A Prospective, Open, Multicenter Clinical Trial With One Cohort Analysing the Efficacy and Safety of MINIject in Patients With Open Angle Glaucoma Uncontrolled by Topical Hypotensive Medications
Phase: NA
Conditions: Open Angle Glaucoma
Sponsor: iSTAR Medical

 
 
 
 
Clinical Study: 
A PROSPECTIVE, OPEN, MULTICENTRE CLINICAL TRIAL WITH 
ONE COHORT ANALYSING THE EFFICACY AND SAFETY OF 
MINIJECT IN PATIENTS WITH OPEN ANGLE GLAUCOMA 
UNCONTROLLED BY TOPICAL HYPOTENSIVE MEDICATIONS 
(ISM04) 
 
 
ClinicalTrials.gov identifier: 
NCT03193736 
 
 
Date of the document: 
17Jul2017 

 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
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Clinical Investigational Plan  
 
 
 
 
A PROSPECTIVE, OPEN, MULTICENTRE CLINICAL TRIAL WITH ONE 
COHORT ANALYSING THE EFFICACY AND SAFETY OF MINIJECT IN 
PATIENTS WITH OPEN ANGLE GLAUCOMA UNCONTROLLED BY 
TOPICAL HYPOTENSIVE MEDICATIONS 
_______________________________________________________ 
 
Synopsis 
according to EN ISO 14155:2011 
 
 
 
Medical Device Name:  
MINIject  
 
Clinical Trial Identifier:  
ISM04  
 
CIP Version:   
Version 3.0  
 
Release date  
17-JUL-2017 
 
 
 
 
This document includes confidential and privileged information and data that contain trade secrets which 
are property of ISTAR Medical. This information must not be made public without prior written permission 
of ISTAR Medical. This document may be disclosed to and used by the staff that conducts the clinical 
trial at a clinical investigational site. 

Synopsis 
 
 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
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Acronym  
MINIject Study  
Title 
A prospective, open, multicenter clinical trial with one cohort analyzing 
the efficacy and safety of MINIject in patients with open angle 
glaucoma uncontrolled by topical hypotensive medications 
Sponsor 
iSTAR Medical S.A. 
Avenue Sabin, 6 
1300 Wavre, Belgium 
Ethical 
Aspects 
Glaucoma is a complicated disease in which damage to optic nerve leads 
to progressive, irreversible vision loss. Glaucoma is the second leading 
cause of blindness. Glaucoma can be treated with eye drops, pills, laser 
surgery, traditional surgery or a combination of these methods. The goal 
of any treatment is to prevent loss of vision by lowering the IOP because 
vision loss from glaucoma is irreversible.  
If a surgery is needed the currently available options (trabeculectomy, 
available implants) do not promise a long-term effect and new devices 
are requested. STARflo MINIject is a promising new developed 
glaucoma device with a new structure and unique working method. 
Study purpose 
The aim of this study is to assess the efficacy and safety of the MINIject 
system in patients diagnosed with open angle glaucoma uncontrolled by 
topical hypotensive medications. 
Investigational 
Device and 
procedure  
MINIject is an integrated system comprising a minimally-invasive 
Glaucoma Drainage Implant and a Delivery Tool.  
The Delivery Tool is configured for inserting the implant into the sub-
scleral location through an ab-interno minimally-invasive approach. It is 
single-use. 
Device options to be evaluated in this study:  
Implant CS 600 with Curved Shaft. 
Intervention:  
The intervention is to be performed stand-alone. 
Indication 
 
 
MINIject is indicated in adult, male and female patients diagnosed with 
open angle glaucoma, and where the progression of glaucoma is not 
adequately controlled by topical hypotensive medications. 
MINIject is intended to be used to reduce the intraocular pressure (IOP) 
by channeling aqueous humor out of the anterior chamber to a sub-
scleral location, thus enhancing the physiological uveoscleral outflow.  
 
 
 

Synopsis 
 
 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
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Design 
Baseline and evaluation time points: 
Screening
/ Baseline 
Follow-up 1 day / 1 week / 2 weeks 
/ 1 Month / 3 Months 
Follow-up 6 / 12 / 18 / 24 Months 
patient 
inclusion 
Safety evaluation 
safety and efficacy evaluation  
medicated 
diurnal 
IOP 
baseline 
single point IOP measurement 
medicated diurnal IOP  
This prospective, non-comparative, open, multi-center, interventional clinical 
investigation is designed as one cohort study and intended to show the 
efficacy and safety of the MINIject system consisting of the CS 600 MINIject 
implant and the delivery tool with curved shaft. 
In total 25 patients will be enrolled in approximately 5 sites in Panama, India 
and Europe (France or Germany). 
The study will evaluate the efficacy and safety of the implant and IOP 
lowering effects with or without glaucoma medications. The procedure will be 
a stand-alone surgery. Overall, the patient will be asked to attend at 10 visits 
and perform several examinations up to 24 months after surgery. 
The primary efficacy objective of the present study is to show the IOP 
reduction under medication 6 months after surgery compared to medicated 
diurnal IOP at screening. 
The sponsor will evaluate the ease of use of the delivery tool based on 
questionnaires completed by the surgeons after surgery. 
Primary 
study 
objective 
The primary objective is to show a reduction in medicated diurnal IOP 
between screening/baseline visit and medicated diurnal IOP at 6 months after 
surgery. 
Secondary 
study 
objectives  
 
 
To test the reduction in medicated diurnal IOP between screening/baseline visit 
and medicated diurnal IOP 12 months and 24 months after surgery. 
To assess the safety of the MINIject in terms of nature and severity of Adverse 
Events (AE/SAE), Adverse Device Effects (ADE/SADE) and Unanticipated 
Adverse Device Effect (UADE)*.  
To assess the rate of peripheral and central corneal endothelial cells density-
loss. 
To assess the rate defined as: 
• 
Complete success: diurnal IOP ≤ 21mmHg and > 5mmHg with a 
minimum 20% diurnal IOP reduction from baseline without the need for 
glaucoma hypotensive medication. 
• 
Qualified success: diurnal IOP ≤ 21mmHg and > 5mmHg with a 
minimum 20% diurnal IOP reduction from baseline with the concomitant 
use of glaucoma hypotensive medication.    
To assess the reduction of the number of hypotensive active ingredients 
compared to screening visit. 

Synopsis 
 
 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
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* referring to expected AEs for implantable glaucoma devices as listed in ANSI Z80.27.2014 
and FDA Guidance Premarket Studies of Implantable Minimally Invasive Glaucoma surgical 
(MIGS) Devices.  
Assessed 
Parameter 
The assessed parameters are listed in detail in Table 1 at the end of this 
synopsis. 
 
Patient 
selection 
Inclusion criteria 
Any patient is eligible for inclusion in this clinical investigation if all of the 
following criteria apply: 
Males or females, 18 years of age or older. 
Diagnosis of primary or secondary open angle glaucoma during 
screening/baseline visit or earlier.  
Grade 3 (open, 20-35 degrees) or grade 4 (wide open, 35-45 degrees) 
according to Shaffer Angle Grading System. 
Glaucoma not adequately controlled by one to four different topical 
hypotensive medication(s), given each for at least one month, as confirmed 
by 21 mmHg ≤ IOP ≤ 35 mmHg in the study eye at screening and baseline 
visits. 
Patient must be willing and able to return for scheduled study-related 
examinations.  
Patient must provide written informed consent. 
 
Exclusion criteria  
Any patient is not eligible for inclusion in this clinical investigation if one or 
more of the following criteria apply: 
 
Diagnosis of glaucoma other than open angle glaucoma (e.g. angle closure 
glaucoma) in the study eye.  
Grade 2 (narrow, 20 degrees), grade 1 (extremely narrow, less or equal to 10 
degrees) and grade 0 (closed or slit) according to Shaffer Angle Grading 
System. 
Neovascular glaucoma in the study eye. 
Corneal opacity or iridocorneal angle not visible through gonioprism in the 
study eye, preventing correct placement of the implant.  
Prior glaucoma surgery in the study eye, patient treated with argon laser 
trabeculoplasty or selective laser trabeculoplastry in the study eye may be 
eligible if treatment performed ≥ 90 days before screening visit.  
Visual field defect in the 10 degree central field in the study eye. 
Anticipated need for ocular surgery or retinal laser procedure in the study eye 
in the 12 months following surgery.  
Anterior chamber anatomic configuration of high risk for development of 
angle closure glaucoma in the study eye.  

Synopsis 
 
 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
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Clinically significant corneal disease (e.g., corneal dystrophy) in the study 
eye.  
Pre-existing ocular or systemic pathology that, in the opinion of the physician, 
is likely to cause postoperative complications following implantation of the 
device in the study eye. 
Evidence of crystalline lens subluxation or luxation in the study eye.  
Evidence of vitreous loss in the anterior chamber in the study eye.  
Clinically significant intra-ocular inflammation or infection, presence of ocular 
disease such as uveitis, ocular infection, severe dry eye, severe blepharitis, 
active proliferative/inflammatory retinopathy in the study eye. 
Presence of silicone oil in the study eye.  
Patients treated with systemic acetazolamide within 3 days before screening 
visit.  
Patients with poor vision (LogMar score: +1.0) in non-study eye, unless there 
is an expected benefit for the study eye, in the opinion of the investigator.  
Participation in any study involving an investigational drug or device within 
the past 3 Months. 
Only for women of childbearing potential: positive urine pregnancy test at 
screening.   
Individuals under tutorship or trusteeship. 
Quality 
Assurance 
During the clinical investigation, the sites will be visited by CRO staff to review 
the progress of the clinical investigation, review the data collected, conduct 
source data verification, (according to ISO 14155:2011(E); define the extend 
of source data verification) perform device accountability, identify issues and 
address their resolution. The aim of the monitoring of the clinical investigation 
is to ensure that the data collected is authentic, accurate and complete, to 
ensure the safety of the subjects and that the subject’s rights are protected, 
and to ensure that the clinical investigation is performed according to the 
approved clinical investigation plan and all applicable regulations and 
guidelines. 
Sample 
Size 
Sample size is obtained by a paired sample t-test, 2-sided, with alpha of 0.05 
and power of 0.9. The difference of interest is taken equal to 5.2 mmHg. 
Under the conservative assumption that 25% of subjects will drop out of the 
study, this treatment effect will be reduced to 0.75*5.2 = 3.9 mmHg if all 
patients are included in an ITT analysis. The variance of the difference in IOP 
between the month 6 visit and baseline is assumed to be at most equal to 
3²+5²=34, hence the standard deviation is taken equal to 5.83. Under these 
assumptions, the sample size required is equal to 25 patients. 
 
 
 
Statistical 
rationale 
for sample 
An IOP reduction ≥ 20% has been previously used as success criterion and 
thus can be defined as clinically meaningful. 

Synopsis 
 
 
 
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size calcu-
lation 
The mean baseline IOP of 26.0 mmHg ± 3.0 used for calculation is derived 
from published study results involving comparable study population; subjects 
with OAG uncontrolled by medication(s).  
The mean IOP at 6 months is estimated to 20.8 mmHg ± 5, the standard 
deviation is derived from published study results involving comparable 
devices.   
Based on these assumptions, the estimated sample size of 25, in order to 
obtain 16 completed subjects at 6 Months follow-up (endpoint for the primary 
objective).  
 

Synopsis 
 
 
 
 
 
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FLOW CHART  
 
Visit 0 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
  
Screen/ 
Baseline 
Surgery 
1 Day  
1 week 
  
2 weeks  
1 Month  
Safety evaluation 
3 Months  
6 Months  
Safety & Efficacy 
evaluation 
12 Months  
Safety & Efficacy 
evaluation 
18 Months 
Safety & Efficacy 
evaluation 
24 Months 
 Safety & Efficacy 
evaluation 
 GENERAL ASSESSMENTS 
Day - 42  to -1 
Day 0 
Day 1 
Day 5-9 
Day 12-16  
Day 21-35 
Day 70-98 
Day 168-196 
Day 335-425 
Day 510-600 
Day 700-790 
Signed informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demography/ relevant 
medical and ocular 
history/Glaucoma diagnosis 
X 
  
  
  
  
  
  
  
  
 
  
Inclusion /exclusion criteria 
X 
  
  
  
  
  
  
  
  
 
  
Urine pregnancy test (women 
of childbearing potential only) 
X 
  
  
  
  
  
  
  
  
 
  
Concomitant ocular & non-
ocular medications,  
X 
X 
X 
X 
X 
X 
X 
X 
X 
x 
X 
AE/SAE recording 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x 
X 
Implantation 
  
X 
  
  
  
  
  
  
  
 
  
Implant position assess by 
investigator’s judgment  
  
X 
  
  
  
  
  
  
  
 
  
Record video of surgery  
  
X 
  
  
  
  
  
  
  
 
  
Ease of use feedback 
questionnaires completed by 
investigator 
  
X 
  
  
  
  
  
  
  
 
  
QOL questionnaire, CIGTS sub-
part 
X  
  
  
  
  
  
  
X 
X 
x 
X 
 
 
 

Synopsis 
 
 
 
 
 
ISM04 - CIP Version 3.0 – 17 Jul 2017 
 
  
 
 
 
 
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Visit 0 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
  
Screening/ 
Baseline 
Surgery 
1 day 
1 week  
 
2 weeks 
1 Month 
 Safety evaluation 
3 Months 
6 Months 
Safety & Efficacy 
evaluation 
12 Months  
Safety & Efficacy 
evaluation 
18 Months  
Safety & Efficacy 
evaluation 
24 Months  
Safety & Efficacy 
evaluation 
 OCULAR ASSESSMENTS 
Day -42  to -1 
Day 0 
Day 1 
Day 5-9 
Day 12-16  
Day 21-35 
Day 70-98 
Day 168-196 
Day 335-425 
Day 510-600 
Day 700-790 
BCVA  
X 
  
 X 
X 
X 
X 
X 
X 
X 
x 
X 
IOP, Goldmann Appl. 
Tonometry, diurnal (8:00 AM, 
12:00 AM, 4:00 PM) 
X 
  
  
  
  
  
  
X 
X 
x 
X 
IOP (Single time point) 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Visual field testing (Octopus 
or Humphrey) 
X 
  
  
  
  
X 
X 
X 
X 
x 
X 
Optic disc photograph of 
the optic nerve  
x 
 
 
 
 
x 
x 
x 
x 
x 
x 
Vertical C/D ratio 
X 
  
  
  
  
X 
X 
X 
X 
x 
X 
Central corneal thickness 
(pachymetry)  
X 
  
 
 
 
 
 
X 
X 
x 
X 
Gonioscopy, angle grading 
using Shaffer grading 
X 
  
  
  
  
  
  
  
  
 
  
Recording  Gonioscopy image 
  
X 
  
  
  
X 
  
  
  
 
  
Slit lamp examination  
X 
  
X 
X 
X 
X 
X 
X 
X 
x 
X 
Dilated fundus examination  
 X 
  
X 
X 
 
X 
 
X 
X 
x 
X 
Peripheral and central 
specular microscopy 
X 
  
  
  
  
  
  
X 
X 
x 
X 
Eye symptoms 
X 
  
X 
X 
X 
X 
X 
X 
X 
x 
X 
Assess Implant position (UBM) 
  
 
  
 X 
  
  
  
 X 
X 
x 
X 
Table 1: Flow chart for cohort, general and ocular assessments. All ocular assessments (except BCVA) are to be done on study eye only, except at screening visit, where the 
assessments are to be done on both eyes.