Clinical Trials Register

Summary
EudraCT Number:	2010-021113-23
Sponsor's Protocol Code Number:	TMC435HPC3007
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-24
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2010-021113-23

A.3

Full title of the trial

A Phase III, randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and tolerability of TMC435 vs. placebo as part of a treatment regimen including peginterferon alfa-2a and ribavirin in hepatitis C, genotype 1 infected subjects who relapsed after previous interferon-based therapy

A.3.2

Name or abbreviated title of the trial where available

Promise

A.4.1

Sponsor's protocol code number

TMC435HPC3007

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Tibotec Pharmaceuticals
B.1.3.4	Country	Ireland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TMC435
D.3.2	Product code	TMC435 (R494617 or JNJ-38733214-AAA, G007
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	not assigned yet
D.3.9.1	CAS number	92360-59-5
D.3.9.2	Current sponsor code	TMC435
D.3.9.3	Other descriptive name	R494617 or JNJ-38733214-AAA
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	150
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	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

Hepatitis C Virus (HCV)

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	15.0
E.1.2	Level	LLT
E.1.2	Classification code	10019752
E.1.2	Term	Hepatitis C virus (HCV)
E.1.2	System Organ Class	10022891 - Investigations

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 demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), with respect to the proportion of subjects with sustained virologic response (SVR) 24 weeks after the planned end of treatment (SVR24).

E.2.2

Secondary objectives of the trial

- Secondary Objectives: Reference is made to section 2 (Objectives) on page(s) 27 and 28 of the Clinical Trial Protocol
- Exploratory Objectives: Reference is made to section 2 (Objectives) on page(s) 27 and 28 of the Clinical Trial Protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female subject aged 18 years or above.
2. Subject must have a liver biopsy within 3 years prior to the screening visit (or between the screening and baseline visit) with histology consistent with chronic HCV infection:
a. If only inflammation is present, there should be laboratory evidence of chronic hepatitis C infection, i.e., presence of anti-HCV antibody or HCV RNA for at least 6 months prior to Day 1;
b. If cirrhosis (Metavir score F4) has been demonstrated on a previous liver biopsy,
the 3-year time window does not apply and there is no need for a new biopsy.
c. A biopsy is not required for subjects with bleeding disorders.
3. Subjects with bridging fibrosis (Metavir score F3) or cirrhosis (Metavir score F4) must have an ultrasound taken within 6 months prior to the screening visit (or between the screening and baseline visit) with no findings suspicious for hepatocellular carcinoma.
4. Genotype 1 HCV infection (confirmed at screening).
5. Plasma HCV RNA of > 10,000 IU/mL at screening.
Note: retesting of HCV RNA to assess eligibility will be allowed once, using an unscheduled visit during the screening period.
6. Subjects must have received (Peg)IFN-based therapy for at least 24 weeks with documented undetectable HCV RNA at the last measurement on treatment, and a subsequent detectable HCV RNA level within 1 year after the last medication intake.
7. Female subjects of childbearing potential or male subjects with a female partner of
childbearing potential must agree to use 2 forms of effective contraceptive methods (one of the methods needs to be a barrier method, e.g., condom or diaphragm) from at least 2 weeks prior to Day 1 (baseline) until at least 6 months after the last dose of PegIFN alfa-2a/RBV (or longer if dictated by local regulations), or not be heterosexually active, or vasectomized (male subjects) or have a vasectomized partner (female subjects), or be a female (subject or partner of male subject) of nonchildbearing potential (i.e., postmenopausal for at least 2 years or surgically sterile) (for further details, refer to Section 4.4, Prohibitions and Restrictions).
8. Subjects must be willing and able to comply with the protocol requirements.
9. Subjects must have voluntarily signed an ICF indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
Note: To participate in the optional pharmacogenomic component in this study (exploratory host genotyping), subjects must have voluntarily signed a separate ICF for this component. Refusal to give consent for this component does not exclude a subject from participation in the clinical study.

E.4

Principal exclusion criteria

1. Evidence of hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy)
2. Any liver disease of non-HCV etiology. This includes acute hepatitis A, drug- or alcoholrelated liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator.
3. Infection/co-infection with nongenotype 1 HCV.
4. Co-infection with HIV type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2
antibodies test at screening).
5. Co-infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive).
6. Previous discontinuation of (Peg-)IFN or RBV for an adverse event that in the opinion of the investigator would likely be treatment limiting during re-exposure to PegIFNalfa-2a or RBV.
7. Known allergy or hypersensitivity to TMC435, PegIFNalfa-2a, RBV, or any of the other
components of the formulation.
8. Medical conditions which are contraindications for PegIFNalfa-2a or RBV therapy:
a. Major uncontrolled depressive illness;
b. Organ transplant (other than cornea or hair transplant or skin graft);
c. Severe concurrent medical disease such as severe hypertension, significant coronary heart disease, poorly controlled diabetes, untreated thyroid disease, chronic obstructive pulmonary disease, severe infections (bacterial, viral, fungal, including acute tuberculosis), or hemoglobinopathies (thalassemia major or sickle-cell anemia);
d. Autoimmune hepatitis or other autoimmune conditions known to be exacerbated by PegIFN and RBV. Any other clinically significant disease that in the opinion of the investigator would be exacerbated by the known effects of PegIFN and RBV.
10. History of malignancy within 5 years of the screening visit (exceptions: squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence).
11. Subject with any of the following laboratory abnormalities:
a. Platelet count < 90,000/mm3;
b. Absolute neutrophil count < 1500 cells/mm3 (blacks: < 1200 cells/mm3);
c. Hemoglobin < 12 g/dL for women and < 13 g/dL for men;
d. Creatinine > 1.5 mg/dL;
e. ALT and/or AST > 10 x upper limit of laboratory normal range (ULN);
f. Total serum bilirubin > 1.5 x ULN;
g. Alpha-fetoprotein (AFP) > 50 ng/mL in subjects with cirrhosis (Metavir score F4).
Subjects without cirrhosis and AFP > 50 ng/mL must have an ultrasound between the
screening and baseline visit with no findings suspicious for hepatocellular carcinoma.
Note: retesting of abnormal laboratory values that lead to exclusion will be allowed once using an unscheduled visit during the screening period to assess eligibility.
12. Any other active clinically significant disease or clinically significant findings during
screening of medical history, physical examination, laboratory testing or ECG recording that, in the investigator?s opinion, would compromise the subject?s safety or could interfere with the subject participating in and completing the study.
Note: retesting of results that lead to exclusion will be allowed once using an unscheduled visit during the screening period to assess eligibility.
13. Current or past abuse of alcohol and/or recreational or narcotic drugs, which in the opinion of the investigator would compromise the subject?s safety and/or compliance with the study procedures.
14. Pregnant, planning on becoming pregnant, or breastfeeding female subject or male subject whose partner is pregnant or planning on becoming pregnant.
15. Subject who has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 30 days of screening.
16. Use of disallowed concomitant therapy.
17. Previous treatment with any HCV therapy other than IFN and RBV, including any directacting anti-HCV agents (e.g., NS5B polymerase, NS3/4A protease or NS5A inhibitor, or cyclophilin inhibitors).

E.5 End points

E.5.1

Primary end point(s)

See section 11.2.1 of the Protocol (pages 73 and 74)

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

tolerability

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

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.8.3

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

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

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	60
F.4.2	For a multinational trial
F.4.2.1	In the EEA	201
F.4.2.2	In the whole clinical trial	375

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

2011-03-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-02-04

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