Clinical Trials Register

Summary
EudraCT Number:	2013-004934-14
Sponsor's Protocol Code Number:	EMASPK01
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-01-03
Trial 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

Czechia - SUKL

A.2

EudraCT number

2013-004934-14

A.3

Full title of the trial

EVEROLIMUS VERSUS MYCOPHENOLIC ACID IN SIMULTANEOUS PANCREAS
AND KIDNEY TRANSPLANTATION TO EVALUATE THE DIFFERENCES IN
RETINAL NEOVASCULARIZATION IN PATIENTS WITH DIABETIC
RETINOPATHY

EVEROLIMUS VERSUS MYKOFENOLOVÁ KYSELINA U PACIENTŮ PO
KOMBINOVANÉ TRANSPLANTACI LEDVINY A SLINIVKY BŘIŠNÍ ZA ÚČELEM
ZHODNOCENÍ VÝVOJE NOVOTVORBY CÉV NA SÍTNICI U PACIENTŮ S
DIABETICKOU RETINOPATIÍ

A.3.1

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

EVEROLIMUS VERSUS MYCOPHENOLIC ACID IN SIMULTANEOUS PANCREAS
AND KIDNEY TRANSPLANTATION TO EVALUATE THE DIFFERENCES IN
RETINAL NEOVASCULARIZATION IN PATIENTS WITH DIABETIC
RETINOPATHY

A.3.2

Name or abbreviated title of the trial where available

EMA-SPK

A.4.1

Sponsor's protocol code number

EMASPK01

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	Institut klinické a experimentální medicíny
B.1.3.4	Country	Czech Republic
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	Institut klinické a experimentální medicíny
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Institut klinické a experimentální medicíny
B.5.2	Functional name of contact point	IKEM
B.5.3	Address:
B.5.3.1	Street Address	Vídeňská 1958/9
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	14021
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420261364107
B.5.5	Fax number	+420261362820
B.5.6	E-mail	frantisek.saudek@ikem.cz

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	Certican
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis s.r.o., Praha, Česká republika
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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	Certican
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.3.11 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	Myfortic
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis, s.r.o., Praha, Česká Republika
D.2.1.2	Country which granted the Marketing Authorisation	Czech Republic
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	Myfortic
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.3.11 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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

simultaneous pancreas/kidney allograft transplantation

simultánní transplantace pankreatu a ledviny

E.1.1.1

Medical condition in easily understood language

simultaneous pancreas/kidney allograft transplantation

simultánní transplantace pankreatu a ledviny

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10048622
E.1.2	Term	Pancreatic transplant
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	LLT
E.1.2	Classification code	10023438
E.1.2	Term	Kidney transplant
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To compare the evolution of advanced diabetic retinopathy between
the 2 groups of Type 1-diabetic patients undergoing simultaneous
pancreas/kidney allograft transplantation in terms of the prevalence of
micro vascular retinal abnormalities (micro aneurysms, micro
hemorrhages and hemorrhages), range retinal neovascularization and
macular thickness at 1 and 2 years pot-transplant
2 a) To compare other parameters of diabetic retinopathy (visual
acuity, intraocular bleeding, need for laser therapy and other) between
the 2 groups
b) To compare graft survival, rejection rate, treatment tolerance and the
time to wound healing between the 2 groups

E.2.2

Secondary objectives of the trial

a) i. Change in visual acuity
ii. need for laser therapy
iii. new vessels formation within the field assessed by the color fundus
stereoscopic photographs
iv. new occurrence or change in cataract grading scale of more than 1 step
v. changes in retinal thickness compared to baseline examination assessed by OCT. Changes will be compared in the whole group and separately in subjects with pre-transplant OCT signs of macular (central macular thickness of > 250 μm or more)
vi. new occurrence of intravitreal bleeding registered by the patient and confirmed by the ophthalmologist
vii. retinopathy level assessed using the methodology of the EURODIAB IDDM Complications Study [1]
b) General parameters (patient and graft survival rates; rejection rate; treatment intolerance; the time to complete wound healing; blood glucose and C-peptide levels; creatinine clearance rate; glycosylated hemoglobin values)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Male or female patients, of 18 to 65 years of age, with a pre- or an
end-stage renal failure, Type 1-diabetic nephropathy, C¬-peptidenegative
(defined as C-peptide upper limit 0.2 nmol/l ,. If C-peptide is >
0.1 nmol/l, mixed-meal test will be performed with C-peptide upper limit
> 0.2 nmol/l).
2 Female patients of childbearing age must have a negative pregnancy
test and must agree to maintain effective birth control practice
throughout the study period (2 years).
3 Patient must have signed the Patient Informed Consent Form.
4 Patient must receive a primary simultaneous pancreas/kidney (SPK)
cadaver transplant, with either intestinal or bladder and either portal or
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systemic venous drainages.
5 Patients must have preserved sight at least on one eye with visual
acuity of at least 5/60 eye

E.4

Principal exclusion criteria

1. Patient is pregnant or breastfeeding.
2. Patient is allergic or intolerant to any drug comprising both
immunosuppressive protocols
3. Patient has a positive T-cell cross-match on the most recent serum
specimen.
4. Patient is known for active liver disease or has significant liver
disease; defined by ASAT and ALAT serum levels greater than 3 times the
upper limit of normal.
5. Patient has history of prothrombotic disorders.
6. Patient has malignancy or history of malignancy, with the exception of
adequately treated localized squamous cell or basal cell carcinoma,
without recurrence.
7. Patient has been included in another clinical trial protocol for any
investigational drug within 4 weeks prior to randomization.
8. Patient has any form of substance abuse, psychiatric disorder or
condition, which, in the opinion of the investigator, may invalidate
communication.
9. Patient receives a kidney transplant from a living donor, or receives
segmental pancreatic transplant, or a previous kidney transplant alone.
10. Pancreatic duct occlusion technique.
11. Donor is older than 65 years of age.
12. The use of any other commercial or investigational
immunosuppressive drugs is prohibited if it is not clinically indicated.
13. Patient has an immunological high risk, defined as a PRA grade >
50%

E.5 End points

E.5.1

Primary end point(s)

a) need for laser therapy except procedures that had been scheduled
already pre-transplant and were performed not later than 4 months
post-transplant
b) newly diagnosed proliferative retinopathy that was not present on
the pre-transplant examination
c) newly diagnosed clinically significant macular edema
d) worsening of visual acuity of more than 2 rows of Snellen´s
optotypes
e) occurrence of blindness

E.5.1.1

Timepoint(s) of evaluation of this end point

The study will last 2 years with a primary endpoint at 1 year and at the
study end. Extension of the study duration for survival data may be
decided by the Study board. Patients will be enrolled over a period of 3
years.

E.5.2

Secondary end point(s)

a) Ophthalmic parameters:
i. Change in visual acuity
ii. need for laser therapy except procedures that had been scheduled
already pre-transplant and were performed not later than 4 months
post-transplant
iii. new vessels formation within the field assessed by the color fundus
stereoscopic photographs (performed according to the EURODIAB IDDM
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Complications Study [1] ETDRS report number 10 [2]
iv. new occurrence or change in cataract grading scale of more than 1
step
v. changes in retinal thickness compared to baseline examination
assessed by OCT. Changes will be compared in the whole group and
separately in subjects with pre-transplant OCT signs of macular (central
macular thickness of > 250 μm or more)
vi. new occurrence of intravitreal bleeding registered by the patient and
confirmed by the ophthalmologist
vii. retinopathy level assessed using the methodology of the EURODIAB
IDDM Complications Study [1]
b) General parameters:
i. patient and graft survival rates
ii. rejection rate (kidney, pancreas or both). A kidney or pancreas
biopsy will be taken as clinically indicated in case of suspected rejection
of either kidney or pancreas. Biopsy analysis will be done according to
latest BANFF 97 criteria
iii. treatment intolerance (permanent mycophenolic acid or everolimus
withdrawal for more than 40 days
iv. the time to complete wound healing as assessed by the surgeon as
well as the transplant specialist and documented by photography
v. blood glucose and C-peptide levels (AUC) following a mixed meal test
vi. creatinine clearance rate calculated by the MDRD formula
vii. glycosylated hemoglobin values

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

LVLS

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

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

F.3.3.1

Women of childbearing potential not using contraception