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P. J. Francis, D. G. Birch, J. L. Davis, B. L. Lam, R. Spencer, J. T. Stout, P. Williamson; A Phase 1 Open-Label, Non-Comparative Study Evaluating the Safety of a Single, Unilateral Subretinal Administration of CNTO2476 (Human Umbilical Tissue-Derived Cells [hUTC]) in Advanced Retinitis Pigmentosa (RP). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4789.
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Human umbilical tissue-derived cells (hUTC) have shown efficacy as cell-based therapy in preserving visual function in rodent models of retinal degeneration. The primary objectives of this first-in-human study were to evaluate the preliminary safety and immunogenicity of CNTO 2476, administered subretinally, in subjects with advanced retinitis pigmentosa (RP). Secondary objectives included the preliminary evaluations of changes from baseline in retinal structure and visual function.
Participants with advanced RP (no better than hand-motion vision), after giving informed consent, were enrolled from three US institutions and underwent vitrectomy and single unilateral extramacular subretinal injection of CNTO2476. Evaluations over more than one year of follow up included visual acuity, full-field stimulus thresholds (FFST, Espion Visual Electrophysiology System, Diagnosys LLC), IOP, fundus photography, slit lamp biomicroscopy, and ophthalmoscopy. Retinal structure was assessed by OCT and fluorescein angiography. Systemic evaluations were undertaken to assess evidence of immune rejection.
Seven patients were enrolled (3 men and 4 women), median age was 62 years (range: 41 to 70) and received cell dosages ranging from 47,500 to 470,000 cells delivered transvitreally to the subretinal space through a retinotomy. All patients tolerated the procedure well and no post-operative visual loss was noted. Two patients subsequently developed post-surgical retinal detachments, which appeared related to non-closure of the retinotomy site. There was no clinical evidence of immune rejection. One patient had increased sensitivity and showed repeatable improvement in FFST.
This was a first-in-human study of an allogeneic cellular product that has potential as a treatment for retinal degenerative diseases. Measurement of efficacy was limited by the advanced severity of disease. There was no evidence of immune rejection. Studies are underway to refine the surgical approach. Future studies are planned to determine the efficacy of this therapy in humans.
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