Suprachoroidal CLS-TA Alone or in Combination With Intravitreal Aflibercept for DME

Diabetic Macular Edema Clinical Trial

— HULK  

Official title:

Open-Label Study of the Safety and Efficacy of Suprachoroidal CLS-TA Alone or in Combination With Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema (the HULK Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02944240
• Other study ID #: CLS1004-101
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: October 24, 2016
• Last updated: October 24, 2016
• Start date: November 2016

Study information

• Verified date: October 2016
• Source: Greater Houston Retina Research
• Contact: Cassie Cone, BA
• Phone: 713-524-3434
• Email: cassandra.cone[@]houstonretina.com
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To demonstrate the safety and tolerability of suprachoroidal CLS-TA alone or in combination with intravitreal aflibercept in subjects with diabetic macular edema associated with diabetes mellitus.

Description:

The purpose of this trial is to evaluate the safety and preliminary efficacy of suprachoroidal (SC) CLS-TA in subjects with DME associated with diabetes mellitus.

CLS-TA, triamcinolone acetonide injectable suspension, is a sterile, preservative-free, aqueous suspension formulated for administration into the eye. The drug product is terminally sterilized and is intended for single use. CLS-TA is supplied as a 40 mg/mL sterile suspension in a 2 mL/13 mm TopLyo single use vial with a rubber stopper and an aluminum seal.

This is a Phase 1/2, multicenter, open-label study in subjects with DME associated with diabetes mellitus. Subjects will be screened and if eligible, will be assigned to a study arm at the Baseline Visit. Following the Baseline Visit, subjects will participate in six monthly follow-up visits for safety and efficacy assessments and to determine whether additional therapy is needed based upon established criteria.

Subjects will be assigned to one of two treatment arms in the study based upon prior treatment for DME in the study eye. Those subjects who have never received treatment in the study eye for DME or whose DME treatment in the study was more than 1 year prior to the screening date, at the PI's discretion, will be enrolled into the TX Naive study arm. Those subjects who have received treatment for DME in the study eye within the last 12 months, will be enrolled into the Previous TX study arm.

Treatment in the TX Naive arm will consist of one unilateral injections of IVT aflibercept in combination with one unilateral injection of SC CLS-TA in the same eye.

Treatment in the Previous TX arm of the study will consist of one unilateral injection of SC CLS-TA.

Approximately 20 subjects will be assigned in a 1:1 ratio where approximately 10 subjects will be enrolled into the TX Naive arm and approximately 10 subjects will be enrolled into the Previous TX arm.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men or women = 18 years of age with type 1 or type 2 diabetes mellitus

• DME with central involvement (= 320 microns in the central subfield on SD-OCT) in the study eye

• ETDRS BCVA letter score of 83 to 14, inclusive (Snellen equivalent of 20/25 to 20/500) in the study eye

• Understands the language of the informed consent; willing and able to provide written informed consent prior to any study procedures; willing to comply with the instructions and attend all scheduled study visits

Exclusion Criteria:

• Evidence of DME due to any cause other than diabetes mellitus in the study eye

• Panretinal photocoagulation or focal laser photocoagulation in the study eye within 90 days of screening

• Intraocular pressure = 22 mmHg or uncontrolled glaucoma (open angle or angle closure) in the study eye

• History of any previous ophthalmic surgeries in the study eye within 90 days of screening

• High Risk Proliferative Diabetic Retinopathy in the study eye, for whom enrollment into the study, in the principal investigator's opinion would put the eye at undue risk for vision loss

• Any previous treatment in the study eye with ILUVIEN implant

• Previous treatment for DME in the study eye (TX Naive arm only); treatment in the study eye for DME greater than 1 year prior to screening can be considered as treatment naive at the principal investigator's discretion

• Subjects previously treated for DME cannot have been treated in the study eye with an intravitreal injection of anti-VEGF or periocular corticosteroids within 90 days prior to screening (Previous TX arm only)

• Subjects previously treated for DME can not have been treated in the study eye with intraocular corticosteroids within 6 months prior to screening (Previous TX arm only)

• Known hypersensitivity to any component of the CLS-TA, fluorescein, or topical anesthetic

• Uncontrolled blood pressure (defined as = 180/110 mmHg systolic/diastolic, while seated)

• If female, the subject must be non-pregnant, non-lactating and not planning a pregnancy. Females of childbearing potential must agree to use an acceptable method of contraception throughout participation in this study. Acceptable methods of contraception include double barrier methods (condom with spermicide or diaphragm with spermicide), hormonal methods (oral contraceptives, implantable, transdermal, or injectable contraceptives), or an intrauterine contraceptive device with a documented failure rate of less than 1% per year. Abstinence may be considered an acceptable method of contraception at the discretion of the investigator, but the subject must agree to use one of the acceptable birth control methods if she becomes sexually active

• Currently enrolled in an investigational drug or device study or has used an investigational drug or device within the last 30 days

Study Design

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

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• SC CLS-TA
Suprachoroidal injection of triamcinolone acetonide injectable solution [4 mg (100 µL)]
• IVT Aflibercept
Intravitreal injection of aflibercept [2 mg (50 µL)]

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Greater Houston Retina Research	Clearside Biomedical, Inc.

References & Publications (15)

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Bourne RR, Jonas JB, Flaxman SR, Keeffe J, Leasher J, Naidoo K, Parodi MB, Pesudovs K, Price H, White RA, Wong TY, Resnikoff S, Taylor HR; Vision Loss Expert Group of the Global Burden of Disease Study. Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe: 1990-2010. Br J Ophthalmol. 2014 May;98(5):629-38. doi: 10.1136/bjophthalmol-2013-304033. Epub 2014 Mar 24. Review. — View Citation

Boyer DS, Yoon YH, Belfort R Jr, Bandello F, Maturi RK, Augustin AJ, Li XY, Cui H, Hashad Y, Whitcup SM; Ozurdex MEAD Study Group. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014 Oct;121(10):1904-14. doi: 10.1016/j.ophtha.2014.04.024. Epub 2014 Jun 4. — View Citation

Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, Heier JS, Terasaki H, Kaiser PK, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Korobelnik JF. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52. doi: 10.1016/j.ophtha.2015.06.017. Epub 2015 Jul 18. — View Citation

Campochiaro PA, Brown DM, Pearson A, Chen S, Boyer D, Ruiz-Moreno J, Garretson B, Gupta A, Hariprasad SM, Bailey C, Reichel E, Soubrane G, Kapik B, Billman K, Kane FE, Green K; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012 Oct;119(10):2125-32. doi: 10.1016/j.ophtha.2012.04.030. Epub 2012 Jun 21. — View Citation

Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18. — View Citation

Diabetic Retinopathy Clinical Research Network., Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. — View Citation

Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033. — View Citation

Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. — View Citation

Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012. JAMA. 2015 Sep 8;314(10):1021-9. doi: 10.1001/jama.2015.10029. — View Citation

Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031. — View Citation

Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11. — View Citation

Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806. — View Citation

Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv Ophthalmol. 2012 Jul-Aug;57(4):347-70. doi: 10.1016/j.survophthal.2012.01.004. Epub 2012 Apr 28. Review. — View Citation

Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, Brucker AJ, Ferris FL, Hampton GR, Jhaveri C, Melia M, Beck RW; Diabetic Retinopathy Clinical Research Network.. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAE) and serious adverse events (SAEs)	Incidence of treatment-emergent adverse events (TEAE) and serious adverse events (SAEs), grouped by organ system, relatedness to study treatment and severity.	6 months	Yes
Primary	Mean change in intraocular pressure	Mean change from baseline in intraocular pressure at each follow-up visit	6 months	Yes
Secondary	Mean change in central subfield thickness	Mean change from baseline in central subfield thickness at each follow-up visit	6 months	No
Secondary	Mean change in ETDRS BCVA	Mean change from baseline in Early Treatment Diabetic Retinopathy Study Best-Corrected Visual Acuity at each follow-up visit.	6 months	No
Secondary	Mean number of suprachoroidal CLS-TA administered	Mean number of suprachoroidal injections of CLS-TA administered over 6 months	6 months	No