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Radiation RetinopathyPhase 2RRRNCT02222610

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.

A Phase 2 study testing 0.5 mg ranibizumab and Targeted Retinal Photocoagulation (TRP) in people with Radiation Retinopathy, run by Greater Houston Retina Research at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Radiation Retinopathy
What is being tested?
0.5 mg ranibizumab and Targeted Retinal Photocoagulation (TRP)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesUnited States
Study dates
23 Sep 2014to Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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).
Show all 34Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites
  • Texas Retina Associates

    Dallas, Texas, 75231

  • Retina Consultants of Houston/The Medical Center

    Houston, Texas, 77030

  • Retina Consultants of Houston

    Katy, Texas, 77494

  • Retina Consultants of Houston

    The Woodlands, Texas, 77384

Other trials in United States

About this study

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).

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

Read the detailed 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.

Being tested
0.5 mg ranibizumab, Targeted Retinal Photocoagulation (TRP)
Keywords
Radiation Retinopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 0.5 mg ranibizumabDrug

    Also called Lucentis

  • Targeted Retinal Photocoagulation (TRP)Procedure or surgery

    TRP to areas of retinal ischemia

Study groups in NCT02222610
Study groupRoleWhat they receive
Cohort AExperimentalSubject's will receive monthly treatment of an intravitreal injection of 0.5 mg ranibizumab for 48 weeks. Starting at week 52, subject's will enter a treat \& extend regime, if a subject achieves a "dry" macula. For a macula to be considered "dry" persistent or recurrent fluid must be resolved on spectral domain (SD)-optical coherence tomography (OCT). The interval between injections will not exceed 12 weeks. After a subject is extended beyond 4-weeks \& develops recurrent disease activity, the eye is treated \& the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval. The interval between treatments will be reduced by 1-week intervals until a dry macula is again established. Once a dry macula is again achieved, the interval between visits will be extended by 1-week intervals again.
Receives: Drug: 0.5 mg ranibizumab
Cohort BExperimentalSubject's receive monthly treatment of IVT of 0.5 mg ranibizumab for 48 weeks. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia based on 120° or greater wide field angiography. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks \& 24 weeks \& will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia. Starting at week 52, subject's will enter a treat \& extend regime as described in cohort A.
Receives: Drug: 0.5 mg ranibizumab; Procedure: Targeted Retinal Photocoagulation (TRP)
Cohort CExperimentalSubject's will receive 3 consecutive monthly doses of IVT 0.5 mg ranibizumab followed by PRN treatment with 0.5 mg ranibizumab intravitreal injection. 1 week after the initial dose of IVT ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) to areas of peripheral retinal ischemia. After the first session of TRP, subjects will have a repeat wide field angiogram at 12 weeks \& 24 weeks \& will receive additional TRP as needed (PRN) to areas of peripheral retinal ischemia. Starting at week 52, subject's will enter a treat \& extend regime as described in cohort A.
Receives: Drug: 0.5 mg ranibizumab; Procedure: Targeted Retinal Photocoagulation (TRP)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 104 weeks

Secondary outcomes (4)
  1. The Mean Number of Intravitreal Injections Required Per Subject Per Cohort.

    Measured: 104 weeks

  2. Percentage of Subjects With Retinal Hemorrhage at 104 Weeks.

    Measured: 104 weeks

  3. Percentage of Subjects With Intraretinal Exudates on Fundus Examination at Week 104.

    Measured: 104 weeks

  4. 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.

    Measured: 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2014 (estimated)
  2. Study start23 Sep 2014
  3. Primary completionMar 2019
  4. Study completionMar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02222610
Sponsor's protocol ID
ML29236
Acronym
RRR
Status last verified
Mar 2021
First submitted
20 Aug 2014
Last updated
25 Mar 2021
Data monitoring committee
No
Individual data sharing
No

Publications

  • 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. doi: 10.1016/s0161-6420(02)01277-0.

    PubMed 12466159
  • 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. doi: 10.1016/s0161-6420(00)00526-1.

    PubMed 11158813
  • Gunduz 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. doi: 10.1001/archopht.117.5.609.

    PubMed 10326957
  • 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.

    PubMed 23813109
  • Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. No abstract available.

    PubMed 20142553
  • 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.

    PubMed 21277107
  • 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.

    PubMed 21218391
  • 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. doi: 10.1097/IAE.0b013e31806e6042.

    PubMed 17891015
  • 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.

    PubMed 18313522
  • Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. doi: 10.1001/archopht.125.6.751.

    PubMed 17562985
  • 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.

    PubMed 18698298
  • 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. doi: 10.1097/00006982-200510000-00009.

    PubMed 16205566
  • Finger PT, Kurli M. Laser photocoagulation for radiation retinopathy after ophthalmic plaque radiation therapy. Br J Ophthalmol. 2005 Jun;89(6):730-8. doi: 10.1136/bjo.2004.052159.

    PubMed 15923510
  • Kinyoun JL. Long-term visual acuity results of treated and untreated radiation retinopathy (an AOS thesis). Trans Am Ophthalmol Soc. 2008;106:325-35.

    PubMed 19277244
  • 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. doi: 10.1016/S0161-6420(98)98023-X.

    PubMed 9709753

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 0.5 mg ranibizumab and Targeted Retinal Photocoagulation (TRP) in people with Radiation Retinopathy, run by Greater Houston Retina Research at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity at 104 Weeks From Day 0. (time frame: 104 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02222610, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2021.

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