Clinical Trials Register

Summary
EudraCT Number:	2010-024247-32
Sponsor's Protocol Code Number:	1263-203
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-14
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

France - ANSM

A.2

EudraCT number

2010-024247-32

A.3

Full title of the trial

A PHASE 2, RANDOMIZED, DOSE-RANGING STUDY TO ASSESS THE SAFETY AND ANTI-CYTOMEGALOVIRUS (CMV) ACTIVITY OF MARIBAVIR VERSUS VALGANCICLOVIR FOR TREATMENT OF CMV INFECTIONS IN TRANSPLANT RECIPIENTS WHO DO NOT HAVE CMV ORGAN DISEASE

A.3.1

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

A study to determine how safe and effective maribavir versus Valganciclovir is in treating cytomegalovirus(CMV) in transplant patients

A.4.1

Sponsor's protocol code number

1263-203

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	VIROPHARMA INCORPORATED
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	Viropharma Incorporated
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	Viropharma
B.5.2	Functional name of contact point	Clinical Study Manager
B.5.3	Address:
B.5.3.1	Street Address	Rue Montoyer 47
B.5.3.2	Town/ city	Brussels
B.5.3.3	Post code	B-1000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003223007811
B.5.5	Fax number	003227062421
B.5.6	E-mail	Katrien.Danneels@viropharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Maribavir
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	maribavir
D.3.9.1	CAS number	176161-24-3
D.3.9.2	Current sponsor code	VP 41263
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	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Valcyte
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products Limited
D.2.1.2	Country which granted the Marketing Authorisation	Romania
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	VALGANCICLOVIR
D.3.9.1	CAS number	175865-60-8
D.3.9.4	EV Substance Code	SUB00007MIG
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	450
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.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

CMV INFECTIONS IN TRANSPLANT RECIPIENTS

E.1.1.1

Medical condition in easily understood language

CMV INFECTIONS IN TRANSPLANT RECIPIENTS

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	10021819
E.1.2	Term	Infection in marrow transplant recipients
E.1.2	System Organ Class	10021881 - Infections and infestations

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	10021829
E.1.2	Term	Infection in solid organ transplant recipients
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

To assess the safety and tolerability of different doses of maribavir versus valganciclovir, administered orally for up to 12 weeks, for treatment of CMV infections in recipients of stem cell or solid organ transplants who do not have CMV organ disease.
To assess the antiviral activity of different doses of maribavir versus valganciclovir in this subject population.

E.2.2

Secondary objectives of the trial

To evaluate the pharmacokinetics and
pharmacodynamics of maribavir in this subject population.
To identify a maribavir dosing regimen for treatment of CMV infections in future studies.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be ≥18 years of age.
2. Be a recipient of stem cell or solid organ transplantation.
3. Have documented CMV infection in blood or plasma, with a screening value of ≥1,000 to ≤100,000 DNA copies/mL as determined by quantitative PCR or comparable quantitative CMV assay type. Results from either the central laboratory or a local laboratory can be used for qualification.
4. Have CMV infection that does not meet the definition of CMV organ disease at the time of enrollment (see Appendix IV).
5. Have a CMV infection that is not known to be resistant to ganciclovir/valganciclovir, foscarnet, or cidofovir based on genotypic evidence.
6. Have all of the following findings as part of screening laboratory assessment (results from either the central laboratory or a local laboratory can be used for qualification):
• Absolute neutrophil count (ANC ≥500/mm3 [0.5 x 109/L]
• Platelet count ≥25,000/mm3 [25 x 109/L]
• Hemoglobin ≥8 g/dL
7. If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test as part of screening laboratory assessments (pregnancy test results from either the central laboratory or a local laboratory can be used for qualification). Women of child bearing potential also must agree to use an acceptable method of birth control, as determined by the investigator, during the study drug administration period and for 3 months afterward. Hormonal contraceptives should not be used as the sole method of birth control.
If male, must agree to use an acceptable method of birth control, as determined by
the investigator, during the study drug administration period and for 3 months afterward.
8. Be able to swallow tablets.
9. Be informed of the nature of the study and provide written informed consent
before any study-specific procedures are performed. [NOTE: Subjects must be
fully able to give their consent.]

E.4

Principal exclusion criteria

Subjects must not:
1. Be receiving any of the following therapies when study drug is initiated:
• ganciclovir
• valganciclovir
• foscarnet
• cidofovir
• CMV immune globulin (CMV-IGIV, Cytogam®)
• leflunomide
• artesunate
NOTE: A subject may have received any of the above listed drugs prior to enrollment. If this is the case, these drugs must be discontinued, and a “washout” period of ≥24 hours is required between the last dose and commencement of dosing with study drug.
2. Have known allergies to one of the study medications (e.g., valganciclovir) or its excipients.
3. Have estimated creatinine clearance (CrCl) <10 mL/min or require dialysis when
study drug is initiated.
4. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the first dose of study drug that would preclude administration of oral/enteral medication.
5. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
6. Have any serious illness with expected survival less than 6 weeks.
7. Be pregnant (as determined by β-human chorionic gonadotropin testing prior to
initiation of study drug) or breastfeeding.
8. Have received any investigational (unapproved) agent with known anti-CMV
activity within 30 days before initiation of study drug.
9. Have any clinically significant medical or surgical condition that in the investigator’s or sponsor’s opinion could interfere with the administration of study drug or interpretation of study results, or compromise the safety or wellbeing of the subject.

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is to evaluate the safety and tolerability of different doses of maribavir versus valganciclovir in the study population. The primary analysis of safety will be the evaluation of treatment-emergent adverse events (TEAEs), defined as all AEs that
start during the study drug treatment period (and up to 7 days after the last dose of the study drug) and were not seen at baseline, or were seen at baseline but increased in frequency and/or severity during the study drug treatment period (and up to 7 days after the last dose of study drug).

E.5.1.1

Timepoint(s) of evaluation of this end point

7 days after the last dose of the study

E.5.2

Secondary end point(s)

Efficacy analyses will focus primarily on the antiviral effect of the study drug treatments on plasma CMV DNA concentrations within 3 and 6 weeks; corresponding endpoints will be
evaluated using modeling analyses.

E.5.2.1

Timepoint(s) of evaluation of this end point

3 weeks

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

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

LSLV

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:

144

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

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

160

F.4.2.2

In the whole clinical trial

160

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 of 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

2012-05-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-07-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-07-25

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