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

NCT01748292 | Completed Phase 3 Results

• 1 other identifier: ML28513
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Macular Degeneration

Keywords

Age related; Macular; sub retinal fluid; Age related Macular degeneration

Outcome Measures

Primary Outcomes (1)

• Mean Change in BCVA by ETDRS Letter Score From Baseline

  Mean change in Best-Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline through weeks 24-28, baseline through weeks 48-56, baseline through weeks 72-82, baseline to week 104, baseline through weeks 128-132 and baseline to week 156. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning. The scale ranges from 0 to 100 letters

  6, 12, 18, 24, 30, and 36 months

Secondary Outcomes (7)

• Incidence and Severity of Adverse Events (Ocular and Non-ocular)

  36 months

• Total Number of Intravitreal Injections Required

  12, 24, and 36 months

• Total Number of Office Visits and Imaging Studies Performed During Study Period

  6, 12, 18, 24, 30, and 36 months

• Percentage of Subjects With Persistent Active Exudation on SD-OCT

  12, 24, and 36 months

• Mean Change in Central Foveal Thickness

  12, 24, and 36 months

Study Arms (2)

Monthly IVT ranibizumab

ACTIVE COMPARATOR

Monthly intravitreal injections (IVT) ranibizumab for 24 months, not less than 21 days apart to not more than 35 days apart

Drug: 0.5 mg ranibizumab

Treat and Extend IVT ranibizumab

EXPERIMENTAL

0.5 mg intravitreal injections (IVT) ranibizumab for 3 consecutive months followed by a treat and extend protocol in which follow-up intervals are increased when there is no clinical and SD-OCT evidence of disease activity by 2-week intervals and patients are treated at every visit. (Comparator arm)

Drug: 0.5 mg ranibizumab

Interventions

0.5 mg ranibizumab DRUG

Subject will receive drug (ranibizumab) via intravitreal injections (IVT) at every visit.

Also known as: Lucentis

Monthly IVT ranibizumab; Treat and Extend IVT ranibizumab

Eligibility Criteria

• Age: 50 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 \> 50 years
• Ability and willingness to return for all scheduled visits and assessments
• Any CNVM lesion (Occult, Minimally Classic or Classic) (i.e., leakage on fluorescein angiography or subretinal, intraretinal activity on SDOCT) secondary to age-related macular degeneration.
• Best corrected visual acuity in the study eye, using ETDRS testing, between 20/32 and 20/400 (Snellen equivalent), inclusive.
• The total area of subretinal hemorrhage and fibrosis must comprise less than 50% of the total lesion. Clear ocular media and adequate pupillary dilation to permit good quality fundus imaging.

You may not qualify if:

• Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \> 50% of the total area of the lesion or \> 1 disc area (2.54 mm2) in size
• Subfoveal fibrosis or atrophy in the study eye
• CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia

Sponsors & Collaborators

• Charles C Wykoff, PhD, MD: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Retina Consultants of Houston/The Medical Center

Houston, Texas, 77030, United States

Location

Retina Consultants of Houston/Katy office

Katy, Texas, 77494, United States

Location

Retina Consultants of Houston

The Woodlands, Texas, 77384, United States

Location

Related Publications (16)

• 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. doi: 10.1056/NEJMoa062655.

  PMID: 17021319 BACKGROUND

• 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. doi: 10.1056/NEJMoa054481.

  PMID: 17021318 BACKGROUND

• 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.

  PMID: 19643495 BACKGROUND

• 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.

  PMID: 18222192 BACKGROUND

• Schmidt-Erfurth U, Eldem B, Guymer R, Korobelnik JF, Schlingemann RO, Axer-Siegel R, Wiedemann P, Simader C, Gekkieva M, Weichselberger A; EXCITE Study Group. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology. 2011 May;118(5):831-9. doi: 10.1016/j.ophtha.2010.09.004. Epub 2010 Dec 13.

  PMID: 21146229 BACKGROUND

• Busbee BG, Yee W, Li Z, et al. Efficacy and safety of 2.0mg or 0.5mg ranibizumab in patients with subfoveal neovascular AMD: HARBOR Study. American Academy of Ophthalmology; Orlando, Florida October 24, 2011.

  BACKGROUND

• Lalwani GA, Rosenfeld PJ, Fung AE, Dubovy SR, Michels S, Feuer W, Davis JL, Flynn HW Jr, Esquiabro M. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009 Jul;148(1):43-58.e1. doi: 10.1016/j.ajo.2009.01.024. Epub 2009 Apr 18.

  PMID: 19376495 BACKGROUND

• CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011 May 19;364(20):1897-908. doi: 10.1056/NEJMoa1102673. Epub 2011 Apr 28.

  PMID: 21526923 BACKGROUND

• Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group; Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL 3rd. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012 Jul;119(7):1388-98. doi: 10.1016/j.ophtha.2012.03.053. Epub 2012 May 1.

  PMID: 22555112 BACKGROUND

• Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. doi: 10.1056/NEJM199412013312203.

  PMID: 7526212 BACKGROUND

• Spaide R. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol. 2007 Apr;143(4):679-80. doi: 10.1016/j.ajo.2007.02.024. No abstract available.

  PMID: 17386275 BACKGROUND

• Engelbert M, Zweifel SA, Freund KB. "Treat and extend" dosing of intravitreal antivascular endothelial growth factor therapy for type 3 neovascularization/retinal angiomatous proliferation. Retina. 2009 Nov-Dec;29(10):1424-31. doi: 10.1097/IAE.0b013e3181bfbd46.

  PMID: 19898180 BACKGROUND

• Oubraham H, Cohen SY, Samimi S, Marotte D, Bouzaher I, Bonicel P, Fajnkuchen F, Tadayoni R. Inject and extend dosing versus dosing as needed: a comparative retrospective study of ranibizumab in exudative age-related macular degeneration. Retina. 2011 Jan;31(1):26-30. doi: 10.1097/IAE.0b013e3181de5609.

  PMID: 20890246 BACKGROUND

• Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010 Nov;117(11):2134-40. doi: 10.1016/j.ophtha.2010.02.032. Epub 2010 Jul 1.

  PMID: 20591490 BACKGROUND

• Shienbaum G, Gupta OP, Fecarotta C, Patel AH, Kaiser RS, Regillo CD. Bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen: clinical and economic impact. Am J Ophthalmol. 2012 Mar;153(3):468-473.e1. doi: 10.1016/j.ajo.2011.08.011. Epub 2011 Oct 11.

  PMID: 21996309 BACKGROUND

• Wykoff CC, Ou WC, Croft DE, Payne JF, Brown DM, Clark WL, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Neovascular age-related macular degeneration management in the third year: final results from the TREX-AMD randomised trial. Br J Ophthalmol. 2018 Apr;102(4):460-464. doi: 10.1136/bjophthalmol-2017-310822. Epub 2017 Aug 4.

  PMID: 28779006 DERIVED

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The key limitation is the small population analyzed through 3 complete years; subject attrition due to elderly population.

Results Point of Contact

• Title: Charles C. Wykoff, MD, PhD
• Organization: Retina Consultants of Houston

ccwmd@houstonretina.com

713-524-3434

Study Officials

• Charles C Wykoff, PhD, MD

  Retinal Consultants of Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director of Research

Study Record Dates

• First Submitted: December 7, 2012
• First Posted: December 12, 2012
• Study Start: December 1, 2012
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: June 4, 2019
• Results First Posted: October 20, 2017

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)