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

Keratoconus Clinical Trial

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 (KC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06451718
• Other study ID #: REMKERA
• Status: Recruiting
• Phase: N/A
• Start date: May 7, 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Fundacio De Recerca Del Instituto De Microcirugia Ocular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Study is a first in human clinical study addressed to evaluate the safety and efficacy of a novel intra-corneal nitinol device (Investigational Device; GROSSO® implant) for the treatment of advanced keratoconus disease of the eye.

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 > 53.00 D and RMS of coma aberration > 3.5, which are not eligible 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female = 18 years old

• Not suitable for ICRS and are recommended for keratoplasty

• Best distance spectacle corrected visual acuity (BDCSVA) 1.30 - 0.40 logMAR (0.05-0,40 decimal notation)

• Have stable or stabilized disease for 12 months (in case of cross-linking, it must have been done 12 months prior to intervention)

• Have a KC stage 3-4 (Amsler-Krumeich) with a Central K readings > 53.00 D and RMS of coma aberration > 3.5.

• Signed and dated informed consent form

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

• Minimum Corneal thickness < 400 µm

• 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

Related Conditions & MeSH terms

• Keratoconus

Intervention

Device:
• Intracorneal implantation
Intracorneal implantation of the nitinol investigational device

Locations

Country	Name	City	State
Spain	Instituto de Microcirugía Ocular de Barcelona (IMO)	Barcelona	Bar

Sponsors (1)

Lead Sponsor	Collaborator
Fundacio De Recerca Del Instituto De Microcirugia Ocular

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent adverse events , classification and related severity	Assessments, classification and related severity of Serious Adverse Device Effects (SADE), Adverse Events (AE) and Serious Adverse Events (SAE) and	6 months follow up
Primary	Slit lamp corneal assessment. Observations will be graded as follows:0- Absence 1- Mild 2- Moderate 3- Severe	Corneal inflammation; Corneal infection; Corneal neovascularization; Corneal stromal lysis; Corneal melting; Corneal stromal infiltration; Corneal neo vessels; Persistent corneal epithelial defects	6 months follow up
Primary	Epithelial corneal thickness assessments	Changes in total and epithelial corneal thickness (central and minimum)	6 months follow up
Primary	Intraocular pressure (IOP) assessments	Changes in IOP	6 months follow up
Primary	Corrected IOP (bIOP) assessments	Changes in bIOP	6 months follow up
Primary	Macular central thickness assessments	Changes in macular central thickness	6 months follow up
Primary	Corneal endothelium assessments	Change in the number of cells/mm^2 in the corneal endothelium	6 months follow up
Primary	Best Distance Spectacle Corrected Visual Acuity (BDSCVA)	Changes in BDSCVA	6 month follow up
Primary	Subjective numeric scale related to several ocular symptoms, graded from 0 to 10. lower scores reflect better symptomatology outcome	Subjective numeric scale elated to pain, foreign body sensation, tearing, photophobia, glare and halos.	6 month follow up
Secondary	Measurement of topographic keratometry values	Changes in topographic keratometry values maximum keratometry(Kmax), minimum Keratometry (Kmin) steep, and average keratometry (Km)	6 month follow up
Secondary	Measurement of topographic astigmatism	Changes in topographic astigmatism	6 month follow up
Secondary	Measurement of refractive astigmatism	Changes in refractive astigmatism	6 month follow up
Secondary	Measurement of manifest refraction sphere equivalent (MRSE)	Changes in MRSE	6 month follow up
Secondary	Measurement of irregularity index (IR)	Changes in IR from baseline to 6 months follow up. IR can be classified as low when <0.077 and high when = 0.077	6 month follow up
Secondary	Assessment of the centration of the intracorneal implant	Assessment of the corneal coordinates of the centration of the intracorneal implant	6 month follow up
Secondary	Measurement of Uncorrected Visual Acuity (UCVA)	Changes of UCVA	6 month follow up
Secondary	Best Corrected Visual Acuity(BCVA) with rigid gas permeable(RGP) contact lens (RGP-BCVA)	Changes in RGP-BCVA	6 month follow up
Secondary	Measurement of Optical surface index (OSI) related to Optical Quality	Changes in OSI ussing a double pass system. Higher intraocular scatter corre- lates with high OSI. OSI is calculated by the ratio between light in the periphery (circle of a radius between 12 and 20 mins of arc) and in the central peak (circle of a radius of 1 min of arc) of the DP image of the point spread function (PSF)	6 month follow up
Secondary	Measurement of Root Mean Square (RMS) related to Optical Quality	Changes in RMS	6 month follow up
Secondary	Measurement of biomechanical properties and characterization of the cornea by measuring Deflection Amplitude Ratio (DAR: Deflection Amplitude Ratio)	Changes in biomechanical properties. DAR: It is the ratio of the central corneal deflection to the average of 2 points 1.0 mm (DAR1) or 2.0 mm (DAR2) either side of the centre. Stiffer corneas would have a lower DA because the corneal centre and the cornea at 1.0 or 2.0 mm deflect at the same time, while a higher DA indicates that the central cornea deflects more than the average corneal deflection at 1.0 or 2.0 mm, whereas a higher DA indicates that the central cornea deflects more than the average corneal deflection at 1.0 or 2.0 mm. central cornea deviates more than the average of the other 2 points, which corresponds to a softer tissue.	6 month follow up
Secondary	Measurement of biomechanical properties and characterization of the cornea by measuring ,Integrated Radius	Changes in biomechanical properties. Integrated Radius: A dynamic corneal deformation response parameter that represents the reciprocal of the radius during the state of maximum corneal concavity. A larger concave radius is associated with greater resistance to deformation, i.e. a stiffer cornea. The larger the integrated inverse radius and the maximum inverse radius, the lower the resistance to deformation and the lower the corneal stiffness.	6 month follow up
Secondary	Measurement of biomechanical properties and characterization of the cornea by measuring, Ambrósio Relational Thickness horizontal (ARTh)	Changes in biomechanical properties. Ambrósio Relational Thickness horizontal (ARTh). Corneal thickness is measured using the Scheimpflug horizontal image. This allows calculation of the rate of increase in corneal thickness from the apex towards the nasal and temporal sides. The characterisation of the thickness profile allows the calculation of the Ambrósio relational thickness across the horizontal meridian, which is a relative simplification of the tomographic relational thickness calculations also provided by Pentacam.	6 month follow up
Secondary	Measurement of biomechanical properties and characterization of the cornea by measuring Stiffness Parameter-A1 (SP-A1) and Stress-Strain Index (SSI)	Changes in biomechanical properties. Stiffness Parameter-A1 (SP-A1). It is defined as the pressure resulting at first flattening from the difference between the air puff pressure at the corneal surface and the biomechanically corrected IOP, divided by the deflection amplitude. It is determined using the displacement of the apex from the resting state to the first flattening. This value has been clinically proven to be useful in the assessment of QC with the highest sensitivity and specificity of each of the parameter values. Higher values indicate stiffer corneas. Measured in mmHg/mm.	6 month follow up
Secondary	Measurement of biomechanical properties and characterization of the cornea by measuring Stress-Strain Index (SSI)	Changes in biomechanical properties. Stress-Strain Index (SSI). Parameter for estimating the material stiffness of corneal tissue, independent of IOP and corneal geometry. The stress/strain curve describes the elastic properties of the cornea. The curves are shifted to the right if the cornea is soft and to the left if it is stiff. The SSI index describes the position of the curve. A value of 1 indicates average elasticity, a value less than 1 indicates softer behaviour and a value greater than 1 indicates stiffer than average behaviour.	6 month follow up
Secondary	Measurement of vision Related Quality of Life (VRQoL)	Changes in the score of the questionnaire VRQoL. All items are scored so that a high score represents a better quality of life. Each item is converted to a 0 to 100 possible range, so that the lowest and highest possible scores are set at 0 and 100 repectively. The analyzed items are: Clarity of vision, expectations, Near vision, far vision, diurnal fluctuations, activity limitations, glare, symptoms, dependence on correction, worry, suboptimal correction, appearance, satisfaction with correction	6 month follow up
Secondary	Assessment of the corneal applanation	Changes of the corneal curvature or applanation	6 month follow up