Clinical Trials Register

Summary
EudraCT Number:	2015-002929-19
Sponsor's Protocol Code Number:	SCIENCE
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-06-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2015-002929-19

A.3

Full title of the trial

Stem Cell therapy in IschEmic Non-treatable Cardiac disease - SCIENCE

Stem Cell therapy in IschEmic Non-treatable Cardiac disease -SCIENCE

A.3.1

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

Stem cell therapy in heart failure

Stamcellebehandling ved hjertesvigt

A.3.2

Name or abbreviated title of the trial where available

SCIENCE

A.4.1

Sponsor's protocol code number

SCIENCE

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	Department of Cardiology, Rigshospitalet
B.1.3.4	Country	Denmark
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	Rigshospitalet
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Department of Cardiology, 2014, Rigshospitalet
B.5.2	Functional name of contact point	Jens Kastrup
B.5.3	Address:
B.5.3.1	Street Address	Blegdamsvej 9
B.5.3.2	Town/ city	Copenhagen OE
B.5.3.3	Post code	2100
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004535452819
B.5.5	Fax number	004535452705
B.5.6	E-mail	jens.kastrup@regionh.dk

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	Allogeneic adipose tissue-derived stromal cells
D.3.2	Product code	CSCC_ASC
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intracardiac use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CSCC_ASC
D.3.9.2	Current sponsor code	SCIENCE
D.3.9.3	Other descriptive name	Ex vivo cultured human mesenchymal stem cells
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	110
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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	Solution for injection
D.8.4	Route of administration of the placebo	Intracardiac use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ischemic heart disease and heart failure

Kranspulsåresygdom og hjertesvigt

E.1.1.1

Medical condition in easily understood language

Patients with heart failure have reduced cardiac pump function, physical
functional capacity and quality of life in spite of maximal tolerated
therapy and are candidates for stem cell therapy

Patienter med hjertesvigt der har nedsat hjertepumpefunktion, fysisk
aktivitetskapacitet og livskvalitet på trods af maksimal tolererede
behandling. Disse patienter er kandidater til stamcelleterapi

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10019279
E.1.2	Term	Heart failure
E.1.2	System Organ Class	100000004849

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 perform at clinical double-blind placebo-controlled CSCC_ASC
multicentre study in heart failure patients to investigate the
regenerative capacity of the CSCC_ASC treatment.

At udføre et klinisk dobbelt-blindet placebo-kontrolleret CSCC_ASC
multicenterstudie hos patienter med hjertesvigt for at undersøge den
regenerative kapacitet af CSCC_ASC behandling.

E.2.2

Secondary objectives of the trial

Improvement in cardiac function and clinical symptoms

Forbedringer i hjertets pumpefunktion og kliniske symptomer

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria:
1. 30 to 80 years of age
2. Signed informed consent
3. Chronic stable ischemic heart disease
4. Heart failure (NYHA II-III)
5. LVEF ≤45%
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) in sinus rhythm
7. Maximal tolerable heart failure medication
8. Medication unchanged two months prior to inclusion
9. No option for percutaneous coronary intervention (PCI) or coronary
artery bypass graft (CABG)
10. Patients who have had PCI or CABG within six months of inclusion
must have a new angiography less than one month before inclusion or at
least four months after the intervention to rule out early restenosis
11. Patients cannot be included until three months after implantation of
a cardiac resynchronisation therapy device

Inklusionskriterier:
1. 30 til 80 år
2. Underskrevet informeret samtykke
3. Kronisk stabil iskæmisk hjertesygdom
4. Hjerteinsufficiens (NYHA II-III)
5. LVEF ≤ 45%
6. Plasma NT-pro-BNP> 300 pg / ml (> 35 pmol / L) i sinusrytme
7. Maksimal tolereret hjertesvigtsmedicin
8. Medicin uændret to måneder forud for inklusion
9. Ingen mulighed for perkutan koronar intervention (PCI) eller koronar
bypassoperation (CABG)
10. Patienter, der har haft PCI eller CABG senest seks måneder efter
optagelsen skal have en ny angiografi mindre end en måned før
optagelse eller i mindst fire måneder efter interventionen for at
udelukke tidlig restenose
11. Patienter kan ikke deltage før tre måneder efter implantation af en
hjerte re-synkroniserings terapi apparat

E.4

Principal exclusion criteria

Exclusion criteria
1. Heart Failure (NYHA I or IV)
2. Acute coronary syndrome with elevation of CKMB or troponins,
stroke or transitory cerebral ischemia within six weeks of inclusion
3. Other revascularisation treatment within four months of treatment
4. If clinically indicated the patient should have a coronary angiography
before inclusion
5. Moderate to severe aortic stenosis (valve area < 1.3 cm2) or
valvular disease with option for surgery.
6. Diminished functional capacity for other reasons such as: obstructive
pulmonary disease (COPD) with forced expiratory volume (FEV) <1
L/min, moderate to severe claudication or morbid obesity
7. Clinical significant anaemia (haemoglobin < 6 mmol/L), leukopenia
(leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or
thrombocytopenia (thrombocytes < 50 109/L)
8. Anticoagulation treatment that cannot be paused during cell
injections
9. Patients with reduced immune response
10. History with malignant disease within five years of inclusion or
suspected malignity – except treated skin cancer other than melanoma
11. Pregnant women
12. Other experimental treatment within four weeks of baseline tests
13. Participation in another intervention trial

Eksklusionskriterier
1. hjerteinsufficiens (NYHA I eller IV)
2. Akut koronart syndrom med elevation af CKMB eller troponiner,
slagtilfælde eller forbigående cerebral iskæmi senest seks uger før
inklusion
3. Andre revaskularisering behandling inden for fire måneders periode
efter behandling
4. Hvis det er klinisk indiceret, bør patienten have en koronarangiografi
før inklusion
5. Moderat til svær aortastenose (klapåbning <1,3 cm2) eller valvulær
sygdom med mulighed for kirurgi.
6. Formindsket funktionsevne af andre årsager, såsom: obstruktiv
lungesygdom (KOL) med forceret ekspirations volumen (FEV) <1 L /
min, moderat til svær bensmerter eller fedme
7. Klinisk signifikant anæmi (hæmoglobin <6 mmol / L), leukopeni
(leukocytter <2 109 / L), leukocytose (leukocytter> 14 109 /L) eller
trombocytopeni (trombocytter <50 109 / L)
8. antikoagulationsbehandling som ikke kan pause under celleinjektioner
9. Patienter med nedsat immunforsvar
10. Historie med ondartet sygdom inden for fem år før inklusion
undtagen behandlet hudkræft bortset melanom
11. Gravide kvinder
12. Andre eksperimentelle behandlinger indenfor fire uger før baseline
tests
13. Deltagelse i et andet interventionsforsøg

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is change in left ventricle end-systolic volume
(LVESV) at 6 months follow-up between CSCC_ASC and placebo patients

Det primære endpoint er ændring i venstre ventrikel slut-systolisk
volumen (LVESV) ved 6 måneders opfølgning mellem CSCC_ASC og
placebo patienter.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months after treatment

6 måneder efter behandlingen

E.5.2

Secondary end point(s)

The secondary endpoints are safety evaluated by development of
allogeneic antibodies and laboratory safety measurements 1 and 6
months after treatment and changes in left ventricular ejection fraction
(LVEF), end-diastolic volume and myocardial mass at 6 months followup.
The changes in left ventricle function will be measured by echocardiography
(ECHO) or computed tomography (CT). Other secondary endpoints are changes in NYHA, CCS,
Kansas City Cardiomyopathy Questionnaire (KCCQ), 6 min walking test and NT-pro-
BNP. In addition, safety of allogeneic CSCC_ASCs with respect to
incidence and severity of serious adverse events and suspected
unrelated serious adverse events will be evaluated at 12 months followup.
A combined endpoint of
1. death, hospitalization for worsening heart failure including inserting
of a bi-ventricular pacemaker, hospitalization because of ventricular
tachycardia or fibrillation and increased heart failure medical treatment
1, 2 and 3 years after treatment
2. death, hospitalization for any cardiovascular reason, hospitalization
for worsening heart failure including inserting of a bi-ventricular
pacemaker, hospitalization because of ventricular tachycardia or
fibrillation and increased heart failure medical treatment 1, 2 and 3
years after treatment.

De sekundære endpoints er sikkerhed evalueret ved udvikling af
allogene antistoffer og laboratorium sikkerhedsmæssige målinger 1 og 6
måneder efter behandling og ændringer i venstre ventrikels
uddrivningsfraktion (LVEF), slutdiastolisk volumen og myokardiemasse
ved 6 måneders opfølgning. Ændringerne i venstre ventrikel funktion vil
blive målt ved ekkokardiografi (ECHO) eller computertomografi (CT).
Andre sekundære effektmål er ændringer i NYHA, CCS, Kansas City Kardiomyopati
Spørgeskema (KCCQ), 6 min gangtest og NT-pro-BNP. Desuden vil
sikkerheden for allogene CSCC_ASCs med hensyn til forekomsten og
sværhedsgraden af alvorlige bivirkninger og formodede uafhængige
alvorlige bivirkninger vurderes efter 12 måneders opfølgning.
En kombineret endepunkt
1. død, hospitalsindlæggelse for forværret hjertesvigt, herunder
indsættelse af et bi-ventrikulær pacemaker, hospitalsindlæggelse på
grund af ventrikulær takykardi eller hjerteflimmer og øget hjertesvigt
medicinsk behandling 1, 2 og 3 år efter behandling
2. død, hospitalsindlæggelse for enhver kardiovaskulær årsag,
hospitalsindlæggelse for forværret hjertesvigt, herunder indsættelse af
et bi-ventrikulær pacemaker, hospitalsindlæggelse på grund af
ventrikulær takykardi eller hjerteflimmer og øget hjertesvigt medicinsk
behandling 1, 2 og 3 år efter behandlingen.

E.5.2.1

Timepoint(s) of evaluation of this end point

1 and 6 months after treatment and 1, 2 and 3 years

1 og 6 måneder efter behandlingen, samt 1, 2 og 3 år

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)

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

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.8.2.4

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

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

The patients will have four follow-up visits the first year after treatment, then the
safety of the study will be follow year 2 and 3 after the therapy in hospital registries

Patienterne vil have fire klinisk follow-up besøg det første år efter behandlingen. Der vil
herefter være opfølgning år 2 og 3 af sikkerhedsdata via hospitalsregistre

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)

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

139

F.4.2

For a multinational trial

F.4.2.1

In the EEA

139

F.4.2.2

In the whole clinical trial

139

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)

The patients will be followed by the referring hospital or general practitioner.

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

2016-06-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-03-01

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials