Topics

Treat & Extend Treatment With 0.5mg Ranibizumab vs Monthly Treatment With 0.5mg Ranibizumab

2015-03-31 07:35:29 | BioPortfolio

Summary

TREX is a phase IIIb, multicenter, randomized, controlled clinical study. Subjects will be randomized 1:2 to "monthly" (control arm) or "treat and extend" protocol (comparator arm) respectively. TREX assess the safety, tolerability and efficacy of intravitreal injections (IVT) of 0.5mg ranibizumab given monthly for up to 100 weeks followed by pro re nata (PRN) treatment for 56 weeks compared to a Treat and Extend protocol for 156 weeks in patients with wet age-related macular degeneration (AMD). Subjects treated in a treat and extend protocol receive 3 consecutive IVT 0.5 mg ranibizumab (visits 2, 4 and 5). Starting at week 8, if a subject has achieved a "dry" macula; signs of active exudation have resolved will begin a Treat and Extend protocol (visits lengthened by 2 week intervals every visit a dry macular is maintained). At the beginning of the 104-week endpoint subjects initially randomized to the TREX cohort will transition to PRN re-treatment when there is no exudative disease activity at the 12-week interval.

Description

This trial will compare the results of 2 cohorts, with different treatment intervals, to assess the safety, tolerability and efficacy of IVT of ranibizumab for the treatment of wet AMD. Specifically, this trial will evaluate the ability to reduce the amount of visits and IVT ranibizumab treatments needed all while maintaining an exudation-free macula. Subjects in both cohorts will be followed for a total of 156 weeks.

Cohort A (control arm, monthly, n=20) Subjects will receive monthly treatment of IVT 0.5 mg ranibizumab from Day 0 to week 100. Monthly treatment is defined as every 28 days (±7 days). Dosing should not occur earlier than 21 days after the previous treatment.

Week 104 - Week 156 Starting at week 104 subjects will be seen monthly and treated with IVT ranibizumab pro re nata (PRN) based on pre-defined re-treatment criteria.

Retreatment criteria for PRN phase

Re-treatment will be initiated if any of the following criteria are meet:

- Presence of any abnormal intraretinal or subretinal fluid on high resolution SD-OCT.

- Presence of new intraretinal or subretinal hemorrhage related to AMD on examination.

- 10 letter loss from previous visit, related to active wet AMD in the opinion of the treating investigator

Cohort B (comparator arm, TREX, n=40) Subjects will receive a minimum of 3 consecutive IVT 0.5 mg ranibizumab (visits 2, 4 and 5). Starting at week 8, if a subject has achieved a "dry" macula; signs of active exudation have resolved by both ophthalmic exam and SD-OCT evaluation they will begin a Treat and Extend protocol.

For a macula to be considered "dry" it must meet both the following criteria:

1. Resolution of intraretinal and subretinal fluid

2. Resolution of all subretinal hemorrhage related to active exudative AMD

Resolution of pigment epithelial detachments (PED) is not required for a macula to be considered "dry". Small intraretinal cystic areas observed on SD-OCT are acceptable and the corresponding macula can be considered dry. The criteria for these are specific; see reference images (Appendix D) for examples of acceptable intraretinal cystic spaces. When cysts described in Appendix D are present the macula should be considered dry and should be notated on the SD-OCT interpretation. Also, minimal increased retinal thickening on SD-OCT without definitive intraretinal or subretinal exudative fluid can be observed and the corresponding macula will be considered dry.

Once a "dry" macula is achieved the interval between visits is then lengthened by 2-week increments, at every visit the macula is "dry". IVT ranibizumab will be rendered at every visit, no earlier than 7 days before the target date and no later than 7 days after the target date; the interval between visits is individualized based on each patient's response to treatment. The interval between injections will not exceed 12 weeks

After a subject is extended beyond 4-weeks and develops recurrent exudative disease activity, the eye is treated and the treatment interval for the next visit is reduced by 2 weeks, compared to the previous treatment interval. The interval between treatments will be reduced by 2-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, instead of 2-week intervals.

For example: If recurrent exudative disease activity is detected after an 8-week interval, the eye is treated and the interval for the next visit is reduced to 6 weeks; if the macula is then dry after the 6-week interval, the interval is increased to 7 weeks. If the macula is then dry after the 7-week interval, the interval is increased to 8 weeks, etc.

Once an eye is extended by 1-week intervals, if recurrent exudative disease is detected again, the treatment interval for the next visit is reduced by 1 week, compared to the previous treatment interval, and will continue to be decreased by 1-week intervals until dry or the 4-week interval is reached. Once a dry macula is again established, the most recent interval between treatments is maintained for one additional visit; if the macula remains dry at this time, the interval will then be extended by 1-week increments.

If an eye exhibits recurrent exudative disease activity 3 times at a given interval and is unable to extend beyond that interval, the eye will continue treatment at the next shorter interval for 3 consecutive visits. After these 3 visits, the interval between visits will again be extended by 1-week intervals, while the macula remains "dry". If the eye exhibits recurrent exudative disease activity, the interval will be decreased by 1-week intervals until the macula is again "dry." The eye will then continue treatment at this interval for 3 consecutive visits before extending by 1-week again. This pattern of repeating 3 visits at the same "dry" interval will be repeated each time after the eye becomes "wet" before again attempting another 1-week extension.

Evidence of recurrent exudative activity

Clinical evidence of recurrent exudative disease activity requiring reducing the interval between treatments includes any of the following:

1. Evidence of subretinal or intraretinal fluid on SD-OCT which is not classified as small intraretinal cystic areas unrelated to active exudative AMD (Appendix D) or minimal increased retinal thickening by SD-OCT without definitive intraretinal or subretinal fluid

2. New macular hemorrhage related to active exudative AMD.

3. ETDRS VA loss of 5 letters from the previous measurement due to neovascular AMD disease process with corresponding SD-OCT evidence of fluid in the macula.

4. Increase in CRT of 50 microns due to active exudative AMD.

The isolated presence of a PED, or enlargement of a PED, does not constitute evidence of exudative disease activity.

If an eye has an ETDRS VA decrease of ≥ 4 lines (20 letters) or a subretinal macular hemorrhage of 1DD or larger, at any point during the trial, the subject will subsequently be treated with ranibizumab every 4 weeks.

Week 104 - Week 156 Starting at Week 104 subjects who have achieved a "dry" macula, at the 12 week interval will be seen monthly and treated pro re nata (PRN) based on pre-defined re-treatment criteria. Study visits should be scheduled to occur every 28 (±7) days relative to the date of week 104 visit.

Retreatment criteria for PRN phase

Re-treatment will be initiated if any of the following criteria are met:

- Presence of any abnormal intraretinal or subretinal fluid on high resolution SD- OCT.

- Presence of new intraretinal or subretinal hemorrhage related to AMD on examination.

- 10 letter loss from previous visit, related to active wet AMD in the opinion of thetreating investigator

Starting at Week 104, subjects who have NOT achieved extension to the 12-week treatment interval will continue with the treat and extend protocol. At any time during weeks 104 to 156 if a subject achieves a "dry" macula, at the 12-week interval, they will immediately begin monthly PRN treatment based on pre-defined re-treatment criteria. Study visits should be scheduled to occur every 28 (±7) days, relative to the date the 12-week interval is achieved. Subjects will not be treated at the visit they achieve the 12 week interval (this is the date PRN treatment will begin).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Macular Degeneration

Intervention

0.5mg ranibizumab

Location

Palmetto Retina Center
West Columbia
South Carolina
United States
29169

Status

Active, not recruiting

Source

Greater Houston Retina Research

Results (where available)

View Results

Links

Published on BioPortfolio: 2015-03-31T07:35:29-0400

Clinical Trials [1027 Associated Clinical Trials listed on BioPortfolio]

A Study of Ranibizumab Administered Monthly or on an As-Needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration

This is a Phase III, multicenter, randomized, double-masked, dose-comparison study of the efficacy and safety of ranibizumab injection administered intravitreally to patients with CNV seco...

The Ranibizumab Plus Transpupillary Thermotherapy for Neovascular Age-Related Macular Degeneration (AMD) Study

Neovascular age-related macular degeneration (AMD) is the leading cause of severe vision loss in the Western world. Intravitreal ranibizumab has recently become the treatment of choice for...

Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

This study will evaluate the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity compared to ranibizumab monotherapy and the durability of ...

Changes in Retinal Function After Intravitreal Ranibizumab for Age-Related Macular Degeneration

Age-related macular degeneration, a leading cause of blindness, is caused by an abnormal growth of the vessels beneath the retina. Ranibizumab (Lucentis) is a new drug that inhibits the gr...

SUSTAIN - Study of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

Ranibizumab is a humanised recombinant monoclonal antibody fragment targeted against human vascular endothelial growth factor A. This study will assess the safety and efficacy of ranibizu...

PubMed Articles [1126 Associated PubMed Articles listed on BioPortfolio]

Safety and tolerability of ranibizumab in uni/bilateral neovascular age-related macular degeneration: 12-month TWEYEs study.

To evaluate the safety and tolerability of ranibizumab 0.5 mg in patients with uni/bilateral neovascular age-related macular degeneration (nAMD) and best-corrected visual acuity (BCVA)

The Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration: Results from the Randomized Phase 2 Ladder Clinical Trial.

To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment.

Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ...

Omega-3 and ranibizumab for age-related macular degeneration: A systematic review protocol.

Omega-3 and ranibizumab (O3R) has been reported to treat age-related macular degeneration (ARMD) effectively. However, up to the present, no systematic review specifically addressed the efficacy of O3...

Canadian Treat and Extend Analysis Trial with Ranibizumab in Patients with Neovascular Age-related Macular Disease: 1-Year Results of the Randomized CANTREAT Study.

To compare the efficacy of ranibizumab using a treat-and-extend (T&E) regimen to monthly dosing in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

Medical and Biotech [MESH] Definitions

A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.

A recombinant humanized monoclonal antibody fragment that binds VEGF-A to prevent its binding to VEGFR-1 and VEGFR-2 receptors. This activity reduces vessel permeability and angiogenesis in the treatment of neovascular age-related MACULAR DEGENERATION.

A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)

Specialized ophthalmic technique used in the surgical repair and or treatment of disorders that include retinal tears or detachment; MACULAR HOLES; hereditary retinal disease; AIDS-related retinal infections; ocular tumors; MACULAR DEGENERATION; DIABETIC RETINOPATHY; and UVEITIS.

A form of RETINAL DEGENERATION in which abnormal CHOROIDAL NEOVASCULARIZATION occurs under the RETINA and MACULA LUTEA, causing bleeding and leaking of fluid. This leads to bulging and or lifting of the macula and the distortion or destruction of central vision.

More From BioPortfolio on "Treat & Extend Treatment With 0.5mg Ranibizumab vs Monthly Treatment With 0.5mg Ranibizumab"

Quick Search

Relevant Topic

Ophthalmology
Ophthalmology is the branch of medicine that is devoted to the study and treatment of eye diseases. As well as mild visual defects correctable by lenses, ophthalmology is concerned with glaucoma, uveitis and other serious conditions affecting the eye, ...


Searches Linking to this Trial