Safety and Efficacy Evaluation of the Ivory Dentin Graft Device (IvoryGraft) - Long Term Follow-Up

• ClinicalTrials.gov Identifier: NCT04868825
• Recruitment Status: Active, not recruiting
• First Posted: May 3, 2021
• Last Update Posted: May 3, 2021
• Sponsor: Ivory Graft Ltd.
• Information provided by (Responsible Party): Ivory Graft Ltd.

Tracking Information

• First Submitted Date: April 20, 2021
• First Posted Date: May 3, 2021
• Last Update Posted Date: May 3, 2021
• Actual Study Start Date: November 7, 2017
• Estimated Primary Completion Date: January 10, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2021)

• Success of implant placement in a rigid post grafting site [ Time Frame: 5 years after grafting ]
  defined by dental implant survival
• Number of Participants with Treatment-Related Adverse Events [ Time Frame: 5 years after grafting ]
  through study completion

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Evaluation of the Ivory Dentin Graft Device (IvoryGraft) - Long Term Follow-Up
• Official Title: Safety and Efficacy Evaluation of the Ivory Dentin Graft Device - Long Term Follow-Up
• Brief Summary: long-term safety and performance of Ivory Dentin Graft. Ivory Dentin Graft is at least as good as the competitor treatment group (OsteoBiol Gen-Os) for alveolar ridge preservation following tooth extraction.

Detailed Description

This clinical investigation is part of the post-market development process of the investigational device of Ivory Graft Ltd. in order to satisfactory validate the safety, tolerability and effectiveness of Ivory Dentin Graft as required by the sponsor's European Union (EU) notified body.

The clinical Investigation was conducted with the stated confirmation applying European regulations; International Conference of Harmonization - Good Clinical Practice (ICH-GCP) guidelines, ISO 14155:2011, and with a relevant subject population for the study objectives. Israeli Ministry of Health registration Number: 20173907.

The purpose of this investigation is to evaluate the safety, tolerability and effectiveness of Ivory Dentin Graft for long-term evaluations, compared to the active comparator, OsteoBiol-Gen-Os® graft, as a treatment for alveolar ridge preservation following tooth extraction.

Long term follow-up: from completion of visit 5 (implant placement) up to 5 years from bone grafting per subject (visits 6-9).

Study design: A prospective, randomized, semi double-blinded with blinded assessments clinical investigation, comparing between subjects grafted with Ivory Dentin Graft (Investigational group) and subjects grafted with OsteoBiol-Gen-Os® (comparator group)

Study population: A total of 41 male and female adult subjects between the ages of 18 to 80 years old requiring alveolar ridge preservation that already had mandibular premolar or molar tooth extraction were included to this ongoing study (NCT03150472; short-term follow-up of 4 months following grafting was completed on September 9, 2020). Twenty-three (23) were previously randomized and grafted with Ivory Dentin Graft (Investigational group) and 18 with the active comparator, OsteoBiol Gen-Os (Comparator group). Five (5) subjects early withdrawn the short-term study resulting in 36 subjects included for this long-term study.

Sample size Justification and Statistical Analysis Plan: The rationale for sample size calculation is based on demonstrating non-inferiority in the study primary endpoint between the investigational and the reference comparator groups. The calculations assume a difference of up to 30% (percent as in unit of measure and not of relative difference) woven bone between the treatments, which will be considered equivalent (non-inferiority) and standard deviation of 32%.

Intended Use: bone graft material for the repair or augmentation of bone defects in dental procedures.

Clinical Follow-up: subjects are medically monitored for any long-term side effects (6 and 10 months, 2.5 and 5 years following their grafting procedure) and their dental condition is also followed by dental hygienist.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

prospective, randomized, semi double blinded with blinded assessments study comparing patients grafted with Ivory Dentin Graft (study arm) and patients grafted with OsteoBiol Gen Os (control arm) for alveolar ridge preservation following tooth extraction.

Masking: Double (Participant, Outcomes Assessor)
Masking Description:

Only the graft performing sub-investigator and the study coordinator are un-blinded to subjects allocation - semi double blinded study.

Primary Purpose: Treatment

Condition

• Deficiency of Alveolar Ridge (Disorder)
• Alveolar Bone Grafting
• Mandibular Prosthesis User

Intervention

• Device: Ivory Dentin Graft
  Ivory Dentin Graft is a bone graft material for the repair or augmentation of bone defects in dental procedures. It consists of sterile 300 - 900 μm porous particles or granules of hydroxyapatite and collagen which retain the natural form of the source porcine dentin and protein matrix. (Packed Vial: 1.00 gr; Packed Syringe: 1.0 gr)
• Device: OsteoBiol Gen-Os
  Comparator control device A natural porcine origin cortico-cancellous heterologous bone mix consists of sterile 250 - 1000 μm porous particles of hydroxyapatite and collagen (Packed Vial: 1.0 gr)

Study Arms

• Experimental: Experimental (Intervention)
  Intervention: Device: Ivory Dentin Graft
• Active Comparator: Active Comparator
  Intervention: Device: OsteoBiol Gen-Os

Publications *

• Hansson S, Halldin A. Alveolar ridge resorption after tooth extraction: A consequence of a fundamental principle of bone physiology. J Dent Biomech. 2012;3:1758736012456543. doi: 10.1177/1758736012456543. Epub 2012 Aug 16.
• Horowitz R, Holtzclaw D, Rosen PS. A review on alveolar ridge preservation following tooth extraction. J Evid Based Dent Pract. 2012 Sep;12(3 Suppl):149-60. doi: 10.1016/S1532-3382(12)70029-5.
• Avila-Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: A systematic review and meta-analysis. J Clin Periodontol. 2019 Jun;46 Suppl 21:195-223. doi: 10.1111/jcpe.13057. Erratum In: J Clin Periodontol. 2020 Jan;47(1):129.
• Chrcanovic BR, Albrektsson T, Wennerberg A. Bone Quality and Quantity and Dental Implant Failure: A Systematic Review and Meta-analysis. Int J Prosthodont. 2017 May/June;30(3):219-237. doi: 10.11607/ijp.5142. Epub 2017 Mar 20.
• Herrmann I, Lekholm U, Holm S, Kultje C. Evaluation of patient and implant characteristics as potential prognostic factors for oral implant failures. Int J Oral Maxillofac Implants. 2005 Mar-Apr;20(2):220-30.
• Barone A, Todisco M, Ludovichetti M, Gualini F, Aggstaller H, Torres-Lagares D, Rohrer MD, Prasad HS, Kenealy JN. A prospective, randomized, controlled, multicenter evaluation of extraction socket preservation comparing two bovine xenografts: clinical and histologic outcomes. Int J Periodontics Restorative Dent. 2013 Nov-Dec;33(6):795-802. doi: 10.11607/prd.1690.
• Mahesh L, Venkataraman N, Shukla S, Prasad H, Kotsakis GA. Alveolar ridge preservation with the socket-plug technique utilizing an alloplastic putty bone substitute or a particulate xenograft: a histological pilot study. J Oral Implantol. 2015 Apr;41(2):178-83. doi: 10.1563/AAID-JOI-D-13-00025. Epub 2013 Jun 17.
• Lai VJ, Michalek JE, Liu Q, Mealey BL. Ridge preservation following tooth extraction using bovine xenograft compared with porcine xenograft: A randomized controlled clinical trial. J Periodontol. 2020 Mar;91(3):361-368. doi: 10.1002/JPER.19-0211. Epub 2019 Aug 23.
• Pang C, Ding Y, Zhou H, Qin R, Hou R, Zhang G, Hu K. Alveolar ridge preservation with deproteinized bovine bone graft and collagen membrane and delayed implants. J Craniofac Surg. 2014 Sep;25(5):1698-702. doi: 10.1097/SCS.0000000000000887.
• Jung RE, Sapata VM, Hammerle CHF, Wu H, Hu XL, Lin Y. Combined use of xenogeneic bone substitute material covered with a native bilayer collagen membrane for alveolar ridge preservation: A randomized controlled clinical trial. Clin Oral Implants Res. 2018 May;29(5):522-529. doi: 10.1111/clr.13149. Epub 2018 Apr 1.
• Meloni SM, Tallarico M, Lolli FM, Deledda A, Pisano M, Jovanovic SA. Postextraction socket preservation using epithelial connective tissue graft vs porcine collagen matrix. 1-year results of a randomised controlled trial. Eur J Oral Implantol. 2015 Spring;8(1):39-48.
• Lee JS, Cha JK, Kim CS. Alveolar ridge regeneration of damaged extraction sockets using deproteinized porcine versus bovine bone minerals: A randomized clinical trial. Clin Implant Dent Relat Res. 2018 Oct;20(5):729-737. doi: 10.1111/cid.12628. Epub 2018 Jul 27.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 27, 2021): 41
• Original Actual Enrollment: Same as current
• Estimated Study Completion Date: April 1, 2025
• Estimated Primary Completion Date: January 10, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female patient 18 up to 80 years.
2. Patient requiring at least one implant placement following mandibular pre-molar or molar tooth extraction.

3. Alveolar mandibular ridge (empty socket):

   • Height: not less than 10 mm, from the gingival margin to the mandibular nerve canal - as seen in the screening CT scan.
   • Width: not less than 5 mm, from buccal to lingual cortical plates - as seen in the screening CT scan.
4. Ability to give informed consent for the study by patient or legal guardian.

5. Willingness to undergo 7 follow up visits: 1 week, 1, 4, 6 and 10 months, 2.5 years and 5 years following dental graft implantation, as well as unscheduled sick visits.

   Exclusion Criteria:

6. Pregnancy (all women of childbearing age would be questioned and told by the consenting physician regarding that criteria).
7. Known or suspected hypersensitivity to the constituents of the bone graft material (for example porcine collagen)
8. Pathologies or conditions contraindicating surgery or presenting with active acute or chronic infections excluding periapical granuloma (for example osteomyelitis, sinusitis), uncontrolled diabetes
9. Immunologic disorders or autoimmune pathologies, in particular elderly
10. Serious bone diseases of endocrine aetiology
11. Serious disturbances of bone metabolism
12. Ongoing treatment with gluco- or mineralocorticoids, or with agents affecting calcium metabolism (e.g. calcitonin, bisphosphonates)
13. Irradiation therapy, chemotherapy or immunosuppressive therapy in the last 5 years
14. Malignancies
15. Severe Parafunction (bruxism and clenching)
16. Poor oral hygiene or active periodontitis
17. Heavy tobacco smoking habit (> 10 cigarettes per day)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT04868825
• Other Study ID Numbers: QF-04-09-01P-
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: IPD is not intended to be shared as this will be a single site study. The study will be public at ClinicalTrial.gov

• Current Responsible Party: Ivory Graft Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ivory Graft Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Tal Lavi, PhD; Ivory Graft Ltd.

• PRS Account: Ivory Graft Ltd.
• Verification Date: April 2021