Efficacy and Safety of "Treat-and-Extend" Regimen Versus "Pro Re Nata" of Conbercept in Age-related Macular Degeneration

Age-related Macular Degeneration Clinical Trial

Official title:

A Multicenter Study Comparing Efficacy and Safety of " Treat-and-Extend" Regimen Versus "Pro Re Nata" Regimen of Conbercept in Neovascular Age-related Macular Degeneration

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02802657
• Other study ID #: 15216713049
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 2016
• Est. completion date: September 2020

Study information

• Verified date: May 2020
• Source: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the efficacy and safety of two different regimens of Conbercept (Treat-and-Extend (T&E) Regimen vs. Pro Re Nata (PRN)) in patients with wet AMD. This study is to provide long-term safety data in the treatment of patients with wet Age-related Macular Degeneration (AMD).

Description:

Participants with wAMD were randomized and received a T&E or PRN regimen for 24 months. Mean Snellen BCVA and mean central macular thickness by OCT were examined at each visit. Any treatment-related adverse events, such as endophthalmitis, and systemic adverse events, such as stroke, were evaluated during the research.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 141
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Written informed-consent before any evaluation

• Visual impairment due to active CNV,including predominantly classic CNV,minimally classic CNV,occult CNV with no classic component and PCV.

• 50 years old and older

• Chinese

• For study eye: BCVA between 20/30 and 20/320 on electronic visual acuity texting at the time point of both screening and baseline.

Exclusion Criteria:

• Have Stroke and myocardial infarction within 3 months before screening

• Any active periocular and ocular infection and inflammation (including blepharitis, conjunctivitis, keratitis, scleritis, uveitis, intraocular inflammation) while screening and baseline.

• Uncontrolled glaucoma (under treatment [IOP] = 30 mm Hg or depend on researchers) while screening and baseline

• Neovascularization of iris and neovascular glaucoma while screening and baseline

• Any causes led to choroidal neovascularization except Wet AMD (including ICNV,central serous chorioretinopathy,ocular histoplazmoza and pathologic myopia) while screening and baseline

• With structure injury (including vitreous macular traction,epiretinal membrane involving in central fovea,subretinal fibroplasia,laser scar and central fovea atrophy) within 0.5 optic disc diameter to the central of macula while screening and baseline, which may harm the improvement of vision by treatment according to researchers

• Any systemic anti-VEGF medication(as Avastin) use within 3 months before screening

• Any medication systemic use toxic to lens, retina and optic nerve,including iron amine, chloroquine/chloroquine (Plaquenil ®), tamoxifen, phenothiazine and ethambutol

• For study eye:Used to accept following treatments for wet AMD within 3 months or accept following treatments more than three times before baseline: a)Anti-angiogenesis drugs(pegaptanib (Macugen®),ranibizumab ,bevacizumab(Avastin®),VEGF-Trap,KH902;b)Anecortave acetate corticosteroids;c)Protein kinase C inhibitors,squalamine,siRNA; d)PDT (Visudyne®)treatment,external beam radiotherapy, local laser photocoagulation, vitrectomy, submacular surgery and transpupillary thermotherapy

• Any intraocular surgery(including YAG laser) within 3 months before baseline or predicated within 6 months after baseline

• Intraocular or periocular treatment of corticosteroids within 3 months before baseline

• For follow eye:Any anti-angiogenesis treatment(including anti-VEGF,like Lucentis,Avastin® and KH902 ) within 3 months before baseline

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Macular Degeneration

Intervention

Procedure:
• Treat-and-Extend regimen
For the T&E regimen,investigators recorded patients' data after retreatment by 3 monthly intravitreal injections of Conbercept. Patients were examined 6 weeks after the third injection, with ETDRS visual acuity testing, fundus ophthalmoscopy and photography, and OCT, and treated on the same day. The interval between treatments was extended by 2-week (12-week was a maximum) provided that OCT and fundus examination did not show either exudative manifestations or new macular hemorrhage or active CNV or reduced by 2 weeks (4-week was minimum) in case of such manifestations or hemorrhage. The persistence of pigment epithelium detachment was not considered a condition that justified shortening the interval between injections.
• Pro Re Nata
For the PRN group, investigators recorded patients'data after retreatment by 3 monthly intravitreal injections of Conbercept.Subsequent reinjections were given as needed according to the changes in patients'visual acuity and/or the exudation shown by OCT. Four to five weeks after the third and last injection, all patients in the PRN group underwent an examination, including ETDRS visual acuity, fundus photography,and OCT. In case of persistent subfoveal or perifoveal fluid, macular intraretinal edema, visual loss of >5 letters, or the occurrence of a new hemorrhage, patients were retreated. The persistence of hemorrhage without evidence of fluid was not considered a criterion for retreatment. In the absence of retreatment criteria, no further injections were given and another examination was proposed usually 4 weeks later.

Drug:
• Conbercept

Locations

Country	Name	City	State
China	Eye & Ent Hospital of Fudan University	Shanghai
China	Shanghai First People's Hospital	Shanghai
China	Shanghai Tongji Hospital, Tongji University School of Medicine	Shanghai
China	Shanghai Zhongshan Hospital	Shanghai
China	Central Theater Command General Hospital	Wuhan	Hubei

Sponsors (5)

Lead Sponsor	Collaborator
Xiaodong Sun	Central Theater Command General Hospital, Eye & ENT Hospital of Fudan University, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Abedi F, Wickremasinghe S, Islam AF, Inglis KM, Guymer RH. Anti-VEGF treatment in neovascular age-related macular degeneration: a treat-and-extend protocol over 2 years. Retina. 2014 Aug;34(8):1531-8. doi: 10.1097/IAE.0000000000000134. — View Citation

Berg K, Hadzalic E, Gjertsen I, Forsaa V, Berger LH, Kinge B, Henschien H, Fossen K, Markovic S, Pedersen TR, Sandvik L, Bragadóttir R. Ranibizumab or Bevacizumab for Neovascular Age-Related Macular Degeneration According to the Lucentis Compared to Avastin Study Treat-and-Extend Protocol: Two-Year Results. Ophthalmology. 2016 Jan;123(1):51-9. doi: 10.1016/j.ophtha.2015.09.018. Epub 2015 Oct 21. — View Citation

Chen YN, Powell AM, Mao A, Sheidow TG. RETROSPECTIVE REVIEW OF LUCENTIS "TREAT AND EXTEND" PATTERNS AND OUTCOMES IN AGE-RELATED MACULAR DEGENERATION. Retina. 2016 Feb;36(2):272-8. doi: 10.1097/IAE.0000000000000691. — View Citation

Chin-Yee D, Eck T, Fowler S, Hardi A, Apte RS. A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol. 2016 Jul;100(7):914-917. doi: 10.1136/bjophthalmol-2015-306987. Epub 2015 Oct 29. Review. — View Citation

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. — View Citation

Homer N, Grewal DS, Mirza RG, Lyon AT, Gill MK. Transitioning to intravitreal aflibercept following a previous treat-and-extend dosing regimen in neovascular age-related macular degeneration: 24-month results. Eye (Lond). 2015 Sep;29(9):1152-5. doi: 10.1038/eye.2015.87. Epub 2015 May 29. — View Citation

Houston SK 3rd, Rayess N, Cohen MN, Ho AC, Regillo CD. INFLUENCE OF VITREOMACULAR INTERFACE ON ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY USING TREAT AND EXTEND TREATMENT PROTOCOL FOR AGE-RELATED MACULAR DEGENERATION (VINTREX). Retina. 2015 Sep;35(9):1757-64. doi: 10.1097/IAE.0000000000000663. — View Citation

Li X, Xu G, Wang Y, Xu X, Liu X, Tang S, Zhang F, Zhang J, Tang L, Wu Q, Luo D, Ke X; AURORA Study Group. Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study. Ophthalmology. 2014 Sep;121(9):1740-7. doi: 10.1016/j.ophtha.2014.03.026. Epub 2014 May 1. — View Citation

Mrejen S, Jung JJ, Chen C, Patel SN, Gallego-Pinazo R, Yannuzzi N, Xu L, Marsiglia M, Boddu S, Freund KB. Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration. J Clin Med. 2015 Jul 8;4(7):1380-402. doi: 10.3390/jcm4071380. — View Citation

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. — View Citation

Rush RB, Simunovic MP, Vandiver L, Aragon AV 2nd, Ysasaga JE. Treat-and-extend bevacizumab for neovascular age-related macular degeneration: the importance of baseline characteristics. Retina. 2014 May;34(5):846-52. doi: 10.1097/IAE.0000000000000033. — View Citation

Spaide R. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol. 2007 Apr;143(4):679-80. — View Citation

Wykoff CC, Croft DE, Brown DM, Wang R, Payne JF, Clark L, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: TREX-AMD 1-Year Results. Ophthalmology. 2015 Dec;122(12):2514-22. doi: 10.1016/j.ophtha.2015.08.009. Epub 2015 Sep 29. — View Citation

Zhang M, Zhang J, Yan M, Luo D, Zhu W, Kaiser PK, Yu DC; KH902 Phase 1 Study Group. A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration. Ophthalmology. 2011 Apr;118(4):672-8. doi: 10.1016/j.ophtha.2010.08.008. Epub 2010 Dec 13. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Snellen BCVA at every visit or treatment	Compare of mean Snellen Best-Corrected-visual-acuity at every visit or treatment between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept.	24 months
Secondary	Number of participants with treatment-related adverse events	Compare of Number of participants with treatment-related adverse events between the two groups to assess the safety of Treat-and-Extend regimen of Conbercept	24 months
Secondary	Mean number of injections after the initial three loading dose monthly injections	Compare of mean number of injections after the initial three loading dose monthly injections between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept.	21 months
Secondary	mean central macular thickness at every visit or treatment by OCT	Compare of mean central macular thickness by OCT at every visit or treatment between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept.	24 months