First in Human Study to Assess Safety and Efficacy of an Implantable Nitinol Device in the Treatment of Keratoconus

Official title

First in Human Study to Assess the Safety and Efficacy of an Implantable Nitinol Device in the Treatment of Stage 3 and 4 Keratoconus

Overview

This Study is a First In Human clinical investigation addressed to evaluate the safety and efficacy of a novel intra-corneal nitinol device (Investigational Medical Device: GROSSO® implant) for the treatment of advanced keratoconus disease of the eye.

Detailed description

The medical device under investigation is a sterile thin 8-mm diameter circular scaffold made of a nickel-titanium alloy (nitinol) that is intended as a permanent implant that is surgically inserted into the cornea in order to modify force by inducing a change in corneal shape and consequently improving vision. This study is aimed at adults with a stage 3- 4 keratoconus, a central K reading \> 47.2 D and RMS of coma aberration \> 2.5 μm, which are not recommended for Intrastromal Corneal Ring Segments (ICRS) and are recommended for keratoplasty. Therefore, this study represents a salvage route to preserve the cornea. Envisaged worst case scenario of failure of the experimental device patients would be redirected to keratoplasty.

Study aims to treat 12 patients separated by a safety period of at least 14 days between each one allowing safety monitoring. For each patient, the following treatment strategy will be applied:

* Unilateral KC: the affected eye meeting the eligibility criteria will be treated. * Bilateral KC, one eye meeting the eligibility criteria: the eligible eye will be treated. * Bilateral KC, both eyes meeting the eligibility criteria: the most severely compromised eye will be treated. Primary study objective is safety by identification or any local or systemic adverse events. Secondary objective will aim to evaluate efficacy that means a consequently improving of vision. Patients will be monitored at 1, 7, 21, 60, 180 and 365 days post implant surgery. Upon observance or any serious adverse event, increase in ocular pressure, device migration or discomfort, medical criteria or patient request, the patient will be offered for the device removed. The study will be early terminated if 3 patients have the experimental device removed for any reason or 4 patients withdraw from study.

Interventions

• Device Nitinol net for intracorneal implant for keratoconus treatment
  The investigational corneal implant device is designed for patients with keratoconus. It is intended to be surgically implanted into the cornea as a permanent implant and is made of nitinol. The device is intended to improve corneal stability and visual outcomes.

Primary outcome measures

• Incidence of Serious Adverse Device Effects (SADE), Adverse Events (AE), and Serious Adverse Events (SAE) [Time frame: From enrolment up to 12 months post-procedure]
• Changes in corneal alterations from baseline to 12 months. [Time frame: From baseline up to 12 months post-procedure]
• Changes in total and epithelial corneal thickness (central and minimum) from baseline to 12 months. [Time frame: From baseline up to 12 months post-procedure]
• Changes in IOP from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in corrected IOP (bIOP) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in macular central thickness from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in Endothelial Cell Count (ECC) from baseline to 12 months [Time frame: from baseline up to 12 months post-procedure]
• Subjective numeric scale related to several ocular symptoms [Time frame: From baseline to 12 months post-procedure]

Secondary outcome measures (12)

• Changes in Best Distance Spectacle Corrected Visual Acuity (BDSCVA) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in topographic keratometry values from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in topographic and refractive astigmatism from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in Manifest Refraction Spherical Equivalent (MRSE) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in Symmetry Index (SI) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in Center-Surrounding Index (CSI) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Assessment of the topographic centration of the implant [Time frame: From surgery up to 12 months post-procedure]
• Changes in Uncorrected Visual Acuity (UNCVA) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in Best Corrected Visual Acuity with rigid gas permeable contact lens (RGP-BCVA) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in biomechanical corneal properties expressed as Corneal Hysteresis (CH) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in biomechanical corneal properties, expressed as Deformation Amplitude Ratio (DA Ratio) from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]
• Changes in biomechanical corneal properties, expressed as Integrated Radius from baseline to 12 months [Time frame: From baseline up to 12 months post-procedure]

Eligibility criteria

Inclusion criteria

• Signed and dated informed consent form.
• Male and female ≥ 18 years old.
• Not recommended for ICRS.
• Recommended for keratoplasty.
• Minimum corneal thickness ≥ 350 μm.
• Best Distance Spectacle Corrected Visual Acuity (BDSCVA) with the ETDRS test ≥ 0.30 logMAR (<= 0,50 decimal notation).
• BCVA with RGP contact lens with the ETDRS test 10 letters or more than BCVA with spectacles.
• Have stable or stabilized disease for 12 months (in case of crosslinking, it must have been done at least 12 months prior to intervention).
• Have a KC stage 3-4 according to Investigator's judgement, with a central K readings > 47.2 D and RMS of coma aberration > 2.5 μm.
• Have no known or suspected allergy to nickel.
• Female subject of childbearing potential is eligible to participate if declaring she is not pregnant, or not breastfeeding and agree to use highly effective contraception (defined as method which results in a failure rate of <1% annually) and must abstain from egg donation or storage throughout the study period.

Exclusion criteria

• Inability of patient and/or relatives to understand the clinical investigation procedures and thus inability to give informed consent.
• Untreated progressive KC.
• Single functioning eye.
• Other ocular diseases (eyelids malposition, uveitis, ocular hypertension, glaucoma, cataract, retinal disorders) or corneal surgeries (refractive corneal surgery, keratoplasty), except corneal crosslinking.
• Systemic collagenopathies and/or vasculitis, and other diseases that in the opinion of the principal Investigator, may be contraindicated.
• Suspected or known intolerance or hypersensitivity to any of the treatments indicated in the CIP and/or to any component of the device (i.e. nickel).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma

Spain · 1 center

• Instituto de Microcirugía Ocular de Barcelona (IMO) — Barcelona

Identifiers

NCT: NCT06451718 · REMKERA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗