Clinical Trials Register

Summary
EudraCT Number:	2014-000307-26
Sponsor's Protocol Code Number:	CeTMAd-VIH-2014
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-02-24
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

Spain - AEMPS

A.2

EudraCT number

2014-000307-26

A.3

Full title of the trial

Clinical trial Phase I/II, test of concept, double blind, randomized, controlled with placebo, to evalue the safety and efficiency of the treatment with expanded adult mesenchymal stem cells from allogenic adipose tissue, in patients with HIV infection with controlled viral load and immunological discordant response.

Ensayo clínico Fase I/II, de prueba de concepto, doble ciego, aleatorizado, controlado con placebo, para valorar la seguridad y eficacia del tratamiento con células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas, en pacientes con infección por el VIH con viremia controlada y respuesta inmunológica discordante.

A.3.1

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

Study with stem cells from allogenic adipose tissue, in patients with HIV infetion.

Estudio en pacientes con VIH con viremia controlada y respuesta inmunológica discordante, con células procedentes de tejido adiposo de un donante

A.4.1

Sponsor's protocol code number

CeTMAd-VIH-2014

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	Iniciativa Andaluza en Terapias Avanzadas-Fundación Pública Andaluza Progreso y Salud
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	Regional Ministry of Health
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	Iniciativa Andaluza en Terapias Avanzadas-Fundación Pública Andaluza Progreso y Salud
B.5.2	Functional name of contact point	Ana Cardesa Gil
B.5.3	Address:
B.5.3.1	Street Address	C/ Algodón s/n (Esquina Avda Hytasa)
B.5.3.2	Town/ city	Sevilla
B.5.3.3	Post code	41006
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34NA955048366NA
B.5.5	Fax number	+34NA955267002NA
B.5.6	E-mail	ana.cardesa@juntadeandalucia.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	Células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas
D.3.2	Product code	CeTMAd
D.3.4	Pharmaceutical form	Solution for infusion
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	Células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas
D.3.9.2	Current sponsor code	CeTMAd
D.3.9.3	Other descriptive name	Células mesenquimales troncales adultas alogénicas de tejido adiposo expandidas
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000000
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 infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Infection for HIV with controlled viral load and immunological discordant response

Infección por el VIH con viremia controlada y respuesta inmunológica discordante.

E.1.1.1

Medical condition in easily understood language

Infection for HIV

Infección por VIH

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10001509
E.1.2	Term	AIDS
E.1.2	System Organ Class	100000004862

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 evaluate the safety of the intravenous infusion of 4 doses of allogenic mesenchimal stem cells from adipose tissue (ASC), in patients with infection for HIV and immunological discordant response.

2. To evaluate the efficiency of the intravenous infusion of 4 ASC's doses in the immunological recovery after 3 monthly cycles of CeTMAd's infusion and 1 additional infusion in week 20 in patients with infection for HIV and immunological discordant response.

1. Evaluar la seguridad de la infusión intravenosa de 4 dosis de células mesenquimales troncales alogénicas de tejido adiposo (CeTMAd), en pacientes con infección por VIH y respuesta inmunológica discordante.
2. Evaluar la eficacia de la infusión intravenosa de 4 dosis de CeTMAd en la recuperación inmunológica tras 3 ciclos mensuales de infusión de CeTMAd y una infusión adicional en semana 20 a pacientes con infección por VIH y respuesta inmunológica discordante.

E.2.2

Secondary objectives of the trial

To analyze the evolution of the following parameters throughout 1 year after 4 ASC's infusions (1 x 3 monthly infusion plus an additional infusion in week 20)

1. Cellular and soluble markers of AII.
2. Changes on proviral load in PBMCs.
3. To evaluate the relation between the changes in the cell counts of lymphocytes T CD4 + and his % percentages with those observed in the AII markers.

Analizar la evolución de los siguientes parámetros a lo largo de un año tras 4 infusiones de CeTMAd (1 x 3 con una periodicidad mensual más otra adicional en semana 20)
1. Cambios en la AIp, mediante marcadores celulares y solubles.
2. Cambios en ADN proviral integrado en PBMCs y/ en CD4+.
3. Evaluar la relación entre los cambios en los recuentos de linfocitos T CD4+ y sus % porcentajes con los observados en la AIp.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. HIV- 1 infection
2. Both sex > 18 years old
3. In antirretrovial treatment
4. HIV viral load < 50 copies/ml during > 1 year
5. CD4+ value < 350/?l
6. Immunological discordant response (IDR) defined as:
- increase <75 or <150 CD4 + / µl after one or two years of undetectable viral load, respectively with the basal situation
, or
- recount of CD4 + <350/?l after 3 years of anti-retroviral treatment and undetectable viral load (<50 copias/ml) ? 1 year.
7. Writen inform consent form from the patients.
8. Commitment to use a contraceptive method with proved efficiency in men and women during the duration of the clinical trial

1. Infección por VIH-1
2. Edad ? 18 años. Ambos sexos
3. En tratamiento antirretroviral
4. Carga viral VIH < 50 copias/ml durante ? 1 año
5. Valor de CD4+ <350/?l.
6. Respuesta Inmunológica discordante (RID) definida como:
? incremento <75 o <150 CD4+/µl tras uno o dos años de viremia indetectable, respectivamente, con respecto a la determinación basal
o bien,
? recuento de CD4+ <350/?l tras 3 años de tratamiento antirretroviral y viremia indetectable (<50 copias/ml) ? 1 año.
7. Consentimiento informado por escrito del paciente
8. Compromiso de utilización de un método anticonceptivo de eficacia probada tanto en hombres como en mujeres durante la duración del ensayo clínico.

E.4

Principal exclusion criteria

1. Pregnancy, lactation, or refusal to use contraceptive methods with proved efficiency in men and women.
2. Opportunists infections in treatment
3. Active coinfecctions for virus B and C of the hepatitis
4. Stages C of liver cirrosis, according to Child Plugh classification.
5. Portal hypertension and / or hypersplemism of any etiology
6. Presense of malignant neoplasm.
7. Treatment in the last twelve months with steroids, inmunomodulators, interferon, chemotherapy or any treatment that could reverberate in the number of CD4.
8. Any analytical alteration degree 3 or 4 (scale AIDS Clinical Trials Group), confirmed, in the previous blood test taken before the ASC's first infusion.

1. Embarazo, lactancia, o negativa al uso de métodos anticonceptivos de eficacia probada tanto en hombres como en mujeres.
2. Infecciones oportunistas en tratamiento.
3. Coinfecciones activas por los virus B y C de la hepatitis
4. Cirrosis hepática estadio C de la clasificación de Child Pugh de cualquier etiología.
5. Hipertensión portal y/o hiperesplenismo de cualquier etiología.
6. Presencia de neoplasias malignas.
7. Tratamiento en los últimos doce meses con esteroides, inmunomoduladores, interferón, quimioterápicos o cualquier fármaco que pueda repercutir en la cifra de CD4.
8. Cualquier alteración analítica grado 3 o 4 (escala AIDS Clinical Trials Group), confirmada, en la analítica previa a la primera infusión de CeTMAd.

E.5 End points

E.5.1

Primary end point(s)

Safety:
- Incidence of adverse events grade 3 and 4, "Division of aids table for grading the severity of adult and pediatric adverse events". Publish Date: December, 2004.
- Incidence of opportunistic diseases.
Efficacy:
- Changes in the recount of CD4 + T / ul and CD4 + / CD8 + over 48 weeks.

De seguridad:
- Incidencia de efectos adversos grado 3 y 4, incluyendo los relativos a alteraciones de parámetros de laboratorio, para los que se utilizará la escala. ?Division of aids table for grading the severity of adult and paediatric adverse Events?. Publish Date: December, 2004.
- Incidencia de enfermedades oportunistas.
De eficacia:
- Evolución en el recuento de células T CD4+/µl y del cociente CD4+/CD8+ a lo largo de 48 semanas.

E.5.1.1

Timepoint(s) of evaluation of this end point

96 weeks

96 semanas

E.5.2

Secondary end point(s)

1. Identification and recount of different cell subpopulations CD4 +, CD8 +, NK and ? ? .
2. Phenotype of different cell subpopulations
3. Soluble mediators.
4. Specific immune response against HIV-1
5. Quantitation of HIV-1 viremia.
6. Quantification of proviral DNA.
7. Microbial translocation.

1. Identificación y contaje de distintas subpoblaciones celulares T CD4+, CD8+, NK y ??, además de células B, células dendríticas mieloides y células plasmocitodies y NK.
2. Fenotipo de las distintas subpoblaciones celulares
3. Mediadores solubles.
4. Respuesta inmune específica frente a VIH-1
5. Cuantificación de la viremia de VIH-1.
6. Cuantificación de la ADN proviral.
7. Translocación microbiana.

E.5.2.1

Timepoint(s) of evaluation of this end point

96 weeks

96 semanas

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

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Proof of concept

Prueba de concepto

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

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

Última visita de seguimiento del último paciente

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

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)

Monitoring as usual clinical practice

Seguimiento según práctica clínica habitual

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

2016-06-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-07-30

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