Clinical trial NCT06033703: Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients with Retinal Detachment
Official title: Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients with Primary Rhegmatogenous Detachments and Retinal Detachment Due to Proliferative Vitreoretinopathy or Open-Globe Injury: a Phase I/II Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Rhegmatogenous Retinal Detachment
Proliferative Vitreoretinopathy
Keywords: Vitrectomy
Netarsudil
Pharmacokinetics
Safety
Efficacy
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
First posted: 2023-09-13
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: PREVENTION

Brief summary: This study has two main objectives. The first objective is to study the pharmacokinetics of topical netarsudil administration in the posterior segment of the eye, where netarsudil must exert its effect in order to prevent formation of tractional membranes.

The second objective is to assess the safety profile of topical netarsudil in the pre- and post-operative periods. A secondary objective of the study is to begin to assess signs of efficacy in preventing formation of tractional membranes post-operatively.

Detailed description: This is an open-label, randomized study that will test the safety and pharmacokinetics of topical netarsudil at a dose frequency of once-daily in two cohorts of patients: those with primary rhegmatogenous detachments, and those with established proliferative vitreoretinopathy. The intervention will be topical application of Netarsudil from time of diagnosis of retinal detachment to 16 weeks post-operatively.

Patients will be randomized to one of the following groups:

* The primary rhegmatogenous detachment cohort: A total of 24 study subjects (24 eyes) will be stratified by their lens status (12 phakic versus 12 pseudophakic). All patients will receive once per day dosing of netarsudil.
* The proliferative vitreoretinopathy cohort: A total of 24 study subjects (24 eyes) will be stratified by their lens status (12 phakic versus 12 pseudophakic). All patients will receive once per day dosing of netarsudil.

After surgery, patients will continue on either once per day dosing of Netarsudil.

Eligibility criteria: The primary rhegmatogenous detachment cohort will have the following selection criteria:

Inclusion criteria:

* Patients \> 18 years old
* Patients presenting for primary rhegmatogenous retinal detachment repair within 7 days of symptom onset
* Patients undergoing vitrectomy or vitrectomy with scleral buckle

Exclusion criteria:

* Patient unable to give consent
* Patient unable to follow-up
* Prior history of retinal detachment incisional surgery in presenting eye
* Prior history of open globe injury to presenting eye
* Prior history of glaucoma surgery to presenting eye I.e., Status post trabeculectomy, Ahmed tube placement, minimally invasive glaucoma surgery, actively on glaucoma medication
* Prior history of corneal disease, or history of corneal edema
* Patient already on topical netarsudil in presenting eye
* Patient without natural lens or intraocular lens implant (I.e., aphakic patients)
* Patients with intraocular pressure \<8mm Hg in operative eye
* Active or chronic or recurrent uncontrolled ocular or systemic disease
* Active or history of chronic or recurrent inflammatory eye disease
* Diagnosis of proliferative diabetic retinopathy
* Signs of ocular infection at presentation in either eye
* Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
* Inability to use/ apply topical eye drops

The proliferative vitreoretinopathy cohort will have the following selection criteria:

Inclusion criteria:

* Patients \> 18 years old
* Patient presenting with retinal detachment due with proliferative vitreoretinopathy (grade C or higher) or retinal detachment associated with open globe trauma
* Patients undergoing vitrectomy or vitrectomy with scleral buckle

Exclusion criteria:

* Patient unable to give consent
* Patient unable to follow-up
* Prior history of glaucoma surgery to presenting eye I.e., Status post trabeculectomy, Ahmed tube placement, minimally invasive glaucoma surgery
* Patient already on topical netarsudil in presenting eye
* Patients with intraocular pressure \<8mm Hg in operative eye
* Active or chronic or recurrent uncontrolled ocular or systemic disease
* Active or history of chronic or recurrent inflammatory eye disease
* Diagnosis of severe nonproliferative or proliferative diabetic retinopathy or vasoproliferative disease in operative eye
* Signs of ocular infection at presentation in either eye
* Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
* Inability to use/ apply topical eye drops
* No Light Perception vision in operative eye
* Failure to achieve intraoperative reattachment
* Patient with silicone oil instilled in operative eye at time of presentation

Primary outcomes:
measure: The concentration of netarsudil in the vitreous to assess its pharmacokinetic properties.
timeFrame: Through study completion, an average of 1 year
measure: Serious adverse events
timeFrame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery
Secondary outcomes:
measure: Number of operations within 3 months
timeFrame: Day 84 after surgery
measure: Final attachment status at last follow-up
timeFrame: Day 168 after surgery
measure: Visual acuity
timeFrame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery
measure: Spectral domain optical coherence tomography (SD-OCT) of the macula
timeFrame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery
measure: Adverse events
timeFrame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Massachusetts Eye and Ear
name: Leo Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin CW, Sherman B, Moore LA, Laethem CL, Lu DW, Pattabiraman PP, Rao PV, deLong MA, Kopczynski CC. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma. J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):40-51. doi: 10.1089/jop.2017.0023. Epub 2017 Jun 13.
citation: Singh IP, Fechtner RD, Myers JS, Kim T, Usner DW, McKee H, Sheng H, Lewis RA, Heah T, Kopczynski CC. Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic Solution 0.02% in Patients With Open-angle Glaucoma or Ocular Hypertension. J Glaucoma. 2020 Oct;29(10):878-884. doi: 10.1097/IJG.0000000000001634.
citation: Davies E, Jurkunas U, Pineda R 2nd. Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy. Cornea. 2021 Jul 1;40(7):899-902. doi: 10.1097/ICO.0000000000002691.
citation: Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, Ramirez-Davis N, Kopczynski CC, Usner DW, Novack GD; ROCKET-2 Study Group. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am J Ophthalmol. 2019 Apr;200:130-137. doi: 10.1016/j.ajo.2019.01.003. Epub 2019 Jan 15.
citation: Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack GD, Kopczynski CC; ROCKET-1 and ROCKET-2 Study Groups. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1.
citation: Fernandez MM. Reticular Epithelial Edema in Edematous Corneas Treated with Netarsudil. Ophthalmology. 2018 Nov;125(11):1709. doi: 10.1016/j.ophtha.2018.08.004. No abstract available.
citation: Wisely CE, Liu KC, Gupta D, Carlson AN, Asrani SG, Kim T. Reticular Bullous Epithelial Edema in Corneas Treated with Netarsudil: A Case Series. Am J Ophthalmol. 2020 Sep;217:20-26. doi: 10.1016/j.ajo.2020.04.002. Epub 2020 Apr 11.
citation: LoBue SA, Moustafa GA, Vu A, Amin M, Nguyen T, Goyal H. Transient Reticular Cystic Corneal Epithelial Edema With Topical Netarsudil: A Case Series and Review. Cornea. 2021 Aug 1;40(8):1048-1054. doi: 10.1097/ICO.0000000000002621.