Clinical Trials Register

Summary
EudraCT Number:	2010-024557-36
Sponsor's Protocol Code Number:	VHCRP1007
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-05-03
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

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2010-024557-36

A.3

Full title of the trial

A phase IV open-label multicentre, international trial of response guided treatment with directly observed pegylated interferon alfa 2b and self-administered ribavirin for patients with chronic HCV genotype 2 or 3 infection and ongoing injection drug use.

A.3.1

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

A trial of shortened Hepatitis C infection treatment in people who have an early response to treatment.

A.3.2

Name or abbreviated title of the trial where available

ACTIVATE

A.4.1

Sponsor's protocol code number

VHCRP1007

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01364090

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	The Kirby Institute
B.1.3.4	Country	Australia
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	The Kirby Institute
B.4.2	Country	Australia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ludwig-Maximilians-Universitat
B.5.2	Functional name of contact point	Markus Backmund
B.5.3	Address:
B.5.3.1	Street Address	Praxiszentrum Im Tal (PIT), Ludwig-Maximilians-Universitat, Addiction Medicine
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	Tal 9, Rgb.
B.5.3.4	Country	Germany
B.5.4	Telephone number	49894522856
B.5.5	Fax number	4989452285622
B.5.6	E-mail	Markus.Backmund@p-i-t.info

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	PegIntron
D.2.1.1.2	Name of the Marketing Authorisation holder	SP Europe
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	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-2B
D.3.9.1	CAS number	215647-85-1
D.3.9.3	Other descriptive name	PegIntron
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	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	0
D.3.9.3	Other descriptive name	POLYETHYLENE GLYCOL 400
D.3.10	Strength
D.3.10.1	Concentration unit	mm millimeter(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	immunomodifier
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	Rebetol
D.2.1.1.2	Name of the Marketing Authorisation holder	SP Europe
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	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	RIBAVIRIN
D.3.9.1	CAS number	36791-04-5
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	200
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	Yes
D.3.11.13.1	Other medicinal product type	direct acting antivirals, nuceosides and nucleotides (excluding reverse transcriptase inhibitors)

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Hepatitis C genotype 2 and 3 infection.

E.1.1.1

Medical condition in easily understood language

Hepatitis C is a viral infection of the blood which damages the liver.

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10008912
E.1.2	Term	Chronic hepatitis C
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate the proportion of patients with undetectable HCV RNA at 24 weeks post end of treatment (SVR24) following directly observed PEG-IFN alfa-2b (1.5 μg/kg weekly) in combination with self-administered ribavirin (800-1400 milligrams daily) for 12 weeks in participants with undetectable HCV RNA at week 4 of therapy, and for 24 weeks in participants with detectable HCV RNA at week 4 of therapy. In this feasibility study, the primary endpoint measurement of efficacy of treatment will be SVR24.

E.2.2

Secondary objectives of the trial

- to evaluate the percentage adherent to therapy (>80% of PEG-IFN, >80% of RBV, >80% of time)
- to evaluate safety and tolerability
- to evaluate the rate of recruitment
- to compare the percentage of patients with ETR and SVR12 among those who receive HCV therapy for 12 weeks (undetectable HCV RNA at week 4) and 24 weeks (detectable HCV RNA at week 4)
- to evaluate the change in illicit drug use during treatment
- to evaluate the change in opiate substitution therapy during treatment
- to evaluate the change in depression and suicidal ideation during treatment
- to evaluate the change in health related quality of life during treatment
- to evaluate the percentage of enrolled patients with a satisfactory completed CRF
- to allow the collection and storage of DNA and plasma samples with the aim of establishing a specimen bank for future immunovirological studies of HCV
- to study host genetic factors associated with HCV outcomes

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Participants 18 years of age or older.
2. Chronic HCV infection (HCV antibody and/or detectable HCV RNA in plasma ≥ 6 months, and HCV RNA positive at screening).
3. HCV genotype 2 or 3 infection.
4. Active injection drug use (defined as injection drug use within the 12 weeks prior to consent).
5. Compensated liver disease (Child-Pugh class A), where the following criteria must be met: a.INR< 1.8, b. No ascites (present or ever), c. No hepatic encephalopathy (present or ever) d. No bleeding varices (present or ever)
6. Patients with biopsy proven or suspected (Fibroscan > 10KPa or clinical signs) cirrhosis or transition to cirrhosis must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP <100 ng/mL within 2 months prior to screening.
7. Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug.
8. All fertile males and females must be using effective contraception (as defined in protocol section 7.3) during treatment and during the 24 weeks after treatment end.
9. Participants have voluntarily signed the informed consent form.

E.4

Principal exclusion criteria

1. Echocardiographic findings or a medical history suggesting current or previous endocardititis.
2. Active bacterial or mycobacterial infection.
3. Women with ongoing pregnancy or breast feeding.
4. Interferon or ribavirin therapy at any previous time.
5. Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) </=6 months prior to the first dose of study drug.
6. Any investigational drug </=6 weeks prior to the first dose of study drug.
7. HCV genotype 1, 4, 5, 6, or 7 infection.
8. HIV infection (positive test at screening for anti-HIV Ab)
9. Hepatitis B virus infection (positive test at screening for HBsAg)
10. Evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures).
11. History or other evidence of decompensated liver disease.
12. Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening.
13. Serum creatinine level >1.5 x upper limit of normal at screening.
14. Ongoing severe psychiatric disease, especially depression, as judged by the treating physician.
15. Frequent drug use that is judged by the treating physician to compromise treatment safety.
16. History of a severe seizure disorder or current anticonvulsant use.
17. History of immunologically mediated disease, severe chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
18. Thyroid dysfunction not adequately controlled (TSH and T4 levels out of normal range).
19. Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration) or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension.
20. Inability or unwillingness to provide informed consent or abide by the requirements of the study.
21. Male partners of women who are pregnant.
22. Hemoglobin <12 g/dL (<7.4 mmol/L) in women or <13 g/dL (<8.1 mmol/L) in men at screening.
23. Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic.
24. Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated.

E.5 End points

E.5.1

Primary end point(s)

EVR (early virological response) defined as undetectable HCV RNA at week 4 will be the determinant of treatment duration.
SVR24 (sustained virological response at 24 weeks) defined as the proportion of patients with undetectable HCV RNA at 24 weeks post end of treatment (week 36-shortened duration; week 48-standard duration).

E.5.1.1

Timepoint(s) of evaluation of this end point

EVR will be assessed after 4 weeks of treatment.
SVR24 assessment will be made 36 weeks after commencing treatment in the short duration arm, and 48 weeks after commencing treatment in the standard duration arm.

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Canada

Switzerland

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

End of trial is defined as the last visit of the last subject in the trial.

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

100

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)

Standard post treatment follow up.

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

2012-05-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-19

P. End of Trial
P.	End of Trial Status	Completed

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