Clinical Trials Register

Summary
EudraCT Number:	2010-021821-10
Sponsor's Protocol Code Number:	MSC_Apceth_001
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-08-03
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

Germany - PEI

A.2

EudraCT number

2010-021821-10

A.3

Full title of the trial

Open, Randomized, Mono-centre, Two-Parallel Group Clinical Phase I/II Trial on the Evaluation of Tolerability and Efficacy of an Intravenous In-fusion of Human Bone-Marrow Derived Autologous, CD34-Negative Mesenchymal Stem Cell for the Treatment of Critical Limb Ischemia in Patients with Advanced Peripheral Arterial Occlusive Disease Subsequent to Percutaneous Transluminal Angioplasty

A.3.1

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

Clinical Phase I/II Trial on the Evaluation of Tolerability and Efficacy of an Intravenous Infusion of Human Mesenchymal Stem Cell for the Treatment of Critical Limb Ischemia

A.3.2

Name or abbreviated title of the trial where available

MSC-Apceth Phase I/II in POAD

A.4.1

Sponsor's protocol code number

MSC_Apceth_001

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	apceth 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	apceth GmbH & Co. KG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	apceth GmbH & Co. KG
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Max-Lebesche-Platz 30
B.5.3.2	Town/ city	München
B.5.3.3	Post code	81377
B.5.3.4	Country	Germany
B.5.4	Telephone number	+498970096080
B.5.5	Fax number	+49897009608130
B.5.6	E-mail	study001@apceth.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	MSC-Apceth
D.3.2	Product code	NA
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	human autologous CD34-negative, bone-marrow derived mesenchymal stem cells
D.3.9.3	Other descriptive name	human autologous CD34-negative, bone-marrow derived 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	5
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)	Yes
	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	Yes
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

Critical Limb Ischemia in Patients with Advanced Peripheral Arterial Occlusive Disease Subsequent to Percutaneous Transluminal Angioplasty

E.1.1.1

Medical condition in easily understood language

Critical Limb Ischemia in Patients with Advanced Peripheral Arterial Occlusive Disease Subsequent to Percutaneous Transluminal Angioplasty

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10066719
E.1.2	Term	Peripheral arterial occlusive disease aggravated
E.1.2	System Organ Class	100000004866

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. Evaluation of safety and tolerability of the treatment with MSC-Apceth for Infusion subsequent to PTA by collecting the safety parameters and adverse events in both treatment groups (PTA plus MSC-Apceth and PTA control group) during 12 months follow-up;

E.2.2

Secondary objectives of the trial

2. Comparison of the clinical course of therapy by the clinical parameters (PTA plus MSC-Apceth and PTA control group);

3. Comparison of the course of haemodynamic and vascular processes (PTA plus MSC-Apceth and PTA control group);

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult male or female patients between 40 to 80 years of age at the time of screening visit,
2. Patients with peripheral arterial occlusive disease (symptomatic PAOD), diagnosis of CLI defined as persistent, recurring ischemic rest pain for at least 2 weeks, and/or ulceration or gangrene of the foot or toe, with an ABPI ≤ 0.5,
3. Patients with staging of ≥III according to Fontaine and ≥4 according to Rutherford categories,
4. Patients fulfilling the criteria for an invasive re-vascularisation procedure (PTA) at the discretion of the investigator,
5. Patients without major amputation of the lower extremities within the period of 6 months after inclusion in the opinion of the investigator,
6. Inclusion is only possible for
• Patients of group A with bone marrow donation, who completed the questionnaire for bone marrow donation without abnormal findings;
• Patients with adequate organ and bone marrow function as defined by the following laboratory parameters:
Complete blood count/Reticulocytes Normal distribution
Haemoglobin ≥ 8 mmol/l
Leucocytes ≥ 3 x10E3/µL
Thrombocytes ≥ 100x10E3/µL
Quick ≥ 50%
PTT 25-40 s
Creatinine ≤ 2.0 mg/dL
Urea ≤ 100 mg/dL
gGT ≤ 2,5 upper normal value
GOT ≤ 2,5 upper normal value
GPT ≤ 2,5 upper normal value
Bilirubin ≤ 2.0 mg/dL
Alkaline phosphatase ≤ 2,5 upper normal value
CRP ≤ 5,0 mg/dL

• Patients with negative laboratory diagnostics for infections as summarised below:
Parameter Specification
HBs-Ag negative
Anti-HBs negative, positive*
Anti-HBc negative, positive*
HBV-NAT negative
Anti-HVC negative
HCV-NAT negative
Anti HIV 1/2 negative
HIV NAT negative
TPHA negative
Anti-CMV-ELISA CMV pos (IgG+/IgM-); CMV neg (IgG-/IgM-).
* if anti-HBc is positive, anti-HBs must be > 100 UI/l in adequate test and HBV-NAT negative

• Patients without irregular antibodies [blood group antibodies - non-ABO (iso-)antibodies most commonly of the IgG type] in the diagnostics of blood group with Rhesus-factor and antibody status;
• Patients with inconspicuous karyotyping results obtained for MSC-Apceth for Infusion final product.
7. Female patients of childbearing potential must have a negative urine pregnancy test recorded prior to the infusion of IMP, be non-lactating, and be willing to use adequate and highly effective method of contraception throughout the participation of the clinical trial, if sexually active. A highly effective method of birth control is defined as those which result in a low failure rate (i. e. less than 1% per year) when used consistently and correctly such as sterilization, implants, indictable, combines oral contracep-tives, some IUDs (hormonal), sexual abstinence or vasectomised partner.
8. Patients who are able to understand the requirements of the clinical trial, willing to provide voluntary written informed consent including data protection declaration and, additionally, the informed consent form according to the German Transplantation Law and the Law on Genome Diagnostics before any clinical trial related procedure is performed and agree to return for required follow-up visits

E.4

Principal exclusion criteria

1. Patients receiving systemic or direct target limb injection of antiangiogenic drugs,
2. Patients with concomitant wound treatments that include growth factors or tissue engineered products,
3. Patients with previous amputation of the talus, or above in the target limb,
4. Patients with wounds of a severity of greater than grade 2 on the Wagner Scale,
5. Patients with infection of the involved extremity(ies) manifest by fever, purulence and severe cellulites,
6. Patients with life-threatening ventricular arrhythmia,
7. Patients with unstable angina pectoris,
8. Patients with ST – segment elevation myocardial infarction and/or TIA/CVA within 6 months prior to enrolment,
9. Patients with severe congestive heart failure (i.e. NYHA Stage IV),
10. Patients with uncontrolled hypertension (defined as diastolic blood pressure >110 mmHg or systolic blood pressure >180 mmHg during screening),
11. Patients requiring uninterruptible anticoagulation that cannot be stopped for 24 hours prior to investigational treatment,
12. Patients with the diagnosis of end stage renal disease requiring dialysis (grade 5),
13. Patients with an uncontrolled diabetes mellitus (HbA1c > 9%),
14. Patients with any clinical sign of severe pulmonary disease and/or infection, uncontrolled lung disease including lung fibrosis, as defined by respiratory insufficiency or chest X-ray,
15. Patients with active hepatitis B-, or C- infection, or a positive test for HIV, or treponema pallidum (syphilis) at screening (refer to paragraph 6 in inclusion criteria),
16. Patients having any history of malignant tumour in the anamnesis or are currently on tumour treatment,
17. Patients with a documented history of active autoimmune disorders requiring systemic immunosuppressive therapy or an immunotherapy within 4 weeks prior to clinical trial enrolment (visit 1),
18. Patients with known allergies to protein products (e.g. porcine trypsin used in the cell production process) and X-ray contrast medication,
19. Patients with a history of severe alcohol or drug abuse within 3 months before screening in visit 1.
20. Patients who are pregnant or breast-feeding women or women of childbearing potential not protected by a highly effective contraceptive method of birth control,
21. Patients who are unsuitable for a MSC stem cell therapy in the opinion of the investigator,
22. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s),
23. Patients unwilling or unable to comply with the clinical trial procedures,
24. Patients who are unwilling to consent to storage and saving and transmission of pseudonymous medical data for clinical trial reasons,
25. Patients who are legally incapacitated,
26. Patients who are legally detained in an official institute.

E.5 End points

E.5.1

Primary end point(s)

1. Evaluation safety and tolerability of the treatment with MSC-Apceth for Infusion subsequent to PTA by collecting the safety parameters described below and adverse events in both treatment groups during 12 months follow-up;
2. Comparison of the clinical course of therapy by clinical parameters;
3. Comparison of the course of haemodynamic and vascular processes

E.5.1.1

Timepoint(s) of evaluation of this end point

over the course of the clinical trial

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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)

Yes

E.7.1.1

First administration to humans

Yes

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Percutaneous transluminal Angioplasty alone

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

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

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

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:

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

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.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)

NONE

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

2011-01-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-28

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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