A Safety and Efficacy Trial of a Treat and Extend Protocol Using Ranibizumab With and Without Laser Photocoagulation for Diabetic Macular Edema

NCT01934556 | Completed Phase 1 Results

• 1 other identifier: ML28724
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to determine if a "Treat and Extend" regimen (increasing the time between visits when the disease is stable and not getting worse) of Ranibizumab 0.3 mg injections inside the eye is safe and effective at treating patients with swelling of the retina from diabetes.

Conditions

Diabetic Macular Edema

Outcome Measures

Primary Outcomes (1)

• Mean Change in Vision at 24 Months

  Mean change in ETDRS (Early Treatment in Diabetic Retinopathy Study) visual acuity at 24 months (week 92-week 107) from Day 0. Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard. A higher letter score represents better functioning"

  2 Years

Secondary Outcomes (8)

• Number of Participants With Adverse Events

  2 years

• Number of Intravitreal Injections

  2 years

• Number of Office Visits

  2 years

• Change in Retinal Thickness

  2 years

• Percentage of Eyes Gaining or Losing Vision

  2 years

Study Arms (3)

Monthly

ACTIVE COMPARATOR

Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.

Drug: Ranibizumab 0.3 mg intravitreal injection

TREX

ACTIVE COMPARATOR

(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.

Drug: Ranibizumab 0.3 mg intravitreal injection

GILA

ACTIVE COMPARATOR

(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.

Drug: Ranibizumab 0.3 mg intravitreal injection; Device: Guided Laser Photocoagulation

Interventions

Ranibizumab 0.3 mg intravitreal injection DRUG

Also known as: Ranibizumab, Lucentis

GILA; Monthly; TREX

Guided Laser Photocoagulation DEVICE

Also known as: NAVILAS Guided Laser System

GILA

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age \> 18 years of age Patient related considerations
• For sexually active women of childbearing potential, agreement to the use of an appropriate form of contraception (or abstinence) for the duration of the study
• Although no birth control method is 100% effective, the following are considered effective means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception using either a condom or diaphragm with spermicidal gel, an intrauterine device, or contraceptive hormone implant or patch. A patient's primary care physician, obstetrician, or gynecologist should be consulted regarding an appropriate form of birth control.
• Ability and willingness to return for all scheduled visits and assessments
• Disease related considerations
• The presence of center-involving diabetic macular edema on clinical exam and SDOCT
• Best corrected visual acuity in the study eye, using ETDRS testing, between 20/25 and 20/320 (Snellen equivalent), inclusive.
• Clear ocular media and adequate pupillary dilation to permit good quality fundus imaging.

You may not qualify if:

• Pregnancy (positive urine pregnancy test) or lactation.
• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD (Intrauterine Device) , 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 another simultaneous medical investigation or trial
• History of active proliferative diabetic retinopathy in the study eye on clinical exam
• History of vitrectomy surgery, submacular surgery, or other intraocular surgical intervention for diabetic macular edema in the study eye
• Any previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection, anti-VEGF drugs including ranibizumab, or device implantation) in the study eye within 90 days of the screening visit.
• Evidence of vitreomacular interface abnormality or epiretinal membranes which may be responsible for macular edema
• Concurrent Ocular Conditions
• Any concurrent intraocular condition in the study eye (e.g., cataract or macular degeneration) that, in the opinion of the investigator, could either: Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition; or if allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of BCVA (Best Corrected Visual Acuity) over the 24-month study period.
• Active intraocular inflammation (grade trace 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

Sponsors & Collaborators

• Palmetto Retina Center, LLC: lead

Study Sites (3)

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Retina Consultants of Houston

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Payne JF, Wykoff CC, Clark WL, Bruce BB, Boyer DS, Brown DM; TREX-DME Study Group. Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results. Br J Ophthalmol. 2021 Feb;105(2):253-257. doi: 10.1136/bjophthalmol-2020-316176. Epub 2020 Apr 17.

  PMID: 32303499 DERIVED

• Payne JF, Clark WL, Bruce BB, Wykoff CC, Brown DM, Menke BM, Iverson SM, Allen KF, Boyer DS; Treat & Extend Protocol in Patients with Diabetic Macular Edema Study Group. Retinopathy Regression with Treat and Extend Ranibizumab for Diabetic Macular Edema. Ophthalmology. 2018 Aug;125(8):1304-1306. doi: 10.1016/j.ophtha.2018.03.046. Epub 2018 May 3. No abstract available.

  PMID: 29729809 DERIVED

• Payne JF, Wykoff CC, Clark WL, Bruce BB, Boyer DS, Brown DM; TREX-DME Study Group. Randomized Trial of Treat and Extend Ranibizumab with and without Navigated Laser for Diabetic Macular Edema: TREX-DME 1 Year Outcomes. Ophthalmology. 2017 Jan;124(1):74-81. doi: 10.1016/j.ophtha.2016.09.021. Epub 2016 Nov 8.

  PMID: 27836430 DERIVED

MeSH Terms

Interventions

Ranibizumab; Intravitreal Injections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Injections, Intraocular; Injections; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: John F. Payne, MD
• Organization: Palmetto Retina Center, LLC

jpayne@palmettoretina.com

(803) 931-0077

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2013
• First Posted: September 4, 2013
• Study Start: November 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2018
• Last Updated: November 17, 2020
• Results First Posted: November 17, 2020

Record last verified: 2020-10

Locations

US (3)