title: Local rhBMP-12 on an Absorbable Collagen Sponge as an Adjuvant Therapy for Rotator Cuff Repair - A Phase 1, Randomized, Standard of Care Control, Multicenter Study: Safety and Feasibility.
abstract: BACKGROUND
  Recombinant human bone morphogenetic protein-12 (rhBMP-12) has been shown to induce tendon and ligament formation in rats and to improve tendon healing; however, the safety and feasibility of implanting rhBMP-12/absorbable collagen sponge (ACS) in humans are not known.
  
  
  OBJECTIVE
  To investigate the safety and feasibility of rhBMP-12 on an ACS as an adjuvant therapy in open rotator cuff repair.
  
  
  METHODS
  Randomized controlled trial; Level of evidence, 2.
  
  
  METHODS
  This study consisted of 20 patients with full-thickness rotator cuff tears. Patients were randomized either to standard of care (SOC) treatment (open rotator cuff repair) or to receive 0.015 mg/mL rhBMP-12/ACS and SOC treatment during their open rotator cuff repair (rhBMP-12/ACS group) at a rate of 1/4 SOC/rhBMP-12/ACS. The feasibility of implanting the product and the safety of the product were evaluated during the 1-year follow-up period. The evaluation involved up to 10 postoperative visits, which included physical examinations, radiographs, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans with an emphasis on heterotopic ossification (HO), pharmacokinetics, immunogenicity, laboratory evaluations, and local and systemic adverse events at specified time points.
  
  
  RESULTS
  Small amounts of HO were seen on follow-up CT scans in 10 of 16 patients in the rhBMP-12/ACS group and in 2 of 3 patients in the SOC group. HO did not increase at 26 weeks and was not associated with any adverse events or unsatisfactory clinical outcomes. Pharmacokinetics demonstrated that circulating levels of rhBMP-12 were not detectable after administration. Five of 16 patients showed a postoperative immunogenic response but did not show any correlating adverse events. Complete healing of the rotator cuff was observed in 14 of 16 patients; 2 of 16 imaging results could not be analyzed because of artifacts in the rhBMP-12 group on MRI scans. In the SOC group, 1 of 4 patients showed a retear at 12 weeks after surgery.
  
  
  CONCLUSIONS
  The use of rhBMP-12/ACS has been shown to be feasible and safe in a concentration of 0.015 mg/mL when used in open rotator cuff repair. Higher dose concentrations of rhBMP-12 should be evaluated in the future to evaluate their safety and potential to increase rotator cuff healing after open surgical repair.
authors.affiliation: Sporthopaedicum Regensburg, Regensburg, Germany greiner@sporthopaedicum.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Greiner
authors.affiliation: Kumamoto University Hospital, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Ide
authors.affiliation: Spaarne Hospital, Hoofddorp/Heemstede, the Netherlands.
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Noort
authors.affiliation: Hiroshima Prefectural Hospital, Hiroshima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mochizuki
authors.affiliation: Pfizer Inc, Andover, Massachusetts, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Pfizer Inc, Andover, Massachusetts, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Marraffino
authors.affiliation: Pfizer Inc, Andover, Massachusetts, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Sridharan
authors.affiliation: Pfizer Inc, Andover, Massachusetts, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Rudicel
authors.affiliation: Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Itoi
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003094:Collagen; D005240:Feasibility Studies; D055412:Growth Differentiation Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009999:Ossification, Heterotopic; D011184:Postoperative Period; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D017006:Rotator Cuff / Q000473:pathology / Q000601:surgery*; D000070636:Rotator Cuff Injuries; D059039:Standard of Care; D015503:Surgical Sponges; D014945:Wound Healing
chemical_list: D019485:Bone Morphogenetic Proteins; C499470:GDF7 protein, human; D055412:Growth Differentiation Factors; D011994:Recombinant Proteins; D003094:Collagen
keywords: feasibility; rhBMP-12; rotator cuff; safety; shoulder