Clinical Trials Register

Summary
EudraCT Number:	2012-005599-33
Sponsor's Protocol Code Number:	AMSC-BDT-001
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-02-04
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

Czechia - SUKL

A.2

EudraCT number

2012-005599-33

A.3

Full title of the trial

Utilization of Autologous Multipotent Mesenchymal Stem Cells in the Management of the Large Skeletal Defects during Revision Total Hip Arthroplasty: a Prospective, Non-randomized, Open-Label Study to Assess the Safety and the Efficacy.

Využití autologních multipotentních mesenchymálních kmenových buněk k léčení rozsáhlých defektů skeletu při reimplantaci totální endoprotézy kyčelního kloubu: prospektivní, nerandomizovaná studie k hodnocení bezpečnosti a účinnosti.

A.3.1

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

Safety and Efficacy of Biomaterial with Autologous Stem Cells in Management of Total Hip Prosthesis Revision.

Bezpečnost a účinnost biomateriálu s autologními kmenovými buňkami při reimplantaci totální endoprotézy kyčelního kloubu.

A.3.2

Name or abbreviated title of the trial where available

Autologous MCS in Bone Defect Treatment

A.4.1

Sponsor's protocol code number

AMSC-BDT-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	Lékařská fakulta Univerzity Karlovy v Hradci Králové
B.1.3.4	Country	Czech Republic
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	IGA MZ ČR
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bioinova, s.r.o.
B.5.2	Functional name of contact point	Petr Bažant, CEO
B.5.3	Address:
B.5.3.1	Street Address	Vídeňská 1083
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	142 20
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	00420224436782
B.5.5	Fax number	00420224436799
B.5.6	E-mail	bazant@biomed.cas.cz

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	Suspension of human autologous MSC 3P in 1.5 ml
D.3.2	Product code	AMSC
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	Implantation
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Human Autologous Mesenchymal Stem Cells
D.3.9.2	Current sponsor code	AMSC
D.3.10	Strength
D.3.10.1	Concentration unit	million organisms/ml million organisms/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	7 to 13
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)	Yes
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Revision total hip arthroplasty.

Reimplantace totální endoprotézy kyčelního kloubu.

E.1.1.1

Medical condition in easily understood language

Re-operation for total hip joint prosthesis.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10044088
E.1.2	Term	Total hip replacement
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The goal of this study is to assess the safety and the efficacy of beta-tricalcium phosphate biomaterial containing autologous mesenchymal stem cells.
Primary Objective - Safety:
To document absence of complications at the site of femoral bone defect. To assess overall profile of untoward events in study subjects.

Cílem této studie je zhodnocení bezpečnosti a účinnosti beta-trikalcium fosfátového biomateriálu obsahujícího autologní mezenchymální kmenové buňky při léčení kostních defektů.
Primární cíl - bezpečnost:
Ověření absence komplikací v místě ošetřeného kostního defektu stehenní kosti, dále zhodnocení případných celkových zdravotních komplikací pacientů.

E.2.2

Secondary objectives of the trial

Safety: Incidence of other study treatment-emergent adverse events. Overall safety.
Efficacy: To assess the quality of healing of femoral bone defects as evaluated by Harris Hip Score, plain X-rays and densitometry, in comparison to referral data.

Bezpečnost: Výskyt nepříznivých událostí koincidujících s hodnocenou léčbou. Celková bezpečnost.
Účinnost: Hodnocení kvality hojení kostních defektů stehenní kosti pomocí Harrisova kyčelního skóre, rentgenových snímků a denzitometrie, srovnání s referenčními daty.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To participate in this trial, patients have to meet following criteria:
1. established diagnosis of aseptic loosening of a total hip arthroplasty indicated for revision hip surgery,

2. subjects with extensive femoral bone defects,

3. age between 18 –75 years, both sexes, and
- for subjects aged 18 to 65 years: ASA score I to III *,
- for subjects aged 66 to 75 years: ASA score I to II *,

4. able to provide written informed consent.

(*) ASA score: A physical status classification system of the American Society of Anesthesiologists for assessing the fitness of patients before surgery.

E.4

Principal exclusion criteria

Patients meeting any of the following criteria shall not be allowed to participate in this study:

1. previous infection at the site of total hip arthroplasty,

2. rheumatoid arthritis,

3. pregnancy or breastfeeding

4. women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners,

5. fertile men not using proven contraceptive measures including effective contraception method (established oral contraception, intrauterine device, ligation of the uterine tube) in their partner,

6. skin infection at the site of bone marrow aspiration or at the site of total hip arthroplasty,

7. malnutrition, primary biliar cirrhosis

8. any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, systemic infection, ...),

9. alcohol or drug abuse,

10. cancer (compulsory clinical oncological screening),

11. osteonecrosis of pelvis and hip due to past radiation treatment

12. ongoing and recent (last 3 months) systemic corticosteroid or immunosuppressive therapy.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
Safety: To assess an absence of complications at the site of revision total hip arthroplasty.

Primární koncový bod:
Bezpečnost: Hodnocení nepřítomnosti komplikací v oblasti revizní totální endoprotézy kyčelního kloubu.

E.5.1.1

Timepoint(s) of evaluation of this end point

At each visit since Visit V (1 days post-surgery) until Visit X (12 months postsurgery).

E.5.2

Secondary end point(s)

To assess the quality of life measured by Harris Hip Score and the quality of healing measured by plain X-rays and densitometry 12 month after surgery.

Hodnocení kvality života pomocí Harrisova kyčelního skóre a kvality hojení pomocí rentgenologického vyšetření (nativní snímky) a densitometrie za 12 měsíců po operaci

E.5.2.1

Timepoint(s) of evaluation of this end point

At Visit X (12 months postsurgery)

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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

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

Subjects scheduled for total hip endoprosthesis re-implantation and meeting inclusion/exclusion criteria will be assigned to autologous mesenchymal stromal cell (AMSC) treatment to heal femoral bone defects during the revision total hip arthroplasty. The subjects will be followed up for 1 year aftre the surgery and test product administration. When 19 such subjects have completed the study in this way, the trial will end.

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)

Not different from the expected normal follow up of patients with the studied condition (revision hip joint total replacement).

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

2013-06-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-11-17

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