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Summary
EudraCT Number:	2012-003139-50
Sponsor's Protocol Code Number:	Maxillo1
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2013-08-21
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

A. Protocol Information

A.1

Member State Concerned

Norway - NOMA

A.2

EudraCT number

2012-003139-50

A.3

Full title of the trial

International, multicenter phase II uncontrolled prospective clinical trial:
Jaw bone reconstruction using a combination of biomaterial and autologous mesenchymal stem cells prior to dental implant placement
ImBioCeSM: Implant placement after reconstruction with a Biomaterial and mesenchymal stem cell combination

A.3.1

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

International trial. Reconstruction of jaw bone with a combination of biomaterial and autologous stem cells, before dental implant placement.

A.3.2

Name or abbreviated title of the trial where available

Maxillo 1

A.4.1

Sponsor's protocol code number

Maxillo1

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	University of Bergen, Faculty of medicin and dentistry, Dep. of Clinical Dentistry
B.1.3.4	Country	Norway
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	University of Bergen, Faculty of medicin and dentistry, Department of Clinical Dentistry
B.4.2	Country	Norway
B.4.1	Name of organisation providing support	Haukeland University Hospital, Clinical Trial Unit
B.4.2	Country	Norway
B.4.1	Name of organisation providing support	Institute for Clinical Transfusion Medicine and Immunogenetic
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Biomatlante
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Department of Clinical Dentistry, University of Bergen
B.5.2	Functional name of contact point	Sølve Hellem
B.5.3	Address:
B.5.3.1	Street Address	Aarstadveien 19
B.5.3.2	Town/ city	Bergen
B.5.3.3	Post code	5009
B.5.3.4	Country	Norway
B.5.4	Telephone number	+47NA55586655NA
B.5.5	Fax number	+47NA55586609NA
B.5.6	E-mail	solve.hellem@iko.uib.no

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	Mesenchymal stem cells and microporous Bi-phasic calcium phosphate (MBCP)
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Periodontal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	EX VIVO CULTURED HUMAN MESENCHYMAL STEM CELLS
D.3.9.4	EV Substance Code	SUB27304
D.3.10	Strength
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	100x10000000msc
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)	Yes
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

Men and women aged 18 years or more requiring jaw bone reconstruction prior to dental implant placement based on clinical and radiological examinations (CBCT Cone beam CT imaging). Areas suitable for reconstruction correspond to the mandible areas behind the canine teeth affected by lateral or vertical bone loss (focusing lateral bone loss). They must receive clear information about the study and give their informed consent to participate in the study.

E.1.1.1

Medical condition in easily understood language

Men and women aged 18 years or more requiring jaw bone reconstruction prior to dental implant placement. They must receive information, and sign informed consent to participate in the study.

E.1.1.2

Therapeutic area

Diseases [C] - Mouth and tooth diseases [C07]

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

The principal objective is to assess it is possible to insert an implant in the reconstructed area 4 months after the grafting procedure. The decision will be made based on a clinical and radiological examination.

E.2.2

Secondary objectives of the trial

The following secondary objectives will be assessed based on:
Clinical results
Subjective clinical appraisal of the quality of the newly formed bone after incision of the mucosa before implant placement (using the Likert scale)
Implant stability measurement the using the Ostell /ISQ system
Evaluation of pain, scar, functional limitations
Evaluation of study related complications.
Radiological results
Height and width of the reconstructed ridge
Quality of the newly formed bone (centralized biopsies analysis)
Histological results
Qualitative / quantitative assessment of the newly formed bone(centralized biopsies analysis )

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Local criteria:
o Patients presenting with an indication for an implant and wanting implant-borne prosthetic
restoration.
o Patients presenting with lateral or vertical bone loss (focusing lateral bone loss) of the mandible
behind the canine tooth.
o Lateral (width 5 mm or less) bone loss preventing the insertion of an implant without prior bone
augmentation.
o Endentate for more than 6 months in the region requiring reconstruction.
o Endentate concerning at least 2 missing teeth in the region requiring reconstruction.
o Absence of clinical signs of infection in the region requiring reconstruction.
o Patients presenting with good dental hygiene (subjective criteria)
o Patients not presenting with any major oral pathologies.
o Dental crest size less than 5 mm.
General criteria:
o Adult patients over 18 and under 80 years of age.
o Patients in good general health presenting with a complete blood count and renal and hepatic
function values within normal limits (confirmed by local laboratory tests).
o Patients with the capacity to understand medical information and give their informed consent.

E.4

Principal exclusion criteria

Local criteria:
o Patients presenting with clinical or radiological signs of bone infection (acute or chronic
osteomyelitis).
o Residual dentition close to the area requiring reconstruction with untreated endodontic disorder
(apical granuloma or apical cyst).
o Untreated oral infection (cellulitis, periodontitis).
o Patients with poor hygiene (subjective criteria).
o Surgical procedure undertaken in the area requiring reconstruction less than 6 months prior to
the bone graft.
o History of malignant tumors of the upper airways / digestive tract or of the jaw.
o History of or scheduled cervico-facial radiation therapy.
General criteria :
o the patient suffer from any serious coagulation disorders that could require substitution therapy
o the patient is receiving VKA therapy, which should be adjusted if necessary so that the INR does
not exceed 2.5
o the patient has history of allergy to iodine or to local anesthetics (sulfites, etc.)., or a history of
hematoma, or hemorrhage or blood coagulation disorders
o the patient has received localized iliac crest radiotherapy contraindicating withdrawal from the
irradiated site
o the patient has major skin lesions or diseases.
o Patients presenting with bone metabolism disorders: hypophosphatemia, primary parathyroid
osteitis or that is secondary to chronic renal insufficiency or osteomalacia, Paget’s disease,
vitamin D-related disorders, osteoporosis.
o Pregnant or breastfeeding women or women not using effective contraception if they are of
childbearing age.
o Patients presenting with cancerous disorders (carcinoma, sarcoma, leukemia, lymphoma) or
psychiatric disorders or with uncontrolled systemic diseases (diabetes, hypertension), or chronic
renal disease.
o Severe bruxism.
o History of chemotherapy.
o Smoking or alcohol addiction. Occasional consumption of alcohol and/or smoking will be noted
in the case report form.
o Patients with an ASA score of 0 or 1, incapable of tolerating general anesthesia.
o Immunosuppression
o Body mass index outside the normal range, particularly > 30 because of increased surgical risk
at the time of BM harvesting from the iliac crest.
o Risk of remote infection (orthopedic prosthesis implanted in the previous 6 months, patients
presenting with a high risk of infective endocarditis, presence of pulmonary arteriovenous shunt,
etc.).
o HIV, HTLV and/or syphilis seropositivity.
o Hepatitis B or C infection.
o Active autoimmune disease.
o History of immunosuppressant treatment or bone marrow treatment.
o Administration of treatment interfering with bone metabolism.
o Patients requiring antibiotic prophylaxis before any dental procedure
o Concomitant treatments: history of treatment or current treatment with bisphosphonates, long
term corticosteroid treatment.
o Minor(s) or persons of full age under tutorship.
Tests are left to the discretion of the physician

E.5 End points

E.5.1

Primary end point(s)

At the end of the healing period (4-6 months), radiological and clinical examinations will be performed to determine whether or not the patient may have one or more implants inserted.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 4-6 months.

E.5.2

Secondary end point(s)

Clinical and radiological follow-up is programmed for 12 months after the implant loading. It includes subjective satisfaction assessment, a clinical examination, implant stability measurement by Resonance Frequency Analysis and x-ray examination of the
implant.

E.5.2.1

Timepoint(s) of evaluation of this end point

After 19 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

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.8.2.4

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

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

F.4.2.2

In the whole clinical trial

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)

Standard operating procedure for these patients.

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

2014-01-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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

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