Evaluation of EpiBone-CMF for Mandibular Ramus Reconstruction

NCT03678467 | Unknown Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: EB-CMF-02
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Mandible Tumor; Mandibular Injuries; Mandible; Deformity

Keywords

tissue engineering, tissue engineered product, mesenchymal stem cells

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events

  To assess the safety of EB-CMF for up to 12 months post surgery in subjects with recent or remote mandibular ramus defects requiring up to a 15 cc graft reconstruction.

  12 months

Secondary Outcomes (3)

• Bone regeneration as assessed by high-resolution CT scans

  12 months

• Quality of life as measured by the Glasgow Benefit Inventory

  12 months

• Quality of life as measured by SF-12

  12 months

Other Outcomes (1)

• Observational assessment of bone regeneration by high-resolution CT scan

  10 Years

Study Arms (1)

EB-CMF Implant

EXPERIMENTAL

Subject receiving EB-CMF implant

Combination Product: EB-CMF

Interventions

EB-CMF COMBINATION_PRODUCT

Autologous, anatomically shaped bone graft

EB-CMF Implant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Stable mandibular ramus injury or defect due to trauma, disease, or congenital defects.
• Medical history must be verified by either a personal physician or medical practitioner as appropriate.
• Patient determined by the Investigator to be a suitable candidate by medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation.
• 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:
• A woman of nonchildbearing potential (WONCBP) as defined in Appendix 6. OR
• 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.
• Patient must be available at the study center for all specified assessments throughout the study duration.
• 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.
• 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.
• A healthy condyle which can be plated with titanium plates and screws.
• A mandibular continuity ramus defect which starts below the sigmoid notch and extends only as far as but not including the angle.

You may not qualify if:

• Uncontrolled alcohol, tobacco, or substance abuse within 6 months prior to implantation.
• Mandibular ramus defects with open wounds.
• Defects \> 15 cc in volume.
• Defects \> 6 cm in diameter.
• Systemic disease that would render the fat harvest and product implantation, along with associated anesthesia, unsafe to the patient.
• 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.
• 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.
• Patients with signs and symptoms of infection between Screening and up to the surgical implantation.
• Radiation therapy \< 6 months prior to the surgical implantation.
• Need for soft tissue reconstruction (flap, skin graft, etc).
• 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.
• Conditions that may impact functional outcomes, including uncontrolled diabetes, osteoporosis, rare disorders of bone healing like osteopetrosis, or any other metabolic bone disease.
• 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.
• 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.
• Patients with inadequate donor sites for lipoaspirate of adipose tissue.

Sponsors & Collaborators

• Epibone, Inc.: lead

Study Sites (3)

VA Healthcare System, San Francisco

San Francisco, California, 94121, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

UT Health San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 27306665 BACKGROUND

• 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.

  PMID: 23197642 BACKGROUND

• 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.

  PMID: 21449028 BACKGROUND

• 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.

  PMID: 21431523 BACKGROUND

Related Links

• EpiBone, Inc.

MeSH Terms

Conditions

Mandibular Neoplasms; Mandibular Injuries; Congenital Abnormalities

Condition Hierarchy (Ancestors)

Jaw Neoplasms; Skull Neoplasms; Bone Neoplasms; Neoplasms by Site; Neoplasms; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Mandibular Diseases; Stomatognathic Diseases; Maxillofacial Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Brian R Gastman, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian R Gastman, MD

CONTACT

216-444-9419; gastmab@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2018
• First Posted: September 19, 2018
• Study Start: March 31, 2021
• Primary Completion: August 1, 2023
• Study Completion: November 1, 2023
• Last Updated: May 27, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

US (3)