Clinical Trials Register

Summary
EudraCT Number:	2008-005560-13
Sponsor's Protocol Code Number:	Hep-Net-HIDIT-2
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-06-05
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2008-005560-13

A.3

Full title of the trial

A multicenter randomised study comparing the efficacy of pegylated interferon-alfa-2a plus placebo vs. pegylated interfeorn-alfa-2a plus tenofovir for the treatment of chronic delta hepatitis- The Hep-Net International Delta hepatits Interventional Trial II (HIDIT-II)

A.3.1

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

Treatment of delta hepatitis with pegylated interferon-alfa-2a and tenofovir or placebo

A.3.2

Name or abbreviated title of the trial where available

HIDIT-II

A.4.1

Sponsor's protocol code number

Hep-Net-HIDIT-2

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	Medizinische Hochschule Hannover
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Roche Pharma AG
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Gilead Sciences GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medizinische Hochschule Hannover
B.5.2	Functional name of contact point	Michael Manns
B.5.3	Address:
B.5.3.1	Street Address	Carl-Neuberg-Str. 1
B.5.3.2	Town/ city	Hannover
B.5.3.3	Post code	30625
B.5.3.4	Country	Germany
B.5.4	Telephone number	+495115323305
B.5.5	Fax number	+495115326820
B.5.6	E-mail	manns.michael@mh-hannover.de

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.2.1.1.1	Trade name	Viread
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Scienes International Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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.3.4	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	TENOFOVIR
D.3.9.1	CAS number	147127206
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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.2.1.1.1	Trade name	Pegasys
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 Kingdom
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	Peginterferon alfa-2a
D.3.2	Product code	Ro 25-8310
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.3.8	INN - Proposed INN	Peginterferon alfa-2a
D.3.9.1	CAS number	198153-51-4
D.3.9.2	Current sponsor code	Ro 25-8310
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

To compare the virological efficacy (HDV-RNA) and safety of 96 weeks of therapy with pegylated interferon-alfa-2a plus tenovofir to 96 weeks of therapy with pegylated interferon-alfa-2a plus placebo for the treatment with chronic delta hepatits virus.

E.1.1.1

Medical condition in easily understood language

Chronic delta hepatitis

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	15.1
E.1.2	Level	LLT
E.1.2	Classification code	10047455
E.1.2	Term	Viral hepatitis B without mention of hepatic coma, with hepatitis delta
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the virological efficacy (HDV-RNA) and safety of 96 weeks of therapy with PEG-IFN-2a plus tenofovir to 96 weeks of therapy with PEG-IFN-2a plus placebo for the treatment of patients with chronic delta hepatitis virus.

E.2.2

Secondary objectives of the trial

To explore the effects of the two treatment regimens on HDV-RNA-levels, HBsAg levels, HBV DNA, biochemical disease activity and liver histology. Virus-specific T cell responses during therapy and after 24 weeks of the treament will be analysed on stored PBMC samples if virological and biochemical efficacy has been shown. In addition, the objective of this study is to determine the virological and clinical long-term outcome of treatment of delta hepatitis.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age >= 18 years;
2. Positive HBsAg, for at least the prior 6 months, positive anti-HDV for at least 3 months and positive for HDV-RNA by PCR within the screening period.
3. Elevated serum ALT >= ULN but <= 10X ULN as determined by two abnormal values taken > 1 month apart during the 12 months before the first dose of study drug with at least one of the determinations obtained <=35 days prior to the first dose.
4. A liver biopsy obtained within the past 12 months demonstrating liver disease consistent with chronic hepatitis. Patients with cirrhosis (e.g. Metavir F4, Ishak fibrosis score = 5-6) on liver biopsy must also have a liver imaging investigation to rule out hepatic carcinoma.
5. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24 hour period prior to the first dose of test drug. Additionally, all fertile males with partners of childbearing age and females should use two reliable forms of effective contraception (combined) throughout the entire period of the study (treatment and for 4 months after treatment completion ): these may include, but are not limited to, birth control pills, IUDs, condoms, diaphragms, implants, surgical sterilization, or being in a post-menopausal state
6.Creatinine clearance > = 70 mL/min by the following formula:
((140-age in years) (body weight (kg)):((72) (serum creatinine [mg/dl]))
[Note: multiply estimated rate by 0.85 for women]
7. written informent consent

E.4

Principal exclusion criteria

1. Patients must not have received antiviral therapy for their chronic hepatitis D within the previous 6 months. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (<=7 day) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded.
2. Positive test at screening for HAV-Ag IgM, HCV-RNA or HCV-Ag or HIV-Ag.
3.Serum concentrations of ceruloplasmin or alfa1-antitrypsin consistent with an increased risk of metabolic liver disease.
4. Evidence of decompensated liver disease (Childs B-C).
5. History or other evidence of a medical condition associated with chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures, thalassemia).
6. Women with ongoing pregnancy or who are breast feeding.
7. WBC count of <3.000 cells/ mm3; neutrophil count <1.500 cells/mm3or platelet count <90.000 cells/mm3.
8. Evidence of alcohol and/or drug abuse within one year of entry.
9. Patients are excluded if any history of psychiatric disease, especially depression, or of suicidal attempts is evident.
10. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
11. History or other evidence of decompensated liver disease.
(Coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypo-albuminemia, ascites, and bleeding from oesophageal varices are conditions consistent with decompensated liver disease)
12. History or other evidence of chronic pulmonary disease associated with functional limitation.
13. History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
14. Evidence of an active or suspected cancer or a history of malignancy where there is a risk of cancer to reccur.
15.History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment (including systemic corticosteroids) <= 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
16. History of any organ transplantation with an existing functional graft
17. History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
18. History or evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration) or clinically relevant ophthalmological disorder (e.g. due to diabetes mellitus or hypertension)
19. Inability or unwillingness to provide informed consent or abide by the requirements of the study.
20. History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
21. Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.
22. Reassessments: If a patient fails to meet the above inclusion /exclusion criteria for a reason thought to be reversible, that patient may be reassessed for entry on two additional occasions at most. If the parameter out of range for inclusion was ALT > 10X ULN, the patient should be reassessed > 3 months after the date corresponding to the value that was > 10 X ULN. For other parameters, the reassessment may be done > 4 weeks following the original assessment.
23. History or evidence for any intolerance or hypersensitivity to pegylated interferon alpha-2a, tenofovir or other substances part of the study medication.
24. Current participation in any other investigational trial and participation in an other investigational trial within 3 months before the trial begins

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
• Negativation of HDV-RNA at the end of therapy

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 96

E.5.2

Secondary end point(s)

1. Negativation of HDV-RNA
2. Negativation of HDV-RNA
3. Normalization of ALT levels
4. HDV-RNA-levels
5. Quantitative HBsAg levels over time and loss of HBsAg and development of anti-HBs antibodies.
6. Suppression of HBV-DNA below 6 IU/ml using the Cobas TaqMan assay
7. Liver histology: Changes in Ishak scores for inflammation and fibrosis
8. Intrahepatic HBVcccDNA in patients with samples available
9. HBV- and HDV-virus-specific T cell responses
10. Quality of life (SF36 questionnaire)
11. Virological long-term outcome (HBsAg, HBeAg, anti-HBs, anti-HBe, HBV-DNA, HDV-RNA)
12. Clinical long-term outcome (normalization of ALT, development of hepatocellular carcinoma, hepatic decompensation, liver transplantation, death)

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Week 48 of treatment
2. 24 weeks after the end of treatment
3. End of therapy and at the end of follow-up
4. Over time of study
5. Over time of study
6. At treatment weeks 48 and 96 and 24 weeks after treatment
7. End of treatment as compared to pre-treatment biopsies at and after treatment
8. Only when available
9. During therapy and after 24 weeks of follow up if virological and biochemical efficacy has been shown, including measurements of serum cytokines and chemokines
10. Week 24, 48 and 96
11. 1, 2, 3, 4 and 5 years after the end of treatment
12. 1, 2, 3, 4 and 5 years after the end of treatment

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

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

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:

F.1.3

Elderly (>=65 years)

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

F.4.2.2

In the whole clinical trial

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)

After completion of the clinical study the patients will receive standard care

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

2009-06-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-05-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-08-02

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials