June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
A Phase 1 Safety Study of an Orally Available Tyrosine Kinase Inhibitor X-82 in Previously Treated Wet AMD Patients
Author Affiliations & Notes
  • Philip J Rosenfeld
    Bascom Palmer Eye Institute, Univ of Miami Miller Sch of Med, Miami, FL
  • Jason S Slakter
    Digital Angiographic Reading Center, New York, NY
  • David S Boyer
    Retina-Vitreous Associates Medical Group, Beverly Hills, CA, CA
  • David M Brown
    Retina Consultants of Houston, Houston, TX
  • Nauman A Chaudhry
    New England Retina Associates, Guilford, CT
  • Michael J Elman
    Elman Retina Group, Baltimore, MD
  • Sunil S Patel
    Retina Research Institute of Texas, Abilene, TX
  • Denis O’Shaughnessy
    Xcovery Vision Inc, West Palm Beach, FL
  • Footnotes
    Commercial Relationships Philip Rosenfeld, Xcovery Vision Inc. (C); Jason Slakter, Xcovery Vision (F), Xcovery Vision Inc. (C); David Boyer, Xcovery Vision Inc. (F); David Brown, Xcovery Vision Inc. (F); Nauman Chaudhry, Xcovery Vision Inc. (F); Michael Elman, Xcovery Vision Inc. (F); Sunil Patel, Xcovery Vision Inc. (F); Denis O’Shaughnessy, Xcovery Vision Inc. (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4804. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Philip J Rosenfeld, Jason S Slakter, David S Boyer, David M Brown, Nauman A Chaudhry, Michael J Elman, Sunil S Patel, Denis O’Shaughnessy; A Phase 1 Safety Study of an Orally Available Tyrosine Kinase Inhibitor X-82 in Previously Treated Wet AMD Patients. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4804.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: A phase 1 dose-escalation study to investigate the safety of systemic administration of X-82, an orally active tyrosine kinase inhibitor with activity against all PDGF and all VEGF subtypes.

Methods: Thirty five previously treated subjects with wet AMD were enrolled and received X-82 for up to 6 months at the following doses: 50 mg qod (3 subjects), 50 mg qd (8 subjects), 100 mg qod (4 subjects), 100 mg qd (10 subjects), 200 mg qd (7 subjects) and 200 mg qd (3 subjects). Subjects were seen every 4 weeks and underwent ETDRS VA measurement and SD-OCT assessment to determine the need for ranibizumab rescue therapy at each visit. SD-OCT images were read by DARC, which acted as the independent reading center (IRC).

Results: Twenty-seven of the 35 randomized subjects completed the full 24-week treatment period and 2 subjects are still ongoing. The remaining 6 subjects either withdrew consent or discontinued the study before reaching the 24-week study period. The majority of all patients maintained or improved their baseline visual acuity scores and 24 of the 27 subjects (89%), who completed the 24 week treatment period, did not require any rescue therapy with ranibizumab during the treatment period. Eight subjects (1 who received 100 mg, 5 who received 200 mg and 2 who received 300 mg) experienced significant reductions in fluid on SD-OCT within the first weeks of starting X-82, and these observations were confirmed by the Independent Reading Center (DARC, NY). Three subjects experienced transaminase elevations within the first month of starting therapy, and these parameters returned to normal when X-82 was discontinued. There was no dose relationship in these three cases (1 occurred at 50 mg, 1 at 100 mg and 1 at 200 mg) and none was associated with any other laboratory abnormality or clinical symptoms. One patient on the 300 mg dose discontinued treatment due to grade 2 diarrhea.

Conclusions: The stability of vision without the need for rescue therapy strongly suggests a therapeutic effect for this oral anti-VEGF/PDGF, and the significant reductions in fluid on SD-OCT provide objective support for its activity in previously and frequently treated wet AMD patients. X-82 may offer an alternative way of delivering anti-VEGF and anti-PDGF therapy to patients with wet AMD. Further randomized controlled studies are warranted.

×
×

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.

×