Clinical Trials Register

Summary
EudraCT Number:	2015-000431-32
Sponsor's Protocol Code Number:	ORTHOUNION
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-04-04
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

France - ANSM

A.2

EudraCT number

2015-000431-32

A.3

Full title of the trial

A MULTI-CENTRE, OPEN-LABEL, RANDOMIZED, COMPARATIVE CLINICAL TRIAL OF TWO DIFFERENT DOSES OF BONE MARROW AUTOLOGOUS HUMAN MESENCHYMAL STEM CELLS PLUS BIOMATERIAL VERSUS ILIAC CREST AUTOLOGOUS GRAFT, FOR BONE HEALING IN NON-UNION AFTER LONG BONE FRACTURES.

ESSAI CLINIQUE COMPARATIF MULTICENTRIQUE, OUVERT, RANDOMISE, DE DEUX DOSES DIFFÉRENTES DE CELLULES SOUCHES MÉSENCHYMATEUSES HUMAINES AUTOLOGUES DE MOELLE OSSEUSE ASSOCIÉES A UN BIOMATÉRIAU, VERSUS GREFFE AUTOLOGUE DE CRÊTE ILIAQUE, POUR LA RÉPARATION OSSEUSE DE FRACTURES NON CONSOLIDÉES DES OS LONGS

A.3.1

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

A COMPARATIVE STUDY OF TWO DIFFERENT DOSES OF BONE MARROW AUTOLOGOUS HUMAN MESENCHYMAL STEM CELLS PLUS BIOMATERIAL VERSUS ILIAC CREST AUTOLOGOUS GRAFT, FOR BONE HEALING IN NON-UNION AFTER LONG BONE FRACTURES

Comparaison de deux doses différentes de cellules souches mésenchymateuses humaines autologues de moelle osseuse associées à un biomatériau, versus greffe autologue de crête iliaque, pour la réparation osseuse de fractures non consolidées des os longs

A.3.2

Name or abbreviated title of the trial where available

ORTHOUNION

A.4.1

Sponsor's protocol code number

ORTHOUNION

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	Universidad Autónoma de Madrid (U.A.M.)
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	European Comission (Horizon 2020)
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	Departamento de Farmacología Clínica-Universitary Hospital Puerta de Hierro Majadahonda
B.5.2	Functional name of contact point	Cristina Avendaño-Sola
B.5.3	Address:
B.5.3.1	Street Address	c/Manuel de Falla 1. Hospital Puerta de Hierro Majadahonda. Servicio de Farmacología Clínica
B.5.3.2	Town/ city	Majadahonda-Madrid
B.5.3.3	Post code	28220
B.5.3.4	Country	Spain
B.5.4	Telephone number	34911916479
B.5.5	Fax number	34911917650
B.5.6	E-mail	cristina.avendano@uam.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	Cultured Mesenchymal Cells from bone marrow isolation-Low Dose
D.3.2	Product code	Low Dose BM-MSCs
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	Intraosseous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Autologous Mesenchymal Stem Cells
D.3.9.2	Current sponsor code	Low dose BM-MSCs
D.3.9.3	Other descriptive name	HUMAN AUTOLOGOUS MESENCHYMAL STEM CELLS
D.3.9.4	EV Substance Code	SUB180295
D.3.10	Strength
D.3.10.1	Concentration unit	CFU/ml colony forming unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10000000
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Yes
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	Cultured Mesenchymal Cells from bone marrow isolation-High Dose
D.3.2	Product code	High Dose BM-MSCs
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	Intraosseous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Autologous Mesenchymal Stem Cells
D.3.9.2	Current sponsor code	High dose BM-MSCs
D.3.9.3	Other descriptive name	HUMAN AUTOLOGOUS MESENCHYMAL STEM CELLS
D.3.9.4	EV Substance Code	SUB180295
D.3.10	Strength
D.3.10.1	Concentration unit	CFU/ml colony forming unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20000000
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Yes
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

Diaphyseal and/or metaphysodiaphyseal fractures (femur, tibia, humerus) with status of non-union

Fractures diaphysaires et/ou métaphyso-diaphysaires (fémur, tibia, humérus) non consolidées

E.1.1.1

Medical condition in easily understood language

Long bones (femur, tibia, humerus) fractures with non-union

Fractures des os longs (fémur, tibia, humérus) non consolidées

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10028395
E.1.2	Term	Musculoskeletal and connective tissue disorders
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10017085
E.1.2	Term	Fracture malunion
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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 determine if the combined treatment of hBM-MSC+Biomaterial(G2) is superior to Iliac Crest Autologous Graft(G1) to obtain bone consolidation at 12 months after surgery of diaphyseal and/or metaphysodiaphyseal fractures (femur, tibia, humerus) with status of non-union (more than 9 months after the acute fracture)

Déterminer si le traitement combiné de hBM-MSC + Biomatériau (G2) est supérieur à la greffe autologue de crête iliaque (G1) pour obtenir une consolidation osseuse (clinique et radiologique) 12 mois après la chirurgie de fractures diaphysaires et / ou métaphyso-diaphysaires (fémur, tibia, humérus) ayant un statut de non-consolidation (après plus de 9 mois depuis la fracture aiguë)

E.2.2

Secondary objectives of the trial

* Compare % bone consolidation between G1 and G2 arms at 6 and 24 months after surgery (m. aft. surg.)
* Compare, G1 and G2 arms, at 6, 12 and 24 m. aft. surg., the following:
- Radiological consolidation with REBORNE-scale
- Pain w/ and w/o weight bearing
- Rate of re-intervention in the callus
- Complication rate
- Assess safety of autologous hBM-MSCs
- Physical & mental health status
* Identify associated factors to bone consolidation (time from the acute fracture, type of prior-surgery, severity, and country)
and
* Determine if G2b is non-inferior to G2a to obtain radiological consolidation at 12 months after surgery.
* Compare radiological consolidation, w/ REBORNE-Scale, between G2a and G2b arms at basal, 24 and 96 w. aft. surg.
* Compare, between G2a and G2b arms, at 6, 12 and 24 m. aft. surg., the following:
- % bone consolidation
- Pain w/ and w/o weight bearing
- Rate of re-intervention in the callus
- Complication rate
- Physical & mental health status

* Comparer le % de consolidation entre G1 et G2 à 6 et 24 mois après la chirurgie (m.ap.chir.)
* Comparer entre G1 et G2 à 6, 12 et 24 m.ap.chir. :
- consolidation radiologique (REBORNE)
- douleur avec et sans mise en charge.
- taux de ré-intervention .
- taux de complication.
- sécurité des hBM-MSC autologues.
- statutphysique et mental
* Identifier les facteurs associés à la consolidation osseuse (délai depuis la fracture aiguë, type de chirurgie antérieure, gravité et pays).
*Déterminer si G2b n'est pas inférieur à G2a pour obtenir une consolidation radiologique à 12 m.ap.chir.
* Comparer le % de consolidation entre les bras G2a et G2b à 6 et 24 mois après la chirurgie (m.ap.chir.)
* Comparer entre G2a et G2b à 6, 12 et 24 m.ap.chir. :
- consolidation radiologique (REBORNE).
- douleur avec et sans mise en charge.
- taux de ré-intervention .
- taux de complication.
- état physique et mental

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

To be eligible to enter the study candidates must satisfy all of the following criteria:
1. Age 18 and older, both sexes
2. Traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union. A non-union is defined as a fracture not healed at least 9 months after the originating trauma, that meets the following criteria (Weber 1986):
‐ Insufficient bone bridging to stabilize the fracture
‐ Insufficient bone biological activity in the fracture
‐ Failure of previous treatments

3. Able to understand, accept and sign informed consent
4. Medical health coverage
5. Able to understand and accept the study constraints. In case of doubts, particularly in elderly patients, a specific capacity test (e.g., Mini-mental State Examination, MMSE (Appendix 8)) will be performed.

1. Âge 18 et plus, les deux sexes
2. Fracture traumatique isolée fermée ou ouverte Gustilo I et II, IIIA et IIIB humérus, tibia tibiale ou fémorale diaphysaire ou métaphysodiaphysaire avec statut de non-consolidation atrophique, oligotrophique ou normotrophique. Une non-consolidation est définie comme une fracture non guérie au moins 9 mois après le traumatisme d'origine, qui répond aux critères suivants (Weber, 1986):
- Un pontage osseux insuffisant pour stabiliser la fracture
- Activité biologique osseuse insuffisante dans la fracture
- L'échec des traitements précédents

3. Capable de comprendre, d'accepter et de signer le consentement éclairé
4. Couverture médicale
5. Capable de comprendre et d'accepter les contraintes de l'étude. En cas de doute, en particulier chez les patients âgés, un test de capacité spécifique (par exemple, mini-examen de l'état mental, MMSE (Annexe 8)) sera effectué.

E.4

Principal exclusion criteria

1. Hypertrophic non-unions
2. Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc)
3. Unrecovered vascular or neural injury
4. Other fractures causing interference with weight bearing
5. Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.)
6. Active infection of any location and aetiology
7. Surgical contraindication of any cause
8. Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control. The following methods are considered adequate:
‐ Combined hormonal contraception
‐ Injected hormonal contraception
‐ Implanted hormonal contraception
‐ Progesterone-only hormonal contraception associated with inhibition of ovulation
‐ Placement of an intrauterine device (IUD)
‐ Placement of intrauterine hormone-realising system (IUS)
-Sexual abstinence
9. Malignant tumor (past history or concurrent disease)(except carcinoma in situ or basalioma in remission)
10. History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection
11. Insulin dependent diabetes
12. Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection
13. Any evidence of Syphilis
14. Known allergies to products involved in the production process of MSC
15. Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
16. Autoimmune inflammatory disease
17. Current treatment by biphosphonates not stopped three months prior to study inclusion
18. Impossibility to meet at the appointments for the follow up
19. Participation in another therapeutic trial in the previous 3 months
20. Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)

1. Non-consolidations hypertrophiques
2. Perte osseuse segmentaire nécessitant une thérapie spécifique (transport osseux, greffe vascularisée, grande allogreffe structurelle, mégaprothèse, etc.)
3. Blessure vasculaire ou vasculaire non récupérée
4. Autres fractures causant des interférences avec le poids
5. Lésions viscérales ou les maladies qui interfèrent avec la formation de cal (traumatisme cranioencephalique sévère, etc.)
6. Infection active
7. Contre-indication chirurgicale de toute cause
8. Grossesse, allaitement maternel et les femmes en âge de procréer et n’étant pas sous contraception adéquate. Les méthodes suivantes sont considérées comme adéquate: contraception hormonale combinée; Contraception hormonale injectée; Contraception hormonale implantée; Contraception hormonale à la progestérone seule associée à une inhibition de l'ovulation; Mise en place d'un dispositif intra-utérin (DIU); Mise en place du système hormonal intra-utérin (SIU); Abstinence sexuelle
9. Tumeur maligne (antécédents ou maladie concomitante) (à l'exception du carcinome in situ ou du basaliome en rémission)
10. Historique de prélèvement osseux sur la crête iliaque contre-indiquant une greffe osseuse à partir de la crête iliaque nouvelle ou le prélèvement de moelle osseuse
11. Diabétique insulinodépendant
12. Toute preuve (confirmée par PCR) d'une infection active par le VIH, une hépatite B ou une infection à l'hépatite C ou une syphilis
14. Allergies connues aux produits impliqués dans le processus de production du MSC
15. Traitement de type corticoïde ou immunosuppresseur plus d'une semaine au cours des trois mois précédant l'inclusion dans l'étude
16. Maladie inflammatoire auto-immune
17. Traitement actuel par les biphosphonates, non arrêté trois mois avant l'inclusion de l'étude
18. Impossibilité de respecter les rendez-vous pour le suivi
19. Participation à un autre essai thérapeutique au cours des trois mois précédents
20. Deuxième non-consolidation en cas de non-consolidation bilatérale ou multiple (une seule non-consolidation par patient sera admise dans l'étude)

E.5 End points

E.5.1

Primary end point(s)

The percentage of patients with bone consolidation (Yes/No) in the G1 (comparator) and G2 (experimental) treatment arms at 12 months after the surgery. A superiority test will compare this endpoint in both treatment arms. Each endpoint will be estimated as the number of bone consolidations in each arm, over the total number of treated patients in each arm.
For this first primary endpoint, bone consolidation will be considered achieved when all three of the following criteria are met:
a) Radiographic bone bridging: New bone formation across the fracture site visible in 3/4 cortices, on at least 3/4 views (Front views: Internal and external cortical; Lateral views: Anterior and Posterior cortical).
b) Clinical healing: Pain equal or less than 3 in a Numeric Rating Scale (NRS, 0 to 10) for pain during full weight-bearing and without weight bearing.
c) No further surgical intervention in the callus site: mayor surgery will be considered either as nail replacement, plate replacement, or replacement of all components of the previous surgery.

Le critère de jugement principal est le pourcentage de consolidation osseuse (Oui / Non) dans le bras de traitement G1 (comparateur: autogreffe de crête iliaque) et G2 (expérimental: hBM-MSC) à 12 mois après la chirurgie. Les deux bras de traitement seront comparés avec un test de supériorité (delta ciblé de 20%). C'est le critère d'évaluation principal et il sera estimé comme le nombre de consolidation osseuse dans chaque bras, par rapport au nombre total de patients traités dans chaque bras.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months after surgery

E.5.2

Secondary end point(s)

EFFICACY ENDPOINTS:
** G1/G2 arms
- Percentage of patients with bone consolidation (Yes/No) in the G1 and G2 treatment arms at 6 and 24 months after surgery. Estimated as the number of bone consolidations in each arm, over the total number of treated patients in each arm. For this endpoint, bone consolidation was defined as previously established for the primary endpoint.
- Radiological punctuation score using the REBORNE-Scale in the G1 and G2 treatment arms of treatment at 6, 12 and 24 months after surgery calculated in xR images (and/or CT for ratify purpose).
- Pain scale value in the G1 and G2 treatment arms at basal baseline, 6, 12 and 24 months after surgery, using the Numeric Rating Scale (NRS) for pain (from 0 to 10).
- Rate of reoperation in the callus site in G1 and G2 arms of treatment arms at 6, 12 and 24 months after surgery.
- Average percentage of the Short Form-36 Health Survey at baseline, 6, 12 and 24 months after surgery.

** G2b/G2a arms:
- Radiological score in the G2a (High dose of hBM-MSC+Biomaterial) and G2b (Low dose of hBM-MSC+Biomaterial) treatment arms at 12 months after surgery. This endpoint will be calculated using the REBORNE-Scale, which can obtain a score ranging from 0 to 1. The score will be calculated in xR images (and/or CT for ratify ratification purposes) using a specific formula.
- Radiological score using the REBORNE-Scale in the G2a and G2b treatment arms at 6 and 24 months after surgery calculated in XR images (and/or CT for ratify purpose).
- Percentage of bone consolidation (Yes/No) in the G2a and G2b treatment arms at 6, 12 and 24 months after surgery. Estimated as the number of bone consolidations in each arm, over the total number of treated patients in each arm . For this endpoint, bone consolidation was defined as previously established for the primary endpoint.
- Pain scale value in the G2a and G2b treatment arms at baseline, 6, 12 and 24 months after surgery, using Numeric Rating Scale (NRS) for pain (from 0 to 10).
- Rate of reoperation in the callus site in the G2a and G2b treatment arms of treatment at 6, 12 and 24 months after surgery.
- Average percentage of the Short Form-36 Health Survey at baseline, 6, 12 and 24 months after surgery.

SAFETY ENDPOINTS:
** G1/G2 arms:
Safety endpoints will be estimated in the G1 and G2 treatment arms and includes:
a) Early local complication rate, as percentage of patients with local complications within three months after surgery.
b) Global complication rate, as percentage of patients with local or general complications regarding potential effects of the treatment at 6, 12 and 24 months after surgery.
For early and global complications we will specifically investigate:
- Adverse event related to the product application process (surgical or other, including the bone marrow harvesting process or the iliac crest graft)
- Local heterotopic ossification
- Local bone resorption
- Local osteolysis
- Local and general infection
- Vascular complication (ischemia, phlebitis)
- Neurological problems
- Unexpected events (e.g. hypersensitivity, immunological, toxic or other)
- Adverse events related to mandatory concomitant medication (e.g. anaesthetics)

** G2b/G2a arms:
Safety endpoints (early complication rate and global complication rate) will be compared in the G2a and G2b of treatments arm as described above (for the G1-G2 arm comparison).

CRITERES D’EFFICACITE
- Score de consolidation radiologique
- Score radiologique à l'aide de l'Échelle REBORNE
- Pourcentage de consolidation.
- Score de l'échelle de la douleur
- Taux de ré-intervention au niveau du cal osseux formé à 6, 12 et 24 mois après la chirurgie.
- Variation moyenne du score de qualité de vie SF-36 entre T0, 6, 12 et 24

CRITERES DE SECURITE
- Taux de complication locale précoce dans les trois mois suivant la chirurgie.
- Taux global de complication 6, 12 et 24 mois après la chirurgie.

E.5.2.1

Timepoint(s) of evaluation of this end point

6 and 24 months after surgery, in some items, and 6, 12 and 24 months, in other.

6 et 24 mois après la chirurgie, pour certaines variables, et 6, 12 et 24 mois, pour d'autres

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Autologous graft harvested from the iliac crest

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

108

F.4.2.2

In the whole clinical trial

108

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)

If bone healing has not occurred, the patient may require additional treatment and an additional follow-up, under the care of the Hospital, the treating physician or service, or the provider in charge of his process, even if unrelated to the study.

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	ECRIN

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-05-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-13

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

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:
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