A PHASE I II CLINICAL-TRIAL TO EVALUATE A COMBINATION OF RECOMBINANT HUMAN PLATELET-DERIVED GROWTH FACTOR-BB AND RECOMBINANT HUMAN INSULIN-LIKE GROWTH-FACTOR-I IN PATIENTS WITH PERIODONTAL-DISEASE/

THE PRIMARY OBJECTIVE OF THIS STUDY was to assess the safety of recomb inant human (rh) platelet-derived growth factor-BE (PDGF-BB) and (rh) insulin-like growth factor-I (IGF-T) when applied to periodontal osseo us defects in humans; a secondary objective was to begin to accrue dat a on the therapeutic dose of these growth factors (GFs) required to st imulate periodontal regeneration. Thirty-eight human subjects possessi ng bilateral osseous periodontal lesions were assigned to one of two t reatment groups in a split-mouth design. Following full-thickness flap reflection, test sites received local application of the therapeutic drug delivered in coded syringes by a ''masked'' investigator. Two dos e levels were tested, 50 mu g/ml each of rhPDGF-BB and rhIGF-I in a ge l vehicle (LD-PDGF/IGF-I) and 150 mu g/ml each of rhPDGF-BB and rhIGF- I plus vehicle (HD-PDGF/IGF-I), Control treatment consisted of either conventional periodontal flap surgery or surgery plus vehicle. Safety analyses included physical examination, hematology, serum chemistry, u rinalysis, antibody titers, and radiographic evaluation of bony change s. The primary therapeutic assessment was bone fill measured at re-ent ry 6 to 9 months after treatment. No local or systemic safety issues w ere found as a result of GF administration. No patients developed anti bodies to the rhGF proteins. In subjects treated with LD-PDGF/IGF-I, t here were no enhancements in periodontal regeneration compared to cont rols. However, in patients treated with HD-PDGF/IGF-I, statistically s ignificant increases in alveolar bone formation were noted as measured by surgical re-entry 9 months following drug delivery (P < 0.05). Thi s corresponded to an increase of 2.08 mm of new vertical bone height a nd 42.3% osseous defect fill in the HD-PDGF/IGF-I subjects versus only 0.75 mm and 18.5% gains in new bone height and osseous fill, respecti vely, in the controls. Furcation lesions, although limited in number, responded most favorably to treatment, with 2.8 mm horizontal osseous fill. The results from this study suggest that the local application o f rhPDGF-BB and rhIGF-I to periodontal lesions is safe at the dose lev els studied. LD-PDGF/IGF-I did not elicit increased defect fill compar ed to the control; however, HD-PDGF/IGF-I resulted in a significant pr omotion in bone regeneration. Additional studies are warranted to more fully characterize the effects of PDGF/IGF-I on periodontal regenerat ion in humans.