Evaluation of EpiBone-CMF for Mandibular Ramus Reconstruction

NCT ID: NCT03678467

Last Updated: 2022-05-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-31

Study Completion Date

2023-11-30

Brief Summary

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EpiBone-Craniomaxillofacial (EB-CMF) is an autologous, anatomically shaped bone graft created specifically for the patient's defect, using the patients own adipose-derived mesenchymal stem cells. This first in human trial is designed specifically to assess the safety of EB-CMF clinically. Although secondary measures of graft efficacy are being assessed, the primary focus will be on Adverse Events stemming from graft implantation.

Detailed Description

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Conditions

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Mandible Tumor Mandibular Injuries Mandible; Deformity

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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EB-CMF Implant

Subject receiving EB-CMF implant

Group Type EXPERIMENTAL

EB-CMF

Intervention Type COMBINATION_PRODUCT

Autologous, anatomically shaped bone graft

Interventions

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EB-CMF

Autologous, anatomically shaped bone graft

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

1. Patients must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
2. Stable mandibular ramus injury or defect due to trauma, disease, or congenital defects.
3. Medical history must be verified by either a personal physician or medical practitioner as appropriate.
4. Patient determined by the Investigator to be a suitable candidate by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation.
5. A female patient is eligible to participate if she is not pregnant (see Appendix 6), not breastfeeding, and at least 1 of the following conditions applies:

1. A woman of nonchildbearing potential (WONCBP) as defined in Appendix 6. OR
2. A woman of childbearing potential (WOCBP) who agrees to follow the contraceptive guidance in Appendix 6 for at least 1 month prior to surgery, during the treatment period, and until 12 weeks after completion of the study.
6. Patient must be available at the study center for all specified assessments throughout the study duration.
7. Patients whose clinical laboratory test results are within the reference range for healthy individuals, or where outside the reference range is judged as not clinically relevant by the Investigator.
8. All patients are required to give written informed consent as described in Appendix 2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, and in accordance with the Declaration of Helsinki, before enrollment. Patients must provide written informed consent and authorization for use and disclosure of protected health information.
9. A healthy condyle which can be plated with titanium plates and screws.
10. A mandibular continuity ramus defect which starts below the sigmoid notch and extends only as far as but not including the angle.

Exclusion Criteria

1. Uncontrolled alcohol, tobacco, or substance abuse within 6 months prior to implantation.
2. Mandibular ramus defects with open wounds.
3. Defects \> 15 cc in volume.
4. Defects \> 6 cm in diameter.
5. Systemic disease that would render the fat harvest and product implantation, along with associated anesthesia, unsafe to the patient.
6. Patient has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would impact patient safety or interfere with the integrity of the study data.
7. Active uncontrolled infection or malignancy. Patients will be allowed to undergo rescreening once, after the infection is cleared, if they are willing to do so.
8. Patients with signs and symptoms of infection between Screening and up to the surgical implantation.
9. Radiation therapy \< 6 months prior to the surgical implantation.
10. Need for soft tissue reconstruction (flap, skin graft, etc).
11. Conditions that may impact the success of the surgical implantation or increase the risk of postoperative complications, including inherited coagulopathies like hemophilia, Von Willebrand's disease, protein C and S deficiency, thrombocythemias, thallassemias, sickle cell disease, etc.
12. Conditions that may impact functional outcomes, including uncontrolled diabetes, osteoporosis, rare disorders of bone healing like osteopetrosis, or any other metabolic bone disease.
13. Increased alkaline phosphatase (to exclude Paget's disease), increased serum calcium (to exclude hyperparathyroidism), or Vitamin D deficiency, at Screening, confirmed by a repeat test.
14. Oral bisphosphonate \< 12 weeks, intravenous bisphosphonate \< 12 months prior to Screening or use of systemic steroids or anabolic agents (e.g. teriparatide) for osteoporosis treatment.
15. Patients with inadequate donor sites for lipoaspirate of adipose tissue.
16. Mixed connective tissue diseases and collagen diseases which can result in poor wound healing after surgery.
17. Patients considered unsuitable per the consulted surgeon.
18. Patient has any of the following conditions as identified by medical history:

1. Human immunodeficiency virus (active or seropositive).
2. Active tuberculosis.
3. Active hepatitis B infection.
4. Hepatitis C.
5. Viral encephalitis.
6. Toxoplasmosis. In case of doubt regarding mentioned conditions based on the physical examination or other signs or symptoms present at Screening, the patient will be asked to consent to additional testing to rule out such conditions or the patient must be excluded from the study.
19. Donation of blood and blood products is not permitted from Screening and for at least 3 months after the surgical implantation.
20. Patient participated in another clinical study of an investigational drug within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to the surgical implantation or is currently participating in another clinical study of an investigational drug or intending to participate in another clinical study of an investigational drug before completion of all scheduled evaluations in this clinical study.
21. Patients who, in the opinion of the Investigator, are not likely to complete the study for whatever reason.
22. The Investigator or any sub-investigator, research assistant, surgeon, study coordinator, or other staff directly involved in the conduct of the clinical study or any of their relatives.
23. Hypersensitivity to any product of bovine origin.
24. Hypersensitivity to gentamicin or other aminoglycosides.
25. Post-menopausal women who have an abnormally low bone mineral density or have not tested for bone mineral density.
26. Patients with discontinuity defects of the ramus.
27. Patients with a history of malignant cancer.
28. Hypersensitivity or allergy to epinephrine or other drugs commonly used during surgery.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Epibone, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brian R Gastman, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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VA Healthcare System, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

UT Health San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Brian R Gastman, MD

Role: CONTACT

216-444-9419

Facility Contacts

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Rebeka Silva, DMD, FACD

Role: primary

Beverly Doyle

Role: primary

Erin Locke, BSN, RN

Role: primary

References

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Bhumiratana S, Bernhard JC, Alfi DM, Yeager K, Eton RE, Bova J, Shah F, Gimble JM, Lopez MJ, Eisig SB, Vunjak-Novakovic G. Tissue-engineered autologous grafts for facial bone reconstruction. Sci Transl Med. 2016 Jun 15;8(343):343ra83. doi: 10.1126/scitranslmed.aad5904.

Reference Type BACKGROUND
PMID: 27306665 (View on PubMed)

Bhumiratana S, Vunjak-Novakovic G. Concise review: personalized human bone grafts for reconstructing head and face. Stem Cells Transl Med. 2012 Jan;1(1):64-9. doi: 10.5966/sctm.2011-0020. Epub 2011 Dec 7.

Reference Type BACKGROUND
PMID: 23197642 (View on PubMed)

Grayson WL, Marolt D, Bhumiratana S, Frohlich M, Guo XE, Vunjak-Novakovic G. Optimizing the medium perfusion rate in bone tissue engineering bioreactors. Biotechnol Bioeng. 2011 May;108(5):1159-70. doi: 10.1002/bit.23024. Epub 2010 Dec 22.

Reference Type BACKGROUND
PMID: 21449028 (View on PubMed)

Grayson WL, Bhumiratana S, Cannizzaro C, Vunjak-Novakovic G. Bioreactor cultivation of functional bone grafts. Methods Mol Biol. 2011;698:231-41. doi: 10.1007/978-1-60761-999-4_18.

Reference Type BACKGROUND
PMID: 21431523 (View on PubMed)

Related Links

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Other Identifiers

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EB-CMF-02

Identifier Type: -

Identifier Source: org_study_id

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