June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A Phase 1/2 multidose, dose escalation study to evaluate RXI-109 administered by intravitreal injection to reduce the progression of subretinal fibrosis in subjects with advanced neovascular AMD (NVAMD)
Author Affiliations & Notes
  • Michael Byrne
    RXi Pharmaceuticals, MARLBOROUGH, Massachusetts, United States
  • Natalie Gagne
    Clinical, RXi Pharmaceuticals, Marlborough, Massachusetts, United States
  • Gulnar Hafiz
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Tahreem Mir
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Manasa Survi
    Clinical, RXi Pharmaceuticals, Marlborough, Massachusetts, United States
  • Laurie Barefoot
    Clinical, RXi Pharmaceuticals, Marlborough, Massachusetts, United States
  • James Cardia
    RXi Pharmaceuticals, MARLBOROUGH, Massachusetts, United States
  • Karen Bulock
    RXi Pharmaceuticals, MARLBOROUGH, Massachusetts, United States
  • Pamela A Pavco
    RXi Pharmaceuticals, MARLBOROUGH, Massachusetts, United States
  • Peter A Campochiaro
    Wilmer Eye Institute, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Michael Byrne, RXi Pharmaceuticals (E); Natalie Gagne, RXi Pharmaceuticals (E); Gulnar Hafiz, None; Tahreem Mir, None; Manasa Survi, RXi Pharmaceuticals (E); Laurie Barefoot, RXi Pharmaceuticals (E); James Cardia, RXi Pharmaceuticals (E); Karen Bulock, RXi Pharmaceuticals (E); Pamela Pavco, RXi Pharmaceuticals (E); Peter Campochiaro, Aerpio Therapeutics (F), Aerpio Therapeutics (C), Alimera (F), Alimera (C), Allegro (F), Allegro (C), Allegro (I), Allergan (F), Allergan (C), Applied genetic Technologies (C), AsclipiX (F), AsclipiX (C), Genentech/Roche (F), Genentech/Roche (C), Genzyme (F), Graybug (C), Graybug (I), Interxon (C), Merck (C), Oxford Biomedical (F), Regeneron (F), Regenixbio (C), Regenxbio (F), RXi Pharmaceuticals (F), RXi Pharmaceuticals (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3210. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Michael Byrne, Natalie Gagne, Gulnar Hafiz, Tahreem Mir, Manasa Survi, Laurie Barefoot, James Cardia, Karen Bulock, Pamela A Pavco, Peter A Campochiaro; A Phase 1/2 multidose, dose escalation study to evaluate RXI-109 administered by intravitreal injection to reduce the progression of subretinal fibrosis in subjects with advanced neovascular AMD (NVAMD). Invest. Ophthalmol. Vis. Sci. 2017;58(8):3210.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Almost half of the patients with NVAMD on anti-VEGF therapy develop retinal scars within two years of initiating treatment. These scars have a negative impact on vision. A major contributor to the scarring process is the upregulation of connective tissue growth factor (CTGF). Here we investigate the potential of RXI-109, a self-delivering oligonucleotide (sd-rxRNA®) that works through an RNA interference mechanism to reduce CTGF mRNA levels and decrease CTGF protein levels in patients with NVAMD.

Methods : RXI-109 is being evaluated in a Phase 1/2, multidose, dose escalation study to reduce the progression of subretinal fibrosis in subjects with NVAMD. At least 9 subjects, 3 per dose cohort, will be enrolled. Subjects receive 4 doses of RXI-109 administered monthly by intravitreal injection followed by a four-month observation period. Safety assessments include the incidence, severity and relationship of adverse events (AEs). Pharmacokinetic parameters of RXI-109 in blood will be assessed. Clinical assessments include OCT, color fundus photography, FA, ocular exams and best corrected visual acuity throughout the study. Clinical activity will be determined by comparison of lesion size vs. baseline. Evaluation of CTGF levels in aqueous fluid of treated eyes is planned.

Results : Cohorts 1 (0.1 mg/injection) and 2 (0.3 mg/injection) are fully enrolled. Cohort 3 (0.45 mg/injection) enrollment is ongoing. No serious AEs have been reported. AEs such as conjunctival hyperemia and mild vitreous/sub-conjunctival hemorrhage have been reported and have been judged as not related to study drug.

Conclusions : To date, RXI-109, an sd-rxRNA compound that reduces CTGF mRNA levels has been found to be safe and well tolerated following intravitreal injection in subjects with NVAMD. Safety assessments continue and clinical activity will be evaluated at study’s end. RXI-109 and the sd-rxRNA platform have the potential to fill an unmet medical need to reduce retinal fibrosis subsequent to NVAMD and preserve vision.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×