defined as a = 2 log10 reduction in HDV ribonucleic acid (RNA) level and alanine aminotransferase (ALT) normalization relative to baseline. Meeting either primary objective will lead to an efficacy conclusion.

Gli obiettivi principali sono i seguenti:
• Confrontare il tasso di risposta virologica e biochimica composita alla fine del trattamento (EOT) (Settimana 48) in pazienti che ricevono LNF 50 mg / RTV 100 mg BID vs pazienti che ricevono placebo.
• Confrontare il tasso di risposta virologica e biochimica composita all'EOT (Settimana 48) in pazienti che ricevono LNF 50 mg / RTV 100 mg BID con PEG IFN-alfa-2a 180 mcg QW vs pazienti che ricevono placebo.
La risposta virologica e biochimica composita è definita come una riduzione di <sub> 2 </ sub> log10 del livello di acido ribonucleico dell'HDV (RNA) e della normalizzazione dell'alanina aminotransferasi (ALT) rispetto al basale. Il raggiungimento dell'obiettivo primario porterà a una conclusione di efficacia.

E.2.2

Secondary objectives of the trial

The secondary objectives are as follows (see Protocol for details):
• Virologic Response
• Biochemical Response
• Histologic Response
• Lower Limit of Quantitation (LLOQ) Virologic Response
• Composite Virologic and Biochemical Response
• Individual Virologic and Biochemical Response
• Quality of Life
• Safety

Gli obiettivi secondari sono i seguenti (vedi Protocollo per i dettagli):
• Risposta virologica
• Risposta biochimica
• Risposta istologica
• Risposta virologica a limite inferiore di quantificazione (LLOQ)
• Risposta virologica e biochimica composita
• Risposta individuale virologica e biochimica
• Qualità della vita
• Sicurezza

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Chronic HDV infection for at least 6 months in duration, documented by a positive HDV antibody (Ab) test and HDV RNA >=500 IU/mL by quantitative polymerase chain reaction (qPCR) assay prior to initiation of study Treatment.
Non-genotype 1 HDV will be capped at 15% of total enrollment. Patients with a screening HDV RNA viral load < or = 4 log10 will make up between 35% and 45% of the total population.
2. Demonstrable suppression of HBV DNA (< 20 IU/mL) following a minimum 12 weeks of anti-HBV nucleos(t)ide treatment with entecavir or tenofovir (TDF or TAF) prior to initiating study therapy.
3. Serum ALT > 1.3 x upper limit of the normal range (ULN) and < 10 x ULN.
4. Willing and able to comply with study procedures and provide written informed consent.
5. Need to be able to read and understand language where the patient is participating in the study.
6. Able to self-administer medication orally and via subcutaneous (SC) injection.
7. Male and female participants who are 18 years of age or above.
8. Body mass index (BMI) of = 18 kg/m2 and weight = 45 kg.
9. Liver biopsy within 45 days of Day 1 demonstrating evidence of chronic hepatitis. If no liver biopsy is available, the patient must be willing to consent to and have no contraindication to liver biopsy.
10. ECGs demonstrating no acute ischemia or clinically significant (CS) abnormality and a corrected QT interval by Fridericia correction formula (QTcF) < 450 ms.
11. Normal dilated retinal examination.
12. Sexually active female patients of childbearing potential and sexually active male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study. Females of childbearing potential are all those except women who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.
For female patients:
• Progestin-based hormonal contraception (implant, injection, oral) associated with inhibition of ovulation for > or = 3 moths before screening. Use of a progestin-based implant or injection method requires the additional use of a barrier method (use of condom [male partner] or diaphragm with spermicide or cervical cap with spermicide) from screening. Use of a progestin-only, oral method requires the additional use of double barrier methods (use of condom [male partner] with either diaphragm with spermicide or cervical cap with spermicide) from screening or
• Intrauterine device (IUD) or intrauterine system (IUS) in place = 3 months before screening AND a barrier method (use of condom [male partner] or diaphragm with spermicide or cervical cap with spermicide) from screening, or
• Surgical sterilization of the partner (vasectomy = 1 month before screening) AND a barrier method (use of condom [male partner] or diaphragm with spermicide or cervical cap with spermicide) from screening, or
• Double-barrier methods (use of condom [male partner] with either diaphragm with spermicide or cervical cap with spermicide) from screening.
For male patients:
• Surgical sterilization (vasectomy = 1 month before screening) AND a barrier method (use of condom or diaphragm with spermicide or cervical cap with spermicide) from screening, or
• Consistently and correctly use a condom from screening AND female partner must agree to use a hormonal contraceptive, a nonhormonal nonbarrier method (eg, copper IUD), or a nonhormonal barrier method (eg, diaphragm with spermicide or cervical cap with spermicide).

1. Infezione cronica da HDV per almeno 6 mesi di durata, documentata da un test positivo dell'anticorpo HDV (Ab) e HDV RNA >=500 IU / mL mediante reazione a catena della polimerasi quantitativa (qPCR) prima dell'inizio del trattamento in studio.
L'HDV non-genotipo 1 sarà limitato al 15% del totale delle iscrizioni. I pazienti con una carica virale di HDV RNA di screening = 4 log10 costituiranno tra il 35% e il 45% della popolazione totale.
2. Soppressione dimostrabile del DNA dell'HBV (<20 UI / ml) a un minimo di 12 settimane di trattamento con nucleos (t) ide anti-HBV con entecavir o tenofovir (TDF o TAF) prima di iniziare la terapia di studio.
3. ALT sierico> 1,3 x limite superiore dell'intervallo normale (ULN) e <10 x ULN.
4. Disposti e in grado di rispettare le procedure di studio e fornire il consenso informato scritto.
5. È necessario essere in grado di leggere e capire la lingua in cui il paziente partecipa allo studio.
6. In grado di auto-somministrare farmaci per via orale e tramite iniezione sottocutanea (SC).
7. Partecipanti di sesso maschile e femminile che abbiano compiuto 18 anni o più.
8. Indice di massa corporea (BMI) = 18 kg / m2 e peso = 45 kg.
9. Biopsia epatica entro 45 giorni dal primo giorno che dimostra evidenza di epatite cronica. Se non è disponibile la biopsia epatica, il paziente deve essere disposto a consentire e non avere controindicazioni alla biopsia epatica.
10. ECG che non presentano ischemia acuta o anormalità clinicamente significativa (CS) e un intervallo QT corretto mediante formula di correzione di Fridericia (QTcF) <450 ms.
11. Esame retinico dilatato normale.
12. Le pazienti sessualmente attive in età fertile e i pazienti sessualmente attivi maschi con partner in età fertile devono concordare l'uso di metodi contraccettivi adeguati durante lo studio. Le donne in età fertile sono tutte quelle ad eccezione di donne che sono chirurgicamente sterili, con insufficienza ovarica documentata da un medico o che hanno almeno 1 anno di postmenopausa.
Per le pazienti di sesso femminile:
• Contraccezione ormonale a base di progestinico (impianto, iniezione, orale) associata a inibizione dell'ovulazione per un periodo > o = a 3 mesi prima dello screening. L'uso di un impianto o metodo di iniezione basato su Progestinico richiede l'uso aggiuntivo di un metodo di barriera (uso del preservativo [partner maschile] o del diaframma con spermicida o cappuccio cervicale con spermicida) dallo screening. Il solo uso di un metodo orale progestinico richiede l'uso aggiuntivo di metodi a doppia barriera (uso del preservativo [partner maschile] con diaframma con spermicida o con cappuccio cervicale con spermicida) dallo screening,
o
• Dispositivo intrauterino (IUD) o sistema intrauterino (IUS) in atto = 3 mesi prima dello screening E un metodo di barriera (uso del preservativo [partner maschile] o diaframma con spermicida o cappuccio cervicale con spermicida) dallo screening, o
• Sterilizzazione chirurgica del partner (vasectomia = 1 mese prima dello screening) E un metodo di barriera (uso del preservativo [partner maschile] o diaframma con spermicida o cappuccio cervicale con spermicida) dallo screening, o
• Metodi a doppia barriera (uso del preservativo [partner maschile] con diaframma con spermicida o tappo cervicale con spermicida) dallo screening.
Per i pazienti di sesso maschile:
• Sterilizzazione chirurgica (vasectomia = 1 mese prima dello screening) E un metodo di barriera (uso del preservativo o diaframma con spermicida o cappuccio cervicale con spermicida) dallo screening, o
• Utilizzare coerentemente e correttamente un preservativo dallo screening E la partner femminile deve accettare l'uso di un contraccettivo ormonale, un metodo non-ormonale non-barriera (ad es. Rame IUD) o un metodo di barriera non ormonale (ad es. Diaframma con spermicida o cappuccio cervicale con spermicida).

E.4

Principal exclusion criteria

1.Participation in a clinical trial with, or use of, any investigational agent within 30 days or 5 half-lives, whichever is longer, before screening
2.Previous use of LNF within 12 months before pre screening/screening
and all others exclusion criteris, as stated in the protocol

1. Partecipazione a uno studio clinico con o uso di qualsiasi agente investigativo entro 30 giorni o 5 emivite, a seconda di quale periodo sia più lungo, prima dello screening
2. Uso precedente di LNF entro 12 mesi prima del pre-screening / screening
e tutti gli altri criteri di esclusione, come riportato dal protocollo

E.5 End points

E.5.1

Primary end point(s)

• To compare the composite virologic and biochemical response rate at end-of-treatment (EOT) (Week 48) in patients who receive LNF 50 mg/RTV 100 mg BID vs patients who receive placebo.
• To compare the composite virologic and biochemical response rate at EOT (Week 48) in patients who receive LNF 50 mg/RTV 100 mg BID with PEG IFN-alfa-2a 180 mcg QW vs patients who receive placebo.
Composite virologic and biochemical response is defined as a = 2 log10 reduction in HDV ribonucleic acid (RNA) level and alanine aminotransferase (ALT) normalization relative to baseline. Meeting
either primary objective will lead to an efficacy conclusión.

• Per confrontare il tasso di risposta virologica e biochimica composita alla fine del trattamento (EOT) (Settimana 48) in pazienti che ricevono LNF 50 mg / RTV 100 mg BID vs pazienti che ricevono placebo.
• Confrontare il tasso di risposta virologica e biochimica composita all'EOT (Settimana 48) in pazienti che ricevono LNF 50 mg / RTV 100 mg BID con PEG IFN-alfa-2a 180 mcg QW vs pazienti che ricevono placebo.
La risposta virologica e biochimica composita è definita come una riduzione di = 2 log10 del livello di acido ribonucleico dell'HDV (RNA) e della normalizzazione dell'alanina aminotransferasi (ALT) rispetto al basale. Incontro
o l'obiettivo primario porterà ad una conclusione conclusiva.

E.5.1.1

Timepoint(s) of evaluation of this end point

-Week 48

48 settimane

E.5.2

Secondary end point(s)

• Virologic Response
• Biochemical Response
• Histologic Response
• Lower Limit of Quantitation (LLOQ) Virologic Response
• Composite Virologic and Biochemical Response
• Individual Virologic and Biochemical response
• Quality of Life
• Safety

• Risposta virologica
• Risposta biochimica
• Risposta istologica
• Risposta virologica a limite inferiore di quantificazione (LLOQ)
• Risposta virologica e biochimica composita
• Risposta individuale virologica e biochimica
• Qualità della vita
• Sicurezza

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 48 and week 24 post treatment

Settimana 48 2 settimana 24 dopo il trattamento

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

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

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Parzialmente in doppio ceco

Partially double blind

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

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

Canada

Israel

Moldova, Republic of

Mongolia

New Zealand

Pakistan

Taiwan

Turkey

United States

Belgium

Bulgaria

France

Germany

Italy

Romania

Spain

Sweden

Switzerland

United Kingdom

Greece

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 visit from last subject

Ultima visita dell'ultimo paziente

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

400

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients who demonstrate a meaningful reduction of HDV RNA by >= 2log10 or better but do not achieve durables levels (ie, < LLOQ [40 IU/ml]) for 24 weeks post treatment, may be offered a re treatment option in a rollover treatment protocol (EIG-LNF-012). Patients randomized into the placebo groups may also be enrolled. A long term follow up study is planned to assess durability of response and disease associated outcomes (EIG-LNF-014). Patients may EIG-LNF-011 and in EIG-LNF-012 may enroll.

Per pz con riduzione dell'RNA dell'HDV di> = 2 log10 o superiore che non raggiungono livelli durevoli (cioè <LLOQ [40 UI/ml]) per 24 sett dopo trattamento, può essere offerta opzione di retrattamento in protocollo rollover(EIG-LNF-012). Anche i pazienti randomizzati nei gruppi placebo possono essere arruolati. È previsto studio di follow-up a lungo termine per valutare la durata della risposta e gli esiti associati alla malattia (EIG-LNF-014). POssono essera arruolati i pazientiEIG-LNF-011/012

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-05

P. End of Trial
P.	End of Trial Status	Ongoing

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