Clinical Trials Register

Summary
EudraCT Number:	2009-013917-91
Sponsor's Protocol Code Number:	AIC246-01-II-02
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:	2009-12-01
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

Germany - BfArM

A.2

EudraCT number

2009-013917-91

A.3

Full title of the trial

A randomized, double-blind, placebo controlled trial to evaluate the safety, tolerability and antiviral activity of 12 weeks’ treatment with a new antiviral HCMV drug

A.4.1

Sponsor's protocol code number

AIC246-01-II-02

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	AiCuris GmbH & Co. KG
B.1.3.4	Country	Germany
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	AIC090027
D.3.2	Product code	AIC090027
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.1	CAS number	917389-23-3
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	60
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.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	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	AIC090027
D.3.2	Product code	AIC090027
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.1	CAS number	917389-23-3
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	120
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.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	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	AIC090027
D.3.2	Product code	AIC090027
D.3.4	Pharmaceutical form	Film-coated tablet
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.3.9.1	CAS number	917389-23-3
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	240
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	Film-coated 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	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated 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

Prevention of active human cytomegalovirus (HCMV) replication by re-infection or re-activation in HCMV seropositive patients after human blood precursor cell (HBPC) transplantation

MedDRA Classification

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 safety and efficacy of 3 different doses of AIC090027 with matching placebo. The incidence and time to onset of “HCMV prophylaxis failed” for the prevention of an active HCMV replication within an 84-day treatment period in HCMV seropositive allogeneic HBPC transplant recipients will be compared between each treatment group versus placebo.

E.2.2

Secondary objectives of the trial

To compare 3 different doses of AIC090027 versus matching placebo with regard to:
− the PK of AIC090027 at steady-state to establish an exposure effect relationship
− investigate the effect of AIC090027 on co-administered cyclosporine, tacrolimus, sirolimus, and everolimus
− the incidence and time to onset of HCMV End-Organ Disease alone.
− the incidence and time to onset of systemic detectable HCMV reactivation alone
− the incidence and time to onset of discontinuation of trial medication within the 84 day treatment period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients of any ethnic group aged ≥18 years on the day informed consent is given
2. Seropositive for HCMV IgG antibodies as tested by the local laboratory within 1 year before transplantation (if the patient had received HCMV IgG antibody treatment, the test must have been performed ≥30 days after HCMV IgG antibody administration). If repeated tests were performed 1 positive HCMV test confirms the patient as HCMV IgG seropositive.
3. First allogeneic HBPC transplantation performed within 40 days before randomization for one of the following diagnoses: leukaemia, lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, multiple myeloma, myelodysplastic and myeloproliferative disorder
4. Allogeneic human leukocyte antigen (HLA) A, B, C, DR identical related or unrelated donor bone marrow or peripheral blood progenitor cell transplant recipient using high resolution typing
5. Evidence of post transplantation engraftment (absolute neutrophil count remaining ≥500/mm3 for at least 3 consecutive sampling days documented by a minimum of 2 tests by the local laboratory)
6. An active HCMV replication not detectable by the HCMV standard evaluation of local laboratory (pp65 or HCMV-PCR) within 5 days before starting trial medication
7. Able to swallow tablets
8. Male patients who are surgically sterile (e.g. after vasectomy) or who must agree to use an adequate method of contraception during participation in the trial and for at least 2 complete months after the final trial visit and final examination. An adequate method of contraception is defined as sexual abstinence or single barrier method with their sexual partner.
Female patients who are surgically sterile (e.g. 2 sided tubal resection or ovariectomy) or post-menopausal (defined as older than 50 years of age or who have a history of no menses for at least 24 months)
or
Female patients of childbearing potential who must agree to use an adequate method of contraception during participation in the trial and for at least 1 complete month after the final trial visit and final examination. An adequate method of contraception is defined as sexual abstinence, single-barrier method, adequate hormonal contraception (to have started at least 7 days prior to Screening), or an intra-uterine device (IUD) (to have been in place for at least 2 months prior to Screening)
9. Negative beta-human chorionic gonadotropin (β-HCG) blood test for women
10. Written informed consent provided to participate in this trial.

E.4

Principal exclusion criteria

1. Previous allogeneic HBPC transplantation
2. Previous anti-HCMV therapy after this allogeneic HBPC transplantation
3. Ex-vivo T-cell depletion of the graft
4. Mismatched or cord blood transplant recipient
5. Any current uncontrolled active infection
6. Current or history of end-organ HCMV disease
7. Graft versus host disease (GVHD) of Grade 2 or higher (see Section 20.2) at day of randomization
8. Existing condition of requiring supplemental oxygen at day of randomization
9. Impaired liver function indicated by alanine aminotransferase (ALT) elevation ≥3 x upper limit of normal (ULN) (test performed by the local laboratory)
10. Reduced renal function indicated by a creatinine of ≥ 2 x ULN (test performed by the local laboratory)
11. Severe vomiting, diarrhea, or other gastrointestinal illness precluding the effective uptake of oral medication
12. Positive results in any of the virology tests for human immunodeficiency virus antibody (HIV-Ab), hepatitis C virus antibody (HCV-Ab) or hepatitis B surface antigen (HBsAg) (tests performed by the local laboratory)
13. Co-administration within 7 days before randomization of the CYP3A4 inducers: avasimibe, carbamazepine, phenytoin, rifampicin, and any preparations containing St. John’s wort (Hypericum perforatum)
14. Breastfeeding women
15. Current evidence for active abuse of alcohol or drugs
16. Known or suspected of not being able to comply with the trial protocol
17. Not able to communicate meaningfully with the Investigator and staff
18. Participation in investigational drug trials within the last 30 days before randomization for the trial

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the trial is the incidence and time to onset of “HCMV prophylaxis failed” within the 84 day treatment period as prevention of an active replication in HCMV positive patients. The definition for “HCMV prophylaxis failed” is:
• If the patient develops systemic detectable HCMV reactivation defined by:
- Two HCMV blood samples tested positive in the local laboratory, which were drawn at separate consecutive time-points (i.e. no negative samples at any intervening time-point) and which have led to the discontinuation of the trial medication and to the initiation of treatment with an alternative HCMV anti-viral medication.
- In addition, one HCMV blood sample from either of the 2 time-points that tested positive in the local laboratory must also have tested positive in the central laboratory.
Or
if the patient develops HCMV End-Organ Disease as defined by Ljungman et al. “Definitions of Cytomegalovirus Infection and Disease in Transplant Recipients” (Clinical Infectious Diseases 2002; 34: 1094-7)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

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

Yes

E.6.13.1

Other scope of the trial description

Genotypic analyses on HCMV DNA extracts for drug resistance testing

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

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

sequential dose groups: 60 mg per day, followed by 120 mg per day, followed by 240 mg per day

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

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

The end of trial is defined as the last trial-related visit of the last patient ongoing 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.1.3

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

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-12-01.

Yes

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

132

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)

Post-treatment care will be according to standard clinical practice and the Investigator’s judgment.

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

2009-12-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-02-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-10-17

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