Clinical Trials Register

Summary
EudraCT Number:	2015-002929-19
Sponsor's Protocol Code Number:	SCIENCE
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-04-25
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 - PEI

A.2

EudraCT number

2015-002929-19

A.3

Full title of the trial

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

Stammzelltherapie bei ischämischer, nicht behandelbarer Herzerkrankung - 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

Stammzelltherapie bei Herzinsuffizienz

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 mill in 5 ml
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

Ischämische Herzerkrankung und Herzinsuffizienz

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

Patienten mit Herzinsuffizienz haben trotz maximal verträglicher Therapie eine reduzierte kardiale Pumpfunktion, Leistungsfähigkeit und Lebensqualität und sind Kandidaten für Stammzelltherapie

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.

Durchführung einer doppelblinden, Placebo-kontrollierten CSCC-ASC multizentrischen Studie bei Patienten mit Herzinsuffizienz, um die regenerativen Eigenschaften der CSCC-ASC Therapie zu untersuchen

E.2.2

Secondary objectives of the trial

Improvement in cardiac function and clinical symptoms

Verbesserung der kardialen Funktion und der klinischen Symptome

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

1. Alter 30 – 80 Jahre
2. Schriftliche Einverständniserklärung
3. Stabile chronische ischämische Herzerkrankung
4. Herzinsuffizienz (NYHA II III)
5. lVEF < 45 %
6. Plasma NT-pro-BNP > 300 pg/ml (> 35 pmol/L) bei Sinusrhytmus
7. Maximal verträgliche Medikation
8. unveränderte Medikation mindestens 2 Monate vor Einschluss
9. Keine Option für Percutane Koronarintervention (PCI) oder Koronar-Bypass-Graft (CABG)
10. Patienten, bei denen innerhalb von 6 Monaten vor Einschluss eine PCI oder CABG durchgeführt wurde, müssen eine neue angiographische Untersuchung längsten eines Monats vor Einschluss oder mindestens 4 Monate nach PCI oder CABG erhalten, um eine frühe Restenose auszuschließen
11. Patienten, bei denen ein Gerät zur Kardiale Resynchronisierung implantiert wurde, können frühestens 3 Monate nach Implantation eingeschlossen werden.

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

1.Herzinsuffizienz (NYHA I oder IV)
2. Akutes Koronarsyndrom mit erhöhtem CKMB oder Troponin, Schlaganfall oder transitorische ischämische Zerebralischämie innerhalb von 6 Wochen vor Einschluss
3. Andere Revaskularisierungstherapie innerhalb von 4 Monaten vor Behandlungsbeginn
4. Wenn klinisch indiziert, sollte bei Patienten vor Einschluss eine Koronarangiographie durchgeführt werden
5. Moderate bis schwere Aortenstenose (Klappenbereich < 1,3 cm2) oder einer Herzklappenerkrankung mit chirurgischer Indikation
6. Aus anderen Gründen verminderte Leistungsfähigkeit, z.B. durch COPD mit einer provozierten FEV < 1 L/Min., moderate bis schwere Claudicatio oder morbide Adipositas.
7. Klinisch signifikante Anämie (Hämoglobin < 6 mmol/L), Leukopenie (Leukozyten < 2 109/L), Leukozytose (Leukozyten >14 109/L) oder Thrombozytopenie (Thrombozyten < 50 109/L)
8. Antikoagulationstherapie, die während der Zelltransplantation nicht unterbrochen werden kann.
9. Patienten mit reduzierter Immunreaktion
10. Patienten mit einer malignen Vorerkrankung innerhalb der letzten 5 Jahre vor Einschluss oder dem Verdacht auf eine maligne Erkrankung einschließlich Melanoma, mit Ausnahme von behandeltem Hautkrebs
11. Schwangere Frauen
12. Andere experimentelle Therapien weniger als 4 Wochen vor dem Baseline-Test
13. Teilnahme an einer anderen interventionellen Studie

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

Der primäre Endpunkt ist die Veränderung LVESV (left ventricle end-systolic volume) nach 6 Monaten zwischen CSCC-ASC-und Placebo-Behandlungsarm

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months after treatment

6 Monate nach Behandlung

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.

Die sekundären Endpunkte sind Sicherheit, evaluiert anhand der Entwicklung von allogenen Antikörpern und Laborparametern jeweils 1 und 6 Monate nach Behandlung sowie Veränderungen in der linksventrikulären Ejektionsfraktion, end-diastolisches Volumen und Myokardmasse nach 6 Monaten.
Die Veränderungen der linksventrikulären Funktion wird mittels echokardiographischer oder CT-Untersuchung gemessen.
Weitere sekundäre Endpunkte sind Veränderungen der NYHA-Klassifikation, CCS, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6-Minuten-Gehtest und NT-proBNP.
Zusätzlich wird die Sicherheit der allogenen Stammzellgabe CSCC_ASCs in Bezug auf Häufigkeit und Schweregrad von SAEs und SUSARs im 12 Monats-Follow-up bewertet.
Kombinierter Endpunkt nach 1,2, und 3 Jahren nach Stammzellgabe:
1. Tod, Hospitalisierung aufgrund verschlechterter Herzinsuffizienz einschließlich der Implantation eines bi-ventrikulären Herzschrittmachers, Hospitalisierung aufgrund von ventrikulärer Tachykardie oder Kammerflimmern und zusätzlicher Behandlung der zugrundliegenden Herzinsuffizienz.
2. Tod, Hospitalisierung aufgrund kardialer Erkrankung, verschlechterter Herzinsuffizienz einschließlich der Implantation eines bi-ventrikulären Herzschrittmachers, Hospitalisierung aufgrund von ventrikulärer Tachykardie oder Kammerflimmern und zusätzlicher Behandlung der zugrundliegenden Herzinsuffizienz.

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 und 6 Monate nach Behandlung und nach jeweils 1,2, und 3 Jahren

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

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

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

Patienten werden im ersten Jahr nach der Behandlung in 4 Follow-up Visiten untersucht, die Sicherheit der Stammzellgabe wird anschließend im Rahmen von Registern im Jahr 2 und 3 untersucht

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	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.1.2.1	Number of subjects for this age range:	60
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	79
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	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

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

2016-05-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-03-28

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

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