Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation to Treat Radiation Retinopathy.

Radiation Retinopathy Clinical Trial

— RRR  

Official title:

A Randomized, Active-Controlled, Phase II Study of the Efficacy and Tolerability of Intravitreal Injections of Ranibizumab Compared to Intravitreal Injections of Ranibizumab Combined With Targeted Retinal Photocoagulation in Subjects With Radiation Retinopathy (RRR Study).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02222610
• Other study ID #: ML29236
• Status: Completed
• Phase: Phase 2
• Start date: September 23, 2014
• Est. completion date: March 2019

Study information

• Verified date: March 2021
• Source: Greater Houston Retina Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the tolerability and efficacy of ranibizumab treatment administered in subjects with radiation retinopathy

Description:

RRR is a phase II, randomized, multicenter, clinical study to assess the tolerability and efficacy of ranibizumab treatment administered in subjects with radiation retinopathy. Subjects will be randomized into one of 3 arms; intravitreal (IVT) monthly vs. ranibizumab treatment administered IVT monthly combined with peripheral targeted photocoagulation vs. ranibizumab treatment administered IVT for three months followed by as needed treatment of ranibizumab combined with peripheral targeted photocoagulation over 48 weeks. From week 52 to week 101, all 3 treatment arms will employ a treat and extend protocol for IVT ranibizumab treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Subjects will be eligible to participate if the following criteria are met:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

• Age > 18 years

• Active radiation retinopathy resulting from any form of radiation treatment performed within the last 3 years. Radiation retinopathy is defined as any of the following: retinal hemorrhages, exudates, edema, and/or neovascularization, not attributable to other causes.

• Best Corrected Visual Acuity (BCVA) of 20/25-20/400 in the study eye

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

• Pregnancy (verified by positive pregnancy test) or lactation

• Premenopausal women not using adequate methods of contraception. The following are considered effective means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch.

• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.

• Participation in any other simultaneous medical investigation or trial

• Previous participation in any studies involving investigational drugs within 30 days before Day 0 (excluding vitamins and minerals).

• History of allergy fluorescein, not amenable to treatment

• Previous intravitreal treatment with any anti-vascular endothelial growth factor (VEGF) drug within 60 days of Day 0

• Previous intravitreal or subconjunctival treatment with cortical steroids within 90 days of Day 0

• History of vitrectomy

• History of treatment with more than one form of radiation to the eye (e.g. proton beam therapy and plaque therapy).

• Subjects who have more than 7 disc diameters of ischemia in the central macula that would hinder visual acuity improvement

• History of panretinal photocoagulation treatment in the study eye.

• Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed

• Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could:

• Require medical or surgical intervention during the 12 month study period to prevent or treat visual loss that might result from that condition.

• Contribute to loss of at least 2 Snellen equivalent lines of BCVA over the 12-month study period, if allowed to progress untreated.

• Active intraocular inflammation (grade 2+ or above) in the study eye

• Current vitreous hemorrhage in the study eye

• History of rhegmatogenous retinal detachment or macular hole (stage 3 or 4) in the study eye.

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

• Aphakia or absence of the posterior capsule in the study eye.

• Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0.

• Uncontrolled glaucoma in the study eye (defined as intraocular pressure (IOP) > 30 mmHg despite treatment with anti-glaucoma medication).

• History of glaucoma-filtering surgery in the study eye

• History of corneal transplant in the study eye

• Uncontrolled blood pressure (defined as systolic and/or diastolic > 180/110 mmHg while subject is seated). If the subject's initial reading exceeds these values, a second reading may be taken at least 30 minutes later. If the subject requires antihypertensive medication, the subject can become eligible if medication is taken continuously for at least 14 days prior to Day 0 and blood pressure is less that 180/110 mmHg.

• New diagnosis of atrial fibrillation not managed by subject's primary care physician or cardiologist within 3 months of Day 0.

• History of stroke within the last 3 months of Day 0.

• History of myocardial infarction within 3 months of Day 0.

• History of other disease, metabolic dysfunction, or physical examination finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or renders the subject at high risk for treatment complications.

• Current treatment for active systemic infection

• Active malignancy other than uveal melanoma

• Presence of metastases

Related Conditions & MeSH terms

• Radiation Retinopathy
• Retinal Diseases

Intervention

Drug:
• 0.5 mg ranibizumab

Procedure:
• Targeted Retinal Photocoagulation (TRP)
TRP to areas of retinal ischemia

Locations

Country	Name	City	State
United States	Texas Retina Associates	Dallas	Texas
United States	Retina Consultants of Houston/The Medical Center	Houston	Texas
United States	Retina Consultants of Houston	Katy	Texas
United States	Retina Consultants of Houston	The Woodlands	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Greater Houston Retina Research	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (20)

Boyer DS, Heier JS, Brown DM, Francom SF, Ianchulev T, Rubio RG. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009 Sep;116(9):1731-9. doi: 10.1016/j.ophtha.2009.05.024. Epub 2009 Jul 29. — View Citation

Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. — View Citation

Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009 Jan;116(1):57-65.e5. doi: 10.1016/j.ophtha.2008.10.018. — View Citation

Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. — View Citation

Finger PT, Chin KJ. Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27. — View Citation

Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28. — View Citation

Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. — View Citation

Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2005 Jun;89(6):730-8. — View Citation

Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011 Jul-Aug;21(4):446-51. doi: 10.5301/EJO.2011.6213. — View Citation

Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):974-7. doi: 10.1016/j.ijrobp.2007.11.045. — View Citation

Gündüz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999 May;117(5):609-14. — View Citation

Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302. — View Citation

Hykin PG, Shields CL, Shields JA, Arevalo JF. The efficacy of focal laser therapy in radiation-induced macular edema. Ophthalmology. 1998 Aug;105(8):1425-9. — View Citation

Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, Diddie KR, Engstrom RE Jr, Finger PT, Hovland KR, Joffe L, Olsen KR, Wells CG; Collaborative Ocular Melanoma Study Group (COMS Group). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology. 2002 Dec;109(12):2197-206. Erratum in: Ophthalmology. 2004 Aug;111(8):1514. — View Citation

Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:325-35. — View Citation

Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS. Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma. Retina. 2007 Sep;27(7):903-7. — View Citation

Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, Hanson WF, Montague P, Moy CS, Schachat AP, Simpson ER, Straatsma BR, Vine AK, Weingeist TA; Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348-66. — View Citation

Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008 Feb;145(2):239-248. doi: 10.1016/j.ajo.2007.10.004. — View Citation

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. — View Citation

Shields CL, Demirci H, Dai V, Marr BP, Mashayekhi A, Materin MA, Manquez ME, Shields JA. Intravitreal triamcinolone acetonide for radiation maculopathy after plaque radiotherapy for choroidal melanoma. Retina. 2005 Oct-Nov;25(7):868-74. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0.	Early Treatment Diabetic Retinopathy Study (ETDRS) Best-Corrected Visual Acuity (BCVA) utilizes the ETDRS visual acuity chart to measure vision in clinical trials. Standard unit of measure is the number of letters subjects are able to read on the chart.	104 weeks
Secondary	The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.		104 weeks
Secondary	Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.		104 weeks
Secondary	Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.		104 weeks
Secondary	Mean Change in Central Mean Thickness According to Spectral-domain Optical Coherence Tomography at Week 104 Compared to Baseline.	Spectral-domain optical coherence tomography (SD-OCT) is a common imaging modality used to visualize the layers of the macula. Central mean thickness (CMT) is the length in microns from the internal limiting membrane to Bruch's membrane.	104 weeks