Clinical Trials Register

Summary
EudraCT Number:	2018-002653-29
Sponsor's Protocol Code Number:	NOMA
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-07-11
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

Spain - AEMPS

A.2

EudraCT number

2018-002653-29

A.3

Full title of the trial

Multicenter, randomized, dose-finding, parallel, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of intramuscular administration of allogeneic mesenchymal cells derived from adipose tissue in diabetic patients with critical ischemia of lower limbs without possibility of revascularization.

Ensayo clínico multicéntrico, aleatorizado, de búsqueda de dosis, de grupos paralelos, doble ciego y controlado con placebo, para evaluar la seguridad y eficacia de la administración intramuscular de células mesenquimales alogénicas derivadas de tejido adiposo en pacientes diabéticos con isquemia crítica de miembros inferiores sin posibilidad de revascularización.

A.3.1

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

Clinical trial to evaluate if the intramuscular administration in the legs of cells derived from the fatty tissue can improve the lack of blood flow in diabetic patients that are no candidates or in which other treatments to improve blood flow have already failed.

Ensayo clínico para evaluar si la administración intramuscular en las piernas de las células derivadas del tejido graso puede mejorar la falta de flujo sanguíneo en pacientes diabéticos que no son candidatos o en los que otros tratamientos para mejorar el flujo sanguíneo ya han fallado.

A.3.2

Name or abbreviated title of the trial where available

NOMA

A.4.1

Sponsor's protocol code number

NOMA

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	FUNDACION JIMENEZ DIAZ HEALTH RESEARCH INSTITUTE
B.1.3.4	Country	Spain
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	Fundación Jiménez Díaz
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FUNDACION JIMENEZ DIAZ HEALTH RESEARCH INSTITUTE
B.5.2	Functional name of contact point	CLINICAL RESEARCH UNIT
B.5.3	Address:
B.5.3.1	Street Address	Avenida Reyes Católicos 2
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28040
B.5.3.4	Country	Spain
B.5.4	Telephone number	00349155048003214
B.5.5	Fax number	0034915505353
B.5.6	E-mail	mireia.arcas@fjd.es

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	allogenic mesenchymal stem cell isolated from adipose tissue
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALLOGENEIC ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS EXPANDED
D.3.9.3	Other descriptive name	ALLOGENEIC ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS EXPANDED
D.3.9.4	EV Substance Code	SUB181445
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	10
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.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	allogenic mesenchymal stem cells derived from adipose tissue
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALLOGENEIC ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS EXPANDED
D.3.9.3	Other descriptive name	ALLOGENEIC ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS EXPANDED
D.3.9.4	EV Substance Code	SUB181445
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	10
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	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Critical ischemia of lower limbs in diabetic patients

isquemia crítica de miembros inferiores en pacientes diabéticos

E.1.1.1

Medical condition in easily understood language

lack of blood supply to the legs as a complication of diabetes

falta de riego sanguíneo en las piernas como complicación de la diabetes

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

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 evaluate the safety and tolerability of the administration of allogenic mesenchymal cells derived from adipose tissue in diabetic patients with critical ischemia of the lower limbs.

evaluar la seguridad y tolerabilidad de la administración de células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas en pacientes diabéticos con isquemia crítica de miembros inferiores

E.2.2

Secondary objectives of the trial

-To evaluate the preliminary efficacy of the treatment.
- To evaluate the quality of life after the administration of the treatment.

evaluar la eficacia preliminar del tratamiento, y los cambios en la calidad de vida de los pacientes

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients of both sexes.
 Age between 40 and 90 years.
 Type 2 diabetes established with more than 1 year since diagnosis.
 Severe grade vascular arteriosclerosis (category RB 4 and 5 mono or bilateral).
 Impossibility of surgical or endovascular revascularization or failure in revascularization surgery performed, at least 30 days before inclusion in the study, defining failure as direct non-arrival of vessels to the plantar arch.
 Normal biochemical parameters defined by:
o Leukocytes> 3000 / mm3
o Neutrophils> 1500 / mm3
o Platelets> 100,000 / mm3
o AST / ALT <2.5x upper limit of normal
 In patients with an ischemic ulcer, it must be stable for at least 1 week.
 Patients under conventional medical treatment for CLI.
 Women of childbearing age must obtain a negative result in a urine pregnancy test performed at the time of inclusion in the study and commit to using an effective contraceptive method during their participation in the study.
 Patients who have not participated in any other clinical trial during the 3 months prior to the inclusion visit.
 Patients who sign the informed consent.

E.4

Principal exclusion criteria

CLI with tissue loss in the target member (category 6 of RB).
 Previous major amputation in the target member.
 Uncontrolled hypertension (defined as PAS> 180 or PAD> 110 in at least 2 determinations during the selection period).
 Patients with severe heart failure or ejection fraction less than 30%.
 Patients with a previous diagnosis of ventricular arrhythmias or unstable angina.
 Patients with septicemia.
 Patients diagnosed with deep vein thrombosis in the 3 months prior to their inclusion in the study.
 Concomitant therapy that includes hyperbaric oxygen, angiogenic agents or Cox II inhibitors.
 Contraindication to RMN.
 Proliferative retinopathy without treatment.
 Diabetic nephropathy in hemodialysis.
 Patients previously treated with cell therapy, gene therapy or growth factors in the last year.
 Concomitant disease that limits life expectancy to 1 year or that does not ensure the follow-up period.
 Patients who have suffered a stroke or myocardial infarction in the 3 months prior to the inclusion visit.
 Severe anemia (hemoglobin <7.9g / dl) in the inclusion analysis.
 Patients with a previous diagnosis of chronic alcoholism.
 Any clinically significant anomaly detected in the Selection Period and which, in the opinion of the investigator, constitutes an impediment to the correct participation of the patient in the study or the fulfillment of the procedures established therein.

E.5 End points

E.5.1

Primary end point(s)

According to the primary objective of the study, the following variables are defined:
o Percentage and type of complications arising from treatment:
o Complications during anesthesia.
o Complications during cell implantation.
o Peri and postoperative complications.

E.5.1.1

Timepoint(s) of evaluation of this end point

At 12 months

E.5.2

Secondary end point(s)

 Evaluation of perfusion NMR vascularization.
 Score on the Rutherford-Becker Scale at 3, 6 and 12 months (0 to 6)
 Presence of ulcers: at 3, 6 and 12 months
 WIfI classification
Planimetry
 ITB measured at 3, 6 and 12 months.
 EVA scale measured at 3, 6, 12 months.
 Temperature at 3, 6 and 12 months.
 Perimetry at 3, 6 and 12 months.
 Neuropathic clinic measured at 3, 6 and 12 months.
 Amputations: yes / no.

Tertiary endpoints:
SF Score SF-12
VascuQol-6

E.5.2.1

Timepoint(s) of evaluation of this end point

All of them at baseline and 3, 6 and 12 months
Vasculogenesis through MRI only at 12 months

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

Yes

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

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

Last patient Last visit

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

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

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. Patients will be managed according to local standard of care after the end of the trial.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Spanish Clinical Research Network
G.4.3.4	Network Country	Spain

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-03-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-11

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

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