Evaluation of EndoZip System in Obese Patients Who Failed to Reduce Weight With Non-surgical Weight-loss Methods
Phase: NA
Conditions: Obesity
Sponsor: Nitinotes Surgical Ltd.

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 1 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
1 of 83 
Title Page 
Clinical Investigational Plan (CIP) INFORMATION 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
CIP Number: 
CL00003 
Version Date: 
January 13, 2021 
Revision: 
1.0 
Sponsor: 
NiTiNotes Ltd. 
Address: 5 Haeshel   st., PO box 3158, Caesarea, Israel 
Tel: +972-4-
 
8876698  
Fax: +972-4- 8864385 
 
This document is property of NiTiNotes Ltd, its contents are CONFIDENTIAL and shall not be disclosed, 
disseminated, copied or used, without a written permission. 
 
 
Summary of Changes to CIP 
Revision 
Section 
Description of Change 
Reason for Change 
NA 
NA 
NA 
NA 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 2 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
2 of 83 
1.0 Signature Page 
Principal Investigator Signature Page 
Title: 
Evaluation of EndoZipTM AS System in Obese Patients 
CIP Number: 
CL00003 
Version Date: 
January 13, 2021 
Revision: 
1.0 
 
I, the undersigned, have read and understood the protocol specified above and agree on its content. I 
agree to perform and conduct the study as described in the protocol and in accordance with the 
relevant laws/regulations and standards outlined in the Clinical Trial Agreement. 
 
________________________    ____________________________    ______________________ 
Name 
Signature 
 
Date 
 
Sponsor representative signature 
 
Hagit Ephrath   
VP QA, Regulatory and Clinical Affairs_   
 
________________________    ____________________________    ______________________ 
Name 
Signature 
 
Date 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 3 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
3 of 83 
2.0 Table of Contents 
1.0 
Signature Page ................................................................................................................................. 2 
2.0 
Table of Contents ............................................................................................................................. 3 
3.0 
Protocol Synopsis ............................................................................................................................. 8 
4.0 
Acronyms and Definitions .............................................................................................................. 20 
5.0 
Introduction ................................................................................................................................... 21 
5.1 
Background ................................................................................................................................. 22 
5.1.1 
Applicable epidemiological background ............................................................................. 22 
5.1.2 
Available treatment modalities........................................................................................... 22 
5.1.3 
Study Rationale ................................................................................................................... 23 
6.0 
Investigational Device .................................................................................................................... 24 
6.1 
General Description .................................................................................................................... 24 
6.1.1 
EndoZip Main components ................................................................................................. 25 
6.1.2 
EndoZip Disposable Device ................................................................................................. 25 
6.1.3 
EndoZip Electrical Power Supply (Reusable) ....................................................................... 26 
6.2 
Pre-clinical data ........................................................................................................................... 27 
6.3 
Clinical data to Date .................................................................................................................... 27 
6.3.1 
Additional Information ........................................................................................................ 28 
7.0 
Benefit - Risk Assessment .............................................................................................................. 29 
7.1 
Potential Benefits ........................................................................................................................ 29 
7.2 
Anticipated Risks ......................................................................................................................... 30 
7.3 
Benefit – Risk Assessment........................................................................................................... 31 
8.0 
Study Objectives ............................................................................................................................ 31 
8.1 
Primary objectives....................................................................................................................... 31 
8.2 
Secondary objectives: ................................................................................................................. 31 
9.0 
Study Endpoints ............................................................................................................................. 31 
9.1 
Primary endpoints ....................................................................................................................... 31 
9.2 
Secondary endpoints .................................................................................................................. 32 
10.0 
Study Design .................................................................................................................................. 32 
10.1 
Study Flow Chart ..................................................................................................................... 33 
11.0 
Patient Selection and Enrollment .................................................................................................. 33 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 4 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
4 of 83 
11.1 
Inclusion Criteria ..................................................................................................................... 34 
11.2 
Exclusion Criteria ..................................................................................................................... 34 
11.3 
Withdrawal Criteria ................................................................................................................. 35 
11.4 
Selection of Investigators and Training ................................................................................... 36 
12.0 
Study Procedures ........................................................................................................................... 36 
12.1 
Clinical Laboratory Investigation ............................................................................................. 36 
12.2 
Vital Signs ................................................................................................................................ 37 
12.3 
Body Height, Weight and Waist Circumference ..................................................................... 37 
12.4 
Endoscopy Procedure ............................................................................................................. 38 
12.5 
Assessment of Adherence ....................................................................................................... 38 
12.6 
Quality of Life influence and Phycological Health Questionnaire........................................... 38 
12.7 
Home Sleep Apnea Test (HSTS) ............................................................................................... 39 
12.8 
Gastric Emptying Breath Test (GEBT) ...................................................................................... 39 
12.1 
Usability Assessment .............................................................................................................. 41 
13.0 
Study Schedule and Activities ........................................................................................................ 41 
13.1 
Visit 1 - Screening and Informed Consent ............................................................................... 41 
13.1.1 
Recruitment visit: ................................................................................................................ 42 
13.1.2 
Screen Failures .................................................................................................................... 42 
13.2 
Randomization ........................................................................................................................ 42 
13.3 
Visit 2 - EndoZip Procedure Day .............................................................................................. 42 
13.4 
Visit 3 – Follow Up 1 Week Post Procedure (7-10 days after the procedure) ........................ 44 
13.5 
Visit 4 – Follow Up 1-month Post Procedure .......................................................................... 44 
13.6 
Visit 5 – Follow Up 2 months Post Procedure ......................................................................... 45 
13.7 
Visit 6 – Follow Up 6 months Post Procedure ......................................................................... 45 
13.8 
Visit 7 – Follow Up 12 months Post Procedure ....................................................................... 46 
13.9 
Additional Follow Ups ............................................................................................................. 47 
13.10 
Schedule of Events .................................................................................................................. 48 
13.11 
Required Concomitant Medications or Therapies .................................................................. 52 
13.11.1 
Concomitant Medications, Treatments, and Procedure ................................................ 52 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 5 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
5 of 83 
13.11.2 
Reduce Medications, Treatments, and Procedure ......................................................... 52 
14.0 
Statistical Analysis .......................................................................................................................... 52 
14.1 
Sample Size Determination ..................................................................................................... 52 
14.2 
Description of statistical methods .......................................................................................... 53 
14.2.1 
Analysis of Populations ....................................................................................................... 53 
14.2.2 
General Methods: ............................................................................................................... 53 
14.2.3 
Handling of the Type I Error ................................................................................................ 53 
14.3 
Demographic, Medical history, and Baseline characteristics ................................................. 54 
14.4 
Primary Endpoint Analysis ...................................................................................................... 54 
14.4.1 
Subset Analysis of the primary endpoint: ........................................................................... 54 
14.5 
Safety Analysis ........................................................................................................................ 54 
14.6 
Secondary Endpoints Analysis .................................................................................................... 55 
14.7 
Interim Analyses ...................................................................................................................... 56 
15.0 
Adverse Events (AEs) and Complications ....................................................................................... 56 
15.1 
Adverse Event (AE) .................................................................................................................. 56 
15.2 
Serious Adverse Event (SAE) ................................................................................................... 56 
15.3 
Serious Health Threat ............................................................................................................. 57 
15.4 
Adverse Device Effect (ADE) ................................................................................................... 57 
15.5 
Serious Adverse Device Effect (SADE) ..................................................................................... 57 
15.6 
Unanticipated Serious Adverse Device Effect (USADE) .......................................................... 57 
15.7 
Adverse Event Severity Classification ..................................................................................... 57 
15.8 
Adverse Event Relationship Classification .............................................................................. 58 
15.9 
Adverse Event Outcome Classification ................................................................................... 58 
15.10 
Device Deficiencies ................................................................................................................. 59 
15.11 
Adverse Event Recording and Reporting ................................................................................ 59 
15.11.1 
Data Safety and Monitoring Board (DSMB) .................................................................... 59 
15.12 
Reporting Responsibilities ....................................................................................................... 60 
16.0 
Ethics and Compliance ................................................................................................................... 61 
16.1 
Statement of Compliance ....................................................................................................... 61 
16.2 
Protocol Compliance ............................................................................................................... 62 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 6 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
6 of 83 
16.3 
Institutional Review Board/Institutional Ethics Committee (IRB/IEC) .................................... 62 
16.4 
Patient Informed Consent ....................................................................................................... 62 
16.5 
Insurance ................................................................................................................................. 62 
16.6 
Confidentiality ......................................................................................................................... 63 
16.7 
Use of Data and Publications .................................................................................................. 63 
17.0 
Monitoring Procedures .................................................................................................................. 64 
17.1 
Data Collection and Processing ............................................................................................... 64 
18.0 
Study Supplies and Device Accountability ..................................................................................... 65 
18.1 
Packaging ................................................................................................................................ 65 
18.2 
Labeling ................................................................................................................................... 65 
18.3 
Inventory Control .................................................................................................................... 65 
18.4 
Retention of Records .............................................................................................................. 66 
18.5 
Study Completion/Termination of Study ................................................................................ 66 
19.0 
General Information ...................................................................................................................... 66 
19.1 
Study Contact Information ...................................................................................................... 66 
19.2 
Use of Data and Publications .................................................................................................. 67 
20.0 
REFERENCES ................................................................................................................................... 68 
21.0 
Appendix A: Post Procedure Regime ............................................................................................. 69 
21.1 
Pre-Procedure diet .................................................................................................................. 69 
21.2 
Post Procedure Diet ................................................................................................................ 69 
21.3 
Phase 1: Clear Liquids Only ..................................................................................................... 70 
21.4 
Phase 2: Full Liquid Diet .......................................................................................................... 71 
21.5 
Phase 3: Semi-Liquid (Pureed) Diet ......................................................................................... 72 
21.6 
Phase 4: Semi-Solid Diet ......................................................................................................... 73 
21.7 
Phase 5: 1200 – 1500 Calories Diet ......................................................................................... 75 
21.8 
General Instructions ................................................................................................................ 77 
21.9 
Physical Activity ....................................................................................................................... 78 
22.0 
Appendix B – Usability Questionnaire (filled-in by the physician) ................................................. 79 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 7 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
7 of 83 
23.0 
Appendix C – Patients Diary (filled-in by the patients) .................................................................. 83 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 8 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
8 of 83 
3.0 Protocol Synopsis 
 
Protocol Number 
CL00003 
Protocol Title 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to reduce 
weight with non-surgical weight-loss methods 
Study Sponsor  
NiTiNotes,  
5 Haeshel st, P.O Box 3158, Caesarea 3079815, Israel  
Tel: +972 (4) 8876698 
Fax: +972 (4) 8864385 
Sponsor Representative 
Hagit Ephrath 
VP QA, Regulatory and Medical Affairs 
Study Type 
Pilot study 
Study Product 
EndoZipTM System (AS) 
Study Location 
Europe, Israel 
Study Centers 
1. Hospital Universitario HM Sanchinarro, Madrid, SPAIN 
2. Fondazione Policlinico Universitario Agostino Gemelli IRCCS (CERTT), 
Rome, Italy 
3. Rabin Medical Center, Petah Tikva, Israel 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 9 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
9 of 83 
 
Investigators 
1. Prof.  Gontrand Lopez-Nava 
2. Dr. Ivo  Boškoski 
3. Dr. Steven Shamah 
Study Duration 
The duration for each participant will be 12 months; the total study duration is 
expected to be approx. 18 months  
Study Design 
The study is planned as a multicenter, prospective, single-arm, open-label, 
controlled clinical trial.   
Planned 
Follow-Up 
Visits 
• 
Office visits: 1 week, and 1, 2, 4, 6, 8, 10, and 12 month(s) 
• 
Remote follow up (by Phone): 3, 5, 7, 9, and 11 month(s) 
• 
Endoscopy follow up: 2 and  6 months  
• 
Motility evaluation by Gastric Emptying Breath Test (GEBT): 6 months 
• 
Physical examination, vital signs, waist circumference and BMI: 1 week, 1, 
2, 4, 6, 8, 10 and 12 months  
• 
Blood tests: 2, 6 and 12 months 
• 
IWQOL-Lite: 2, 6 and 12 months 
• 
Sleep Apnea (only for the relevant population): 2, 6 and 12 months 
Patient Population 
Male and Female with obesity, BMI of 30-40 kg/m2, between the ages of 21 and 
70 who failed to reduce weight with non-surgical weight-loss methods 
Planned # of Patients 
Up to 45 patients  
Planned # of Sites 
Up to 5 clinical sites 
Planned # of Patients 
per Site 
Up to 20 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 10 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
10 of 83 
 
 
Study Objective 
The objective of this study is to evaluate the safety and effectiveness of the EndoZip 
system procedure, coupled with lifestyle modifications, for weight reduction in obese 
patients with BMI of 30-40 kg/m2. 
Study Procedures 
Visit 1: Baseline Screening Visit  
• 
After signing informed consent, patients will be screened for study eligibility 
by: 
• 
Eligibility Criteria  
• 
Demographics, Medical history, Obesity History   
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Laboratory evaluations (Hematology, CBC with differential, PTT, PT and INR, 
Comprehensive Metabolic Panel (Kidney and liver functions – blood glucose, 
HbA1c, Urinalysis, TSH, fasting lipid panel) 
• 
Motility evaluation by Gastric Emptying Breath Test (GEBT) 
• 
Influence of Weight on Quality of Life (IWQOL) questionnaire  
• 
Psychological health questionnaire-9 (PHQ-9) 
• 
Patients with diagnosed Sleep Apnea will be tested using WatchPAT 200  
Visit 2: Procedure Day  
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Pregnancy test 
• 
Electrocardiogram (ECG) evaluation 
• 
Endoscopy screening procedure  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 11 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
11 of 83 
• 
EndoZip Procedure 
• 
EndoZip’s Usability Questionnaire 
• 
Meeting with dietitians/nutritionists 
• 
AE / SAE 
Phone call follow up 
At day 1 after patient’s discharge to verify the patient’s well-being. 
Visit 3: Follow up 1 week after patient’s discharge day: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Meeting with dietitians/nutritionists - lifestyle modifications counseling 
• 
Concomitant medication  
• 
AE / SAE 
Visit 4: Follow up 1 month after procedure day 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Meeting with dietitians/nutritionists - lifestyle modifications counseling 
• 
Concomitant medication  
• 
AE / SAE 
Visit 5: Follow up 2 months after procedure day: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Meeting with dietitians/nutritionists - lifestyle modifications counseling  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 12 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
12 of 83 
• 
Laboratory evaluations (Hematology, CBC with differential, Comprehensive 
Metabolic Panel (Kidney and liver functions – blood glucose, HbA1c, 
Urinalysis, fasting lipid panel)  
• 
Endoscopy follow up procedure 
• 
IWQOL questionnaire 
• 
Concomitant medication  
• 
AE / SAE  
• 
Patients with diagnosed Sleep Apnea will be tested using WatchPAT 200 
Visit 6: Follow up 6 months after procedure day: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Meeting with dietitians/nutritionists - lifestyle modifications counseling 
Laboratory evaluations (Hematology, CBC with differential, Comprehensive 
Metabolic Panel (Kidney and liver functions – blood glucose, HbA1c, 
Urinalysis, TSH, fasting lipid panel) 
• 
Motility evaluation by Gastric Emptying Breath Test (GEBT) 
• 
Endoscopy procedure 
• 
IWQOL questionnaire 
• 
Concomitant medication  
• 
AE / SAE 
• 
Patients with diagnosed Sleep Apnea will be tested using WatchPAT 200 
Visit 7: Follow up 12 months after procedure day: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
• 
Body Weight, Height and Waist circumference 
• 
Meeting with dietitians/nutritionists - lifestyle modifications counseling 
• 
Laboratory evaluations (Hematology, CBC with differential, Comprehensive 
Metabolic Panel (Kidney and liver functions – blood glucose, HbA1c, 
Urinalysis, fasting lipid panel)  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 13 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
13 of 83 
• 
IWQOL questionnaire 
• 
Concomitant medication  
• 
AE / SAE 
• 
Patients with diagnosed Sleep Apnea will be tested using WatchPAT 200 
 
Additional follow up visits: 
Patients 
will 
receive 
brief 
(30min) 
telephone 
calls 
in 
the 
months 
that do not include in person visits (in months 3, 5, 7, 9, and 11 after the procedure). 
These counseling sessions are primarily designed to improve adherence to 
recommendations to consume a healthy diet and increase physical activity to promote 
weight loss and overall health.  
 
Additional in person visits  
In addition to the visits above, patients will visit the clinic in 4, 8, and 10 months after 
the procedures.  In these visits, patient will meet the physicians and the 
dietitians/nutritionists. These counseling sessions are primarily designed to improve 
adherence to recommendations to consume a healthy diet and increase physical 
activity to promote weight loss and overall health. 
Primary Endpoint 
The effectiveness of the EndoZip system will be assessed by the following co-primary 
endpoints: 
1. Mean percent of total body weight loss (%TBWL) after 12 months. 
2. Percentage of patients with a reduction in %TBWL of at least 5% at 12 
months.   
Secondary Endpoints 
The following secondary endpoints will be evaluated: 
1. Percent of excessive weight loss (%EWL) over 6 and 12 months. 
2. Reduction of weight and waist circumference over 6 and 12 months. 
3. Impact of EndoZip procedure on gastric motility at 6 months. 
4. Changes in Weight-related Quality of Life (IWQOL) Questionnaire scores at 6 
and 12 months 
5. Time analysis including procedure duration, anesthesia duration, patient 
recovery duration 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 14 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
14 of 83 
6. Change in comorbid conditions over 12 months evaluated by: 
a. Blood pressure 
b. Glucose, HbA1c 
c. Lipid levels (Total Cholesterol, LDL-C, HDL-C, and triglycerides) 
d. Sleep Apnea  
7. Usability evaluation and physician’s satisfaction based on a questionnaire  
Safety Endpoints 
The following safety variables will be recorded at regular intervals during the study: 
● Physical examination 
● Vital signs (blood pressure and heart rate - supine, pulse, body temperature, 
respiratory rate (RR) and SpO2) 
● Telemetry monitoring (continuous ECG, respiratory rate, SpO2 monitoring) 
during procedure and at recovery  
● Clinical laboratory tests (hematology, clinical chemistry, lipid profile and 
urinalysis) 
● Adverse event (AE) assessments 
● Monitoring of sleep apnea (If relevant) 
Safety will be characterized through a summary of the incidence of adverse events 
and 
serious 
adverse 
events 
by 
relation 
to 
study 
treatment. 
A Data Safety Monitoring Board (DSMB) will review and adjudicate all serious device 
related and non-related adverse events and any other events deemed necessary. 
Randomization 
NA- single arm study 
Eligibility Criteria 
Inclusion Criteria 
1. Age 21-70 
2. BMI ≥ 30 and ≤40 kg/m². 
3. Willingness to comply with the substantial behavioral modifications program 
as required by the procedure. 
4. Patients with history of failure with non-surgical weight-loss methods. 
5. Willingness to follow protocol requirements, including signed informed 
consent, routine follow-up schedule, completing laboratory tests, 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 15 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
15 of 83 
completing IWQOL questionnaire and completing the medically supervised 
diet and behavior modification program. 
6. Residing within a reasonable distance from the investigator's office and able 
to travel to the investigator to complete all routine follow- up visits. 
7. Ability to give informed consent. 
8. Women of childbearing potential (i.e., not post-menopausal or surgically 
sterilized) must agree to use adequate birth control methods. 
Exclusion Criteria 
1. Prior surgery of any kind on the gastrointestinal tract (except uncomplicated 
cholecystectomy or appendectomy). 
2. Patients with history of small bowel or colonic obstruction, and/or adhesive 
peritonitis and/or abdominal adhesions. 
3. Patients with any inflammatory disease  
4. Patients with history of cancer in the gastrointestinal tract. 
5. Potential upper gastrointestinal bleeding conditions such as a history of 
angioectasias. 
6. A known gastric mass or gastric polyps > 1 cm in size. 
7. Patients with TG >500 or LDL >190 
8. A known hiatal hernia > 4cm of axial displacement of the z-line above the 
diaphragm or severe or intractable gastro-esophageal reflux symptoms while 
on maximal medical therapy. 
9. A structural abnormality in the esophagus or pharynx such as a stricture or 
diverticulum that could impede passage of the endoscope. 
10. Patient with motility disorders of the GI tract or intractable constipation 
11. Patients with known coagulation disorder (INR >1.5) or on anticoagulation 
therapy. 
12. Type 1 diabetes or Type 2 diabetes with a HgbA1c >8 in 6 weeks prior the 
procedure or use of any medication for diabetes other than metformin. 
Patients with any serious health condition unrelated to their weight that 
would increase the risk of endoscopy  
13. Patients with chronic abdominal pain 
14. Patients with hepatic insufficiency or cirrhosis 
15. Patients that used an intragastric device for weight loss within 2 years prior 
to this study. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 16 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
16 of 83 
16. Patients with psychological health questionnaire-9 (PHQ-9) score of 10 or 
higher.  
17. Patients receiving daily prescribed treatment with high dose aspirin (> 
100mg daily), anti-inflammatory agents, anticoagulants or other gastric 
irritants. 
18. Patients with history or current abuse of drugs or alcohol 
19. Patients who are unable or unwilling to take prescribed proton pump 
inhibitor medication 
20. egg, milk, or wheat allergy (unable to go through the GEBT) 
21. Patients who are pregnant or breast-feeding. 
22. Patients who are taking medications that cause weight loss 
23. Patients with Severe cardiopulmonary disease or other serious organic 
disease which might include known history of coronary artery disease, 
Myocardial infarction within the past 12 months, poorly-controlled 
hypertension, required use of NSAIDs 
24. Patients taking medications on specified hourly intervals that may be 
affected by changes to gastric emptying, such as anti-seizure or anti-
arrhythmic medications 
25. Patients who are taking corticosteroids, immunosuppressants, and narcotics 
26. Symptomatic congestive heart failure, cardiac arrhythmia or unstable 
coronary artery disease. 
27. Pre-existing respiratory disease such as chronic obstructive pulmonary 
disease (severe COPD), pneumonia or cancer. 
28. Diagnosis of autoimmune connective tissue disorder (e.g. lupus, HIV, 
erythematous, scleroderma) or immunocompromised. 
29. Specific diagnosed genetic disorder such as Prader Willi syndrome (motility 
disorder) 
30. Eating disorders including night eating syndrome (NES), bulimia, binge eating 
disorder, or compulsive overeating 
31. Known history of endocrine disorders affecting weight such as uncontrolled 
hypothyroidism. 
Statistical Considerations 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 17 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
17 of 83 
Analysis Populations 
Full Analysis Set (FA): includes all enrolled patients, excluding the patients who 
enrolled in the  run-in period, who undergone EndoZip procedure. 
 
Modified Full Analysis Set (mFA): The modified full (mFA) analysis set will include all 
patients who have at least one post initiation follow up visit and met the study 
Eligibility Criteria.  
 
Per-Protocol (PP) analysis set: includes all patients from the mFA set who do not have 
any major protocol violations.   
 
Statistical Analysis of Analysis Sets 
Safety assessments will be performed on the FA analysis set.  
The mFA will serve as the principal data analysis set for the primary and secondary 
statistical efficacy endpoints.  The primary, secondary efficacy assessment will also 
be performed on the PP and FA cohorts for descriptive purposes and to show 
consistency of study results. 
Sample Size 
Estimation 
This is a pilot study that will include up to 45 patients; no statistical considerations 
were made to determine the sample size. 
Statistical Analyses 
General Methods: 
Statistical analyses will be mainly descriptive in nature. Any statistical tests if 
performed will be two-sided, unless otherwise stated.  
Study data will be summarized with descriptive statistics and presented in tables and 
figures. Continuous variables will be summarized by a mean, standard deviation, 
minimum, median and maximum and categorical variables by a count and 
percentage. If multiple measurements are taken in a single patient, statistics 
described below will be appropriately modified to accommodate the within patient 
correlation. 
Any deviation from specified statistical plan will be in addition to “per protocol” 
analysis and will be reported as such Post-hoc analysis will be conducted according 
to the existing data gathered, if necessary.   
 
 
Handling of the Type I Error 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 18 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
18 of 83 
 
The overall significance level for this study is 5%, confidence intervals will be two-
sided using a 95% confidence level, except for treatment by site interaction that will 
be tested at a significance level of 10%. 
 
Primary Endpoints 
The %TBWL at each visit will be calculated as 100*(Weight(BL) -Weight(Visit))/ 
Weight(BL), where weight is measured in kilograms. %TBWL will be summarized with 
descriptive statistics at each follow-up visit. 
%TBWL will be evaluated by using repeated measures analysis of covariance 
(ANCOVA MIXED model). Baseline weight, center and visit will be used as covariates. 
Baseline weight will be entered as a continuous variable so that the potential for co-
linearity problems will be minimized.  
The unstructured covariance matrix structure will be used. If the model doesn’t 
converge, then either the compound symmetry or autoregressive (whichever model 
has the lower AIC statistic) covariance matrix structure will be used instead. For this 
evaluation, no imputation of missing data is considered beyond the model estimates.  
The model estimated mean %TBWL at each visit will be presented with 95% 
confidence interval and level of significance. 
A count and percentage of patients achieving at least 5% TBWL will be presented 
with exact 95% confidence interval.  
 
Subset Analysis of the primary endpoint: 
Additionally, the %TBWL median, mean and standard deviation and percent of 
patients with greater than 5%TBWL will be summarized. Covariates may include 
demographic data (sex, age, BMI) or other baseline characteristics.  
 
Secondary Endpoints 
Excess Weight Loss % (EWL%) 
EWL% of patients at 1, 2, 6 and 12 month(s) by study group will be summarized with 
descriptive statistics with 95% confidence intervals. 
The percent excess weight loss (%EWL) will be calculated as (Weight(BL) – 
Weight(Visit)/ ExcessWeight(BL), where ExcessWeight(BL) is calculated as difference 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 19 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
19 of 83 
 
 
between the patient’s baseline weight in kilograms and the kilograms at which the 
patient’s BMI would be 25. 
 
Change of Weight and Waist Circumference Over 12 Months from Baseline  
Change from baseline in BMI at 1, 2, 6 and 12 month(s) by study group will be 
summarized with descriptive statistics with 95% confidence intervals. 
 
Changes in Weight-related Quality of Life (IWQOL) Questionnaire at 12 months  
 IWQOL questionnaire records will be summarized by study groups will be 
summarized with descriptive statistics with 95% confidence intervals. 
 
Time analysis 
Time analysis including procedure duration, anesthesia duration, patient recovery 
duration will be evaluated and will be summarized with descriptive statistics with 
95% confidence intervals 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 20 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
20 of 83 
4.0 Acronyms and Definitions 
ADE 
adverse device effect 
ADL 
activities of daily living 
AE 
adverse event 
ASADE 
anticipated serious adverse device effect 
CRF 
case report form 
CIP 
clinical investigation plan 
CRO 
contract research organization 
COTS 
commercial off the shelf 
CA 
competent authority 
DSMB 
data and safety monitoring board 
EC 
European commission 
ESD 
endo-Surgery Device 
FA 
full analysis (data set)  
FDA 
food and drug administration 
GEBT 
gastric emptying breath test 
GCP 
good clinical practice 
GLP 
good laboratory practice 
IB 
investigator's brochure 
ICF 
informed consent form 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 21 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
21 of 83 
ICH 
international Conference on Harmonisation 
IEC 
institutional ethics committee 
IFU 
instruction for use 
IRB 
institutional review board 
ISF 
investigator site file 
ISO 
international organization for standardization 
mFA 
modified full analysis (data set) 
NCA 
national competent authorities 
PI 
principal investigator 
PP 
per protocol (data set) 
RA 
regulatory authorities 
SADE 
serious adverse device effect  
SAE 
serious adverse event 
SOP 
standard operating procedure 
USADE 
unanticipated serious adverse device effect  
 
5.0 Introduction 
This document is a protocol for human research study. This study will be conducted in accordance with 
the applicable international standard of Good Clinical Practice, and institutional research policies and 
procedures.  
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 22 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
22 of 83 
5.1 
Background  
5.1.1 
Applicable epidemiological background 
Obesity is a global epidemic. In the last few decades, obesity has gained significance as a 
worldwide health problem. The World Health Organization (WHO) estimated that approximately 
1.5 billion adults (age 20 y or older) were overweight [1]. Currently, more than 30% of the US adult 
population is obese [2], which accounts for approximately 72 million obese Americans [3]. 
The morbidity associated with obesity is alarming serious health concern, with an increased 
incidence of metabolic syndrome, type 2 diabetes mellitus, hypertension, and many other 
comorbidities. 
5.1.2 
Available treatment modalities 
There are several alternatives to for the treatment of obesity (BMI of >30 kg/m2), which can 
be divided into the following: non-surgical treatments, medical devices, and surgery. Each 
alternative has its own advantages and disadvantages. A patient should fully discuss these 
alternatives with his or her physician to select the method that best meets expectations and 
lifestyle. 
Non-Surgical Treatments 
Non-surgical treatments for obesity include: 
• 
Diet, exercise, and behavioral modifications, and 
• 
Prescription weight loss medications. 
Several reports have suggested a rather high incidence of failure for obese patients to 
sustain long-term weight loss with any form of non-surgical treatment. 
Intra-Gastric Balloons 
Intra-gastric balloons are typically recommended for patients with a BMI 30-40 kg/m2. It is a 
temporary non-surgical obesity treatment that induces short-term weight loss by placing a soft, 
elastomeric balloon in the stomach, thus partially filling the stomach to achieve satiety. The 
Balloon is removed 6-12 months after placement. 
Obesity Surgery 
Bariatric surgery is typically recommended for patients with a BMI of at least 40 kg/m2, 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 23 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
23 of 83 
or a BMI of at least 35 kg/m2 with one or more obesity-related comorbid conditions. The 
most common types of bariatric surgery are described below. 
Roux-en-Y Gastric Bypass (RYGB) 
In a gastric bypass, the surgeon first constructs a proximal gastric pouch and then 
creates an outlet from the pouch to a limb of the small bowel. This results in a bypass 
of most of the stomach and duodenum.  
Vertical Sleeve Gastrectomy 
Vertical sleeve gastrectomy is a procedure which reduces the size of the stomach by 
surgical removal of a large portion of the stomach. The open edges are then sutured 
together to form a sleeve. The size of the stomach is permanently reduced without 
bypassing the intestines. Unlike RYGB, the stomach is not bypassed and there is no 
malabsorption component.  
Biliopancreatic Diversion Duodenal Switch 
The biliopancreatic diversion with duodenal switch is a procedure in which stomach 
removal is restricted to the outer margin, leaving a stomach sleeve with the pylorus 
intact. The small intestine is divided with one end attached to the stomach pouch. The 
majority of the small intestine is bypassed.  
Single Anastomosis (Omega Loop) Bypass “mini bypass” 
The mini bypass is a procedure in which the surgeon will reduce the size or volume of the 
stomach, similar to the gastric sleeve. This sleeve is then connected to the intestine, bypassing 
up to 200cm of the upper part of the intestine. 
In general, bariatric surgeries have shown, in multiple studies, to lead to significant and 
durable weight loss. However, it has been estimated that only 1% of eligible patients undergo 
bariatric surgery because of serious complications including perforation, hemorrhage, 
infections and bowel obstructions, limited access, cost, and patient preference [4].  
 
5.1.3 
Study Rationale 
NiTiNotes Ltd. has developed the EndoZip System which offers obesity treatment by an operator-
friendly endoscopic procedure generating an endoluminal gastroplasty that restricts the stomach 
and impairs motility.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 24 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
24 of 83 
The EndoZip system is designed to allow for the creation of multiple internal gastric 
segmentations in the stomach by using an endoscopic approach. The system allows the forming 
of wall-to-wall longitudinal attachments of the anterior and posterior stomach walls, creating 
multiple plications within. Another important determinant which predicts a favorable safety 
outcome is the minimally invasive nature of the procedure. 
The pre-clinical studies and initial human study (details are provided in 6.2 and 6.3), using an 
earlier configuration of the device, have proven to have excellent safety profile, and provided 
initial performance data. 
The aim of this study is to evaluate the updated device configuration of EndoZip system to 
establish the long-term safety and further validate the efficacy claim in the intended population. 
6.0 Investigational Device 
6.1 
General Description 
The EndoZipTM is an automatic, operator-friendly Endo-Surgery Device (ESD) designed to create multiple 
internal gastric segmentations in the stomach by using an endoscopic approach. The system applies a 
wall-to-wall longitudinal attachment of the anterior and posterior stomach walls, creating multiple 
plications within.  
The EndoZip is inserted to the stomach through a standard endoscopy designated Overtube. The device 
advancement and positioning in the stomach is visually guided by a small diameter endoscope inserted 
through device's dedicated channel. In addition, EndoZip is connected to a COTS (Commercial Off the 
Shelf) vacuum pump used in Endoscopy units / clinics.  
The system with the aid of the external vacuum pump, enables the approximation of the opposite 
stomach walls by extracting air from the chosen deployment site, i.e., the creation of a near vacuum 
state, causing the tissue segments to draw into the Bougie and create a narrowing for segmentation of 
the stomach.  
Following the approximation process, a custom designed needle is driven through the Bougie, (from its 
distal end toward it proximal end), passing the attached suture through the approximated tissue 
segments and creating the continuous plications within the stomach. Then the device enables tightening 
and cinching the approximated tissue segment with an integrated, dedicated clip. The procedure is 
completed with device retraction from the deployment site and a visual confirmation using a scope. The 
system provides suturing stage indication by a LED bar located in the device handle. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 25 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
25 of 83 
Per the IFU, up to five (5) systems, per the physicians’ judgement, may be used for the creation of 
multiple plications within the stomach. For the purpose of this study up to six (6) systems, per the 
physicians’ judgement, may be used for the creation of multiple plications within the stomach.    
The EndoZipTM System is made of biocompatible non absorbable materials widely used as surgical 
sutures. The system is supplied sterile.  
In addition, the EndoZip™ System is a minimally invasive procedure, a reproducible and easy to use 
device that can aid the obesity treatment by expanding the access and acceptability to a broad 
population segment. 
6.1.1 
EndoZip Main components 
The EndoZip system consists of a disposable device that controls the procedure and a reusable 
electrical power supply. 
6.1.2 
EndoZip Disposable Device  
The EndoZip disposable device comprises three main components: Bougie, Insertion Tube and 
Handle as depicted in Figure 1 below. 
 
Figure 1 – EndoZip Disposable Device 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 26 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
26 of 83 
Bougie 
The distal end of the device, referred as the “Bougie”, is designed to optimize the suturing 
mechanism. It contains a chamber that captures the tissue using a vacuum, to support full-
thickness sutures. In addition, the Bougie includes a steerable segment that facilitates device 
maneuvering. 
Insertion Tube (IT) 
The Insertion Tube (IT) connects the Handle and Bougie parts, supporting insertion and evacuation 
of air and CO2.  It also contains a channel for the endoscope passthrough. 
EndoZip Handle 
The EndoZip handle aids the physician to maneuver the device and position it in the desired 
abdominal area. In addition, it controls all suturing activity. The handle comprises 2 functional 
parts: 
• 
Motor unit: Includes motors and controllers to perform all required activities including 
stitching, tightening, clipping, and cutting of suture wire. The unit has a sensing mechanism 
that ensures that the stages after stitching are contingent upon the needle reaching its 
designated area. 
• 
Mechanical control unit: The mechanical control unit aids the physician to maneuver the 
device and position it in the desired abdominal area. 
 In addition, the EndoZip System comprises the following Disposable Components: 
• 
pinch clamps – 2 pinch clamps used to manage the vacuum via the EndoZip and the 
endoscope during the procedure.  
• 
Sealing Adaptor – A component located between the EndoZip system to the Overtube. 
6.1.3 
EndoZip Electrical Power Supply (Reusable)  
The EndoZip electrical power supply contains a unique and dedicated connector to the EndoZip 
disposable.  
The EndoZip System complies with the IEC 60601-1 Ed. 3.1, 60601-1-6 Ed. 3.0 safety standards and IEC 
60601-1-2 EMC standard. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 27 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
27 of 83 
For detailed description of the device please refer to the current version of the study Investigator’s 
Brochure (IB). 
6.2 
Pre-clinical data 
Several bench tests were performed with the EndoZipTM, to ensure that the device meets its design 
specifications and is safe for its intended use. Performance of the device was also evaluated, especially 
the mechanical properties, functional features and operational parameters.  
NiTiNotes conducted animal studies during the first prototype development to evaluate the safety of the 
EndoZip system under in-vivo conditions. A swine model was chosen as it has been used extensively as a 
gastrointestinal model due to its anatomic and physiologic characteristics which are similar to humans. 
Notably, despite being the best model animal for human, the swine model may be very challenging and 
represents the worst-case scenario for this study as the swine’s gastric capacity and surface tension are 
significantly greater compared with humans.   
In this experiment, that included application of the system and suturing it was proven that the system is 
capable to perform approximation of the stomach tissue segments (Anterior and Posterior segments) 
and to suture said segments one to the other using a continuous suturing. Furthermore, EndoZipTM was 
considered non-irritant as expected in histological evaluation and a normal reaction to such a suture was 
observed in the procedure surroundings. Unexpected adverse reactions were not observed.  
Although studies were performed on an earlier prototype device, the conclusion are valid to the final 
device as both configurations (i.e., prototype and final design) share similar suturing mechanism of 
action, meaning gripping and holding the tissue in the Bougie chamber using vacuum, and same needle, 
suture thread and clips’ materials. 
All components of the EndoZipTM, that come in direct contact with the patient, were deemed 
biocompatible in accordance with the ISO 10993 biocompatibility standards. 
For in-depth review of the pre-clinical investigations, please see the study Investigator’s Brochure (IB). 
6.3 
Clinical data to Date 
One clinical study has been conducted to date. The study was designed to evaluate the safety and the 
outcomes of the EndoZip prototype system with respect to obese patients’ weight loss in 6 months. It 
was a single arm, prospective single center study, conducted by Prof. Lopez-Nava at the Bariatric 
Endoscopy unit of HM Sanchinarro University Hospital, Madrid, Spain. The institutional review board 
approved the study. The study was conducted in accordance with the ethical principles detailed in the 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 28 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
28 of 83 
Declaration of Helsinki and was consistent with Good Clinical Practices recommendation 
(Clinicaltrials.gov, NCT03472196). The study results were published on January 2020 at Obesity Surgery 
Journal [OBES SURG (2020) 30:1696–1703]. 
Study Design - Patients in this study were instructed to be on a liquid diet and fast a day prior the 
procedure. BMI, waist circumference, blood tests and a Quality of life questionnaire were recorded prior 
the procedure. 
Patients were followed up 7-10 days, 6 weeks, 3 and 6 months after the procedure. In the follow up 
visits, changes in the patients’ well-being, blood tests outcomes, compliance with the diet instructions 
and weight were recorded. At 6 weeks, 3 and 6 months after the procedure, presence and location of 
the stiches by means of endoscopy, and quality of life were recorded. 
Results - Eleven obese class I and II patients are included in this analysis. 
The age range of the patients was 35-51 years, their average weight was 111.1 kg, their average height 
was 174 cm and their BMI (kg/m2) ranged from 30.2-39.7. 
Thirty-one (31) procedures were applied in 11 patients. All procedures (100%; 95% CI [89%,100%]) were 
completed successfully. 
All eleven patients reached 3-months and adhered until 6-month follow-up. The mean ±SD TBWL at 3-
month and 6-month was 14.8 ± 4.8 Kg and 17.8 ± 6.7 Kg, respectively (p<0.001). The mean ±SD %TBWL 
at 3-month and 6-month was 13.5 ± 4.7% and 16.2 ± 6.0%, and the mean ±SD %EBWL was 46.5 ± 28.6% 
and 54.3 ± 28.4%, respectively. 
The mean ±SD of waist circumference at baseline was 117 ± 9.4 and significantly (p<0.001) reduced 6 
months after the EndoZip procedure to mean ±SD of 100 ± 12.7. 
Safety evaluation - There were no adverse events related to the study. Two events unrelated to the device and 
/ or EndoZip procedure occurred during the study. 
6.3.1 
Additional Information 
For the completeness of this section it should be noted that in an expansion of the clinical study 
one technical failure, where the needle did not penetrate through the tissue smoothly and could 
not be retrieved, per the IFU instructions, from the stomach. The needle was retrieved 
endoscopically, and the patient received antibiotics to prevent any infection. The event has 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 29 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
29 of 83 
resolved with no clinical sequelae.  The event was classified as an anticipated and resolved serious 
adverse event. This event lead to a redesign of the Bougie portion of the device configuration. 
 
These and all other changes implemented in the improved device configuration (i.e., final device) 
were verified and validated in the bench testing mentioned above.  
7.0 Benefit - Risk Assessment 
7.1 
Potential Benefits 
EndoZipTM System is an automatic, operator-friendly ESD that allows the user to create multiple internal 
gastric segmentation in the stomach by using an endoscopic approach. The System generates an 
endoluminal gastroplasty that restricts the stomach and impair motility. Since this is an endoluminal 
approach, the potential for leaks has been significantly minimized. Also, this procedure is reversible and 
requires short recovery duration, and thus may be applied to a much wider patient population, by 
gastroenterologists as well as surgeons. 
NiTiNotes has performed several preclinical and clinical studies in the development process with 
prototypes of varying designs as with the final device configuration.  
In a First In Human study including 11 patients and 31 suture procedures, the first EndoZip prototype 
device presented promising safety and effectiveness results of %TBWL of 16.2 ± 6.0 at 6 months. No SAE 
related to the study occurred within the study duration. In an extended feasibility study a technical 
failure occurred and study was early terminated. The final design configuration includes improvements 
aim to minimize the likelihood of such an event.   
The following are potential benefits of the EndoZip™ System stratified by key stakeholders: 
Physicians:  
• 
An effective non-surgical, long lasting treatment.  
• 
Facilitate reduction in comorbidities. 
• 
User-friendly procedure that has a minimal learning curve and provides reproducible 
results (not operator-dependent). 
• 
Can be readily available for in clinic use, thereby improving patient access.  
• 
Lower risk profile while still providing clinically significant weight loss outcomes.  
• 
Short procedure with potential of cost reduction. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 30 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
30 of 83 
Patients: 
• 
Favorable safety profile with minimal trauma. 
• 
Effective non-surgical, long lasting treatment. 
• 
Potentially easier and shorter recovery. 
 
Healthcare System: 
• Lower expenditure - Patients are expected shorter recovery and reduced complications 
• Procedure can be conducted by endoscopists and surgeons 
7.2 
Anticipated Risks  
The EndoZip system is an ESD, hence the complication associated with using it are anticipated to be 
similar to other endoscopic suturing devices such as OverStitch™ Endoscopic Suturing System (K181141). 
As with any intragastric suturing procedure, using the EndoZip System may lead to the following 
potential risks: 
1. Severe tissue trauma that requires operation (e.g., perforation, obstruction, unscheduled 
implant removal due to severe pain or other symptoms, etc.). 
2. Severe patient infection / biologic reaction that requires intensive care unit treatment. 
3. User electric shock/injury hazard/Fire. 
4. Moderate tissue trauma that requires therapy other than a surgical operation (e.g., ulcer, GI 
bleeding, GERD, etc.). 
5. Minor patient infection / biologic reaction. 
6. Minor user infection / biologic reaction. 
7. Minor tissue trauma and/or patient discomfort that can be managed with prescription drugs 
and / or mild intervention (e.g., dehydration, cutaneous bleeding, laceration, esophagitis, 
gastritis, severe vomiting, etc.). 
8. Extended procedure time. 
9. Failed procedure. 
10. Equipment damage to endoscope. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 31 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
31 of 83 
11. Patient discomfort (e.g. nausea, vomiting, bloating, cramps, diarrhea, constipation, etc.). 
12. User injury hazard. 
13. User inconvenience. 
All risks of using EndoZip were mitigated by design and verification tests. NitiNotes’ risk management 
process complies EN ISO 14971:2019.  The potential residual risk following the mitigations are all 
acceptable (for more details please refer to "Risk analysis report"). 
As described in the following section, the device’s benefits outweigh these risks.  
7.3 
Benefit – Risk Assessment 
The EndoZip™ System is expected to provide significant weight loss outcomes including responder rate, 
defined as ≥5%, of at least 50% at 12 months. In addition, the EndoZip™ System is a minimally invasive 
procedure, a reproducible and easy to use device that can aid the obesity treatment by expanding the 
access and acceptability to a broad population segment. The expected risks associated with the system 
use may require, at most, surgical or endoscopic intervention, thus safety profile meets the low to 
moderate risk.  The EndoZip™ System is designed to minimize these risks. In addition, the company 
applied the relevant special control activities to ensure that the system performs in accordance with its 
performance specifications.  Thus, it is reasonable to conclude that the device’s benefits will outweigh 
its risks.  
8.0 Study Objectives  
8.1 
Primary objectives  
The evaluate the safety and effectiveness of the EndoZip system procedure, followed by lifestyle 
modifications, for weight reduction in obese patients with BMI of 30-40 kg/m2. 
8.2 
Secondary objectives: 
o To evaluate the potential improvement in patients’ conditions. 
o To evaluate the duration related to the EndoZip procedure. 
o To evaluate physicians’ satisfaction related to the EndoZip usability. 
9.0 Study Endpoints  
9.1 
Primary endpoints  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 32 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
32 of 83 
The effectiveness of the EndoZip system will be assessed by the following co-primary endpoints: 
1. Mean percent of total body weight loss (%TBWL) after 12 months. 
2. Percentage of patients with a reduction in %TBWL of at least 5% at 12 months.  
Safety will be characterized through a summary of the incidence of adverse events and serious adverse 
events by relation to study treatment. 
A Data Safety Monitoring Board (DSMB) will review and adjudicate all serious device related and non-
related adverse events and any other events deemed necessary. 
9.2 
Secondary endpoints  
The following secondary endpoints will be evaluated: 
1. Percent of excessive weight loss (%EWL) over 6 and 12 months. 
2. Reduction of weight and waist circumference over 6 and 12 months. 
3. Impact of EndoZip procedure on gastric motility at 6 months. 
4. Changes in Weight-related Quality of Life (IWQOL) Questionnaire scores at 6 and 12 months. 
5. Time analysis including procedure duration, anesthesia duration, patient recovery duration. 
6. Change in comorbid conditions over 12 months evaluated by: 
a. Blood pressure 
b. Glucose, HbA1c 
c. Lipid levels (Total Cholesterol, LDL-C, HDL-C, and triglycerides) 
d. Sleep Apnea test 
7. Physicians’ satisfaction based on a questionnaire 
10.0 Study Design 
This multicenter, prospective, single arm study will include up to 45 patients (10-20 patients per site), 
aimed at evaluating the performance of the EndoZip System in obese patients who failed to reduce 
weight with non-surgical weight-loss methods. 
The first two (2) patients in each site will be considered as run-in period, to compensate for any learning 
curve that may be required for the EndoZip performance evaluation.  
Patients will be enrolled at up to 5 clinical sites in Europe and Israel. Patients who meet the eligibility 
criteria is expected to come the clinic for at least 10 visits.   
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 33 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
33 of 83 
10.1 Study Flow Chart 
 
11.0 Patient Selection and Enrollment 
After being informed of the nature of the study, the patient will sign a written informed consent form 
(ICF) that has been approved by the appropriate Institutional Ethics Committee (IEC) and regional 
Competent Authority (CA). Enrollment of up to 45 patients is planned.  
Patients will be considered for the study if they meet the specific inclusion/exclusion criteria. The 
criteria for enrollment must be followed explicitly. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 34 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
34 of 83 
Enrollment completion is expected to take place up to 6 months following IEC approval of the study. 
11.1 Inclusion Criteria 
1. Age 21-70 
2. BMI ≥ 30 and ≤40 kg/m² 
3. Willingness to comply with the substantial behavioral modifications program as required by the 
procedure 
4. Patients with history of failure with non-surgical weight-loss methods 
5. Willingness to follow protocol requirements, including signed informed consent, routine follow-
up schedule, completing laboratory tests, completing IWQOL questionnaire and completing the 
medically supervised diet and behavior modification program 
6. Residing within a reasonable distance from the investigator's office and able to travel to the 
investigator to complete all routine follow- up visits. 
7. Ability to give informed consent 
8. Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree 
to use adequate birth control methods 
11.2 Exclusion Criteria 
1. Prior surgery of any kind on the gastrointestinal tract (except uncomplicated cholecystectomy or 
appendectomy). 
2. Patients with history of small bowel or colonic obstruction, and/or adhesive peritonitis and/or 
abdominal adhesions. 
3. Patients with any inflammatory disease. 
4. Patients with history of cancer in the gastrointestinal tract. 
5. Potential upper gastrointestinal bleeding conditions such as a history of angioectasias. 
6. A known gastric mass or gastric polyps > 1 cm in size. 
7. Patients with TG >500 or LDL >190. 
8. A known hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or 
intractable gastro-esophageal reflux symptoms while on maximal medical therapy. 
9. A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could 
impede passage of the endoscope. 
10. Patient with motility disorders of the GI tract or intractable constipation. 
11. Patients with known coagulation disorder (INR >1.5) or on anticoagulation therapy. 
12. Type 1 diabetes or Type 2 diabetes with a HgbA1c >8 in 6 weeks prior the procedure or use of any 
medication for diabetes other than metformin. Patients with any serious health condition 
unrelated to their weight that would increase the risk of endoscopy. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 35 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
35 of 83 
13. Patients with chronic abdominal pain 
14. Patients with hepatic insufficiency or cirrhosis 
15. Patients that used an intragastric device for weight loss within 2 years prior to this study. 
16. Patients with psychological health questionnaire-9 (PHQ-9) score of 10 or higher. 
17. Patients receiving daily prescribed treatment with high dose aspirin (> 100mg daily), anti-
inflammatory agents, anticoagulants or other gastric irritants. 
18. Patients with history or current abuse of drugs or alcohol  
19. Patients with known hypersensitivity to Spirulina, egg, milk or wheat allergens (unable to go 
through the GEBT) 
20. Patients who are unable or unwilling to take prescribed proton pump inhibitor medication. 
21. Patients who are pregnant or breast-feeding. 
22. Patients who are taking medications that cause weight loss. 
23. Patients with Severe cardiopulmonary disease or other serious organic disease which might 
include known history of coronary artery disease, Myocardial infarction within the past 12 
months, poorly-controlled hypertension, required use of NSAIDs 
24. Patients taking medications on specified hourly intervals that may be affected by changes to 
gastric emptying, such as anti-seizure or anti-arrhythmic medications. 
25. Patients who are taking corticosteroids, immunosuppressants, and narcotics. 
26. Symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease. 
27. Pre-existing respiratory disease such as chronic obstructive pulmonary disease (severe COPD), 
pneumonia or cancer. 
28. Diagnosis of autoimmune connective tissue disorder (e.g. lupus, HIV, erythematous, scleroderma) 
or immunocompromised 
29. Specific diagnosed genetic disorder such as Prader Willi syndrome (motility disorder). 
30. Eating disorders including night eating syndrome (NES), bulimia, binge eating disorder, or 
compulsive overeating. 
31. Known history of endocrine disorders affecting weight such as uncontrolled hypothyroidism. 
 
11.3 Withdrawal Criteria 
Patients may withdraw from the study at their own request or at the request of their legally acceptable 
representative. The investigator may withdraw a patient from the study at any time for the following 
reasons:  
❖ Severe side effects clearly related to the study device. 
❖ Presence or appearance of exclusion criteria. 
❖ Appearance of accompanying diseases rendering further participation in the study impossible. 
❖ A significant protocol violation, as determined either by the sponsor or the investigator  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 36 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
36 of 83 
❖ Patient noncompliant with investigational procedures 
❖ Patient noncompliant with visits 
❖ At the specific reasonable request of the sponsor 
The sponsor must be informed in each withdrawal case. The reason for withdrawal must be recorded in 
the eCRF and in the patient file. 
11.4 Selection of Investigators and Training 
Certified gastroenterologists will be considered for participation as investigators in this study. Physicians 
in training (residents, fellows) and physician assistants may assist the Study Investigator in any aspect of 
the procedure as per standard procedures and practices at his/her institution. 
Each Investigator participating in the clinical trial and the associated clinical study staff will receive 
training on the clinical protocol. This includes training on AE reporting, electronic Case Report Form 
(eCRF) completion, and Good Clinical Practice (GCP), as well as the device and system (including 
procedural use, device characteristics, shelf life and storage requirements, warnings, and precautions). 
12.0 Study Procedures 
12.1 Clinical Laboratory Investigation 
Samples for hematology, serum chemistry, urinalysis will be analyzed by the local laboratory at 
screening, at the 2, 6 and 12 months after the EndoZip procedure.  
The panels of laboratory tests to be performed are showed below: 
Hematology: red blood cells (RBC) and parameters (Hemoglobin, hematocrit) and reticulocyte count, 
white blood cells (WBC) and differential and platelets count. 
• 
PTT, PT and INR   will be done only at the screening visit.   
Comprehensive Metabolic Panel (CMP) and urine analysis :Blood glucose, HbA1c, Calcium, Albumin, 
Total protein, Sodium, Potassium, Total CO2,Chloride,ALP,ALT,AST,Bilirubin. 
Urinalysis: Performed locally on freshly voided clean sample by dipstick for protein, glucose, blood, pH 
and ketones. If the dipstick finding are abnormal based on the provided Lab values or investigator's 
judgment, then a microscopic evaluation will be performed to assess the abnormal findings.  
Lipid screen battery including Cholesterol level, HDL, LDL and Triglycerides.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 37 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
37 of 83 
In addition, the following tests will be performed to evaluate patient health condition. Theses test will 
be done only at the screening and at EndoZip procedure. 
Endocrinology: a quantitative β-HCG blood test (R/o Pregnancy).  
12- lead electrocardiogram (ECG): The test will be performed at screening, and at EndoZip procedure 
day. The following will be measured or calculated: Heart rate, PR, QSR, QT, QTc and rhythm. The 
investigator or qualified designee will review the ECG locally and asses the results as normal or abnormal 
(clinically significant or not clinically significant). 
12.2 Physical Examination and Vital Signs 
Physical examination will include an assessment of all the major body systems.  
Vital signs will include blood pressure, heart rate, pulse and body temperature and will be taken in 
supine position after the patient has been resting for at least 5 minutes.  
Physical examination and vital signs will be taken at all in-person visits during the study. The results will 
be documented in the eCRF. 
12.3 Body Height, Weight and Waist Circumference  
Height, Weight and Waist Circumference will be measured at all in-person visits. The results will be 
documented in the eCRF. 
Waist Circumference Measuring instructions: 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 38 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
38 of 83 
To measure the waist, place a flexible tape measure 
between your bottom rib and your hip bone. The tape 
measure should be approximately in line with your belly 
button. 
Take your waist measurement on a normal breath out 
Don’t pull or tuck in your stomach 
Ensure the tape measure is level at the front and the back 
of your body 
 
The tension of the tape should be such that the tape is held against the skin but not so tight as to 
cause an indentation in the skin 
 
12.4 Endoscopy Procedure  
EndozipTM procedure is performed with concurrent endoscopy. The procedure will be done for safety 
and efficacy purposes. The stitches will be evaluated with respect to the order that they were applied 
per stomach location and their durability.  Evaluated will be done via the endoscopy performed. 
Endoscopy procedure will be performed at visit 4 (2 months after the procedure) and at visit 6 (6 
months after the procedure).  The results will be documented in the eCRF. 
12.5 Assessment of Adherence 
Patients will be instructed to follow post-procedure diet and physical activities, per Appendix A. Patients 
will be asked to record and provide their diet and their physical activities in the provided diary log at 
time of their scheduled follow-up visits (Diary log is provided in appendix C). Patients adherence to the 
instructed regime will be assessed in all follow-up visits. Adherence to the regime will be documented in 
the eCRF. 
12.6 Quality of Life influence and Phycological Health Questionnaire 
Quality of Life influence will be evaluated via IWQOL questionnaire, filled-out by the patients at 
screening, and at 2, 6 and 12 months after the procedure.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 39 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
39 of 83 
Physiological health will be evaluated via PH-9 questionnaire, filled-out by the patients at screening visit 
and will support the patients’ eligibility to the study.  
The questionnaires will serve as source documents and will be transcribed into the study eCRF by 
Investigators or their designees. 
12.7 Home Sleep Apnea Test (HSTS) 
The test will be performed only for patients suffering from diagnosed obstructive sleep apnea. It will 
take place prior to the procedure, 2, 6 and 12 months after the procedure. 
Obstructive sleep apnea (OSA) in this study is considered as a comorbidity if the  hypopnea index, AHI, ≤ 
15 events/hour. The purpose of the test is to evaluate if there is any improvement due to the EndozipTM 
procedure.  
The following parameters will be measured:  
1. Respiratory airflow 
2. Respiratory effort  
3. Oxygen saturation. 
These parameters will be collected by the WatchPAT 200 (ITAMAR Medical –Israel) which is an FDA-
approved portable diagnostic device that uniquely uses finger based physiology and innovative 
technology to enable simple and accurate Obstructive Sleep Apnea (OSA) testing. 
For further instructions and guide: https://www.youtube.com/watch?v=JqZczOBcVdk 
 
 
 
 
 
12.8 Gastric Emptying Breath Test (GEBT) 
The Gastric Emptying Breath Test (GEBT), to be used with the GEBT test meal, is intended for use in 
the measurement of the rate of gastric emptying of solids and as an aid in the diagnosis of delayed 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 40 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
40 of 83 
gastric emptying. The test will be performed for all patients prior to the EndozipTM procedure and 6 
months after the procedure. 
GEBT is a non-radioactive test that utilizes carbon-13 (13C). Labeling with 13C stable isotope is 
essentially safe, as 1.1% of our bodies, and of the food we eat, consists of 13C; the remaining 98.9% 
consists of 12C. The GEBT measures the rate of gastric emptying of solids and aids in the diagnosis of 
gastroparesis. The test system utilizes a gas 
isotope ratio mass spectrometer for the 
measurement of the ratio of 13CO2 to 12CO2 in 
breath samples. In a clinical trial comparing the 
GEBT and scintigraphy, the GEBT was shown to 
be comparable to scintigraphy. The GEBT is 
shown in Figure 2.  
 
Contraindications to use of the GEBT: 
• 
Individuals with known hypersensitivity to 
Spirulina, egg, milk or wheat allergens should 
avoid the GEBT. 
• 
Because the GEBT is an indirect multi-
compartmental method of measuring gastric 
emptying, GEBT results may be inaccurate in 
individuals compromised with significant small 
bowel, pancreatic, liver and/or lung disease. 
Consequently, GEBT should not be administered 
to patients with pulmonary dysfunction (e.g. 
COPD) and/or small bowel malabsorption. 
 
The GEBT procedure flow chart is presented in Figure 3. 
 
 
 
Figure 2 - GEBT kit for gastric emptying testing 
Figure 3 – GEBT Procedure Flow chart 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 41 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
41 of 83 
12.1 Usability Assessment 
Usability will be evaluated by a questionnaire. The physicians who will conduct the EndoZip procedure 
will fill-out a dedicated questionnaire specified in Appendix B. The Physician feedback will be 
documented in the eCRF. 
13.0 Study Schedule and Activities 
13.1 Visit 1 - Screening and Informed Consent  
A screening/baseline will be performed prior to the scheduled EndoZip procedure to assess preoperative 
eligibility. The patient clinical assessment includes few tests, thus it may be done in few days. 
At the screening visit, patients will be approached to obtain written informed consent prior to any study 
specific procedures being performed. The purpose of the study and the benefits and risks of the 
procedures will be explained to the patient and the consent process must be documented accordingly in 
the medical record. Patients who agree to study participation must sign an IEC-approved ICF. Patients 
will be informed that their participation in this study is voluntary and they may refuse to participate or 
discontinue from the study at any time. Patients will be given the opportunity to ask the investigator 
questions so that they are adequately informed about the research. A copy of the signed informed 
consent must be provided to the patient and the informed consent process will be documented in 
source documents. 
If new information becomes available that may affect a patient’s decision to continue to take part in the 
study, this information will be discussed with the patient by the investigator. 
An identifier will be assigned to each participant signing the informed consent form. This identifier will 
be assigned manually, in a sequential order, in the eCRF. Numbers of patients whose participation in the 
study is terminated prior to procedure may not be reassigned. 
All patients that are considered to have comorbidities must have definite diagnosis previously to the 
screening visit (by blood tests and/or imaging). 
The following assessments will be performed prior to the scheduled procedure and the results recorded 
on the appropriate patient eCRFs: Verification of eligibility Criteria: 
• 
Assessment of demography characteristics 
• 
Assessment of surgical and medical history (prior abdominal surgery, GI symptoms), Obesity 
History 
• 
Assessment of general medical history including use of concomitant medication 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 42 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
42 of 83 
• 
Patient clinical condition will be assessed based on the followings: 
o Physical examination 
o Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) 
o Waist circumference, Height, Weight 
o Laboratory evaluations (Hematology, CBC with differential, PTT, PT and INR, Comprehensive 
Metabolic Panel (Kidney and liver functions – blood glucose, HbA1c, Urinalysis, TSH, fasting 
lipid panel) 
o Gastric Emptying Breath Test (GEBT) 
o Weight on Quality of Life (IWQOL) questionnaire  
o Psychological health questionnaire-9 (PHQ-9)  
o Patients with diagnosed Sleep Apnea disorder will undergo HSAT (home sleep apnea 
testing). 
13.1.1 Recruitment visit: 
Patients who are eligible for the study will be invited to participate in the study.  
Patients who were found to be not eligible for the study following signature of the Informed 
Consent Form will be withdrawn from the study.  
13.1.2 Screen Failures 
A patient is considered enrolled in the study when the ICF is signed. Only patients who receive 
study-assigned procedures will be followed. Patients who provide study consent, but then are 
determined to be ineligible will be considered screening failures and will not require additional 
study follow-up. The reason for the screening failure will be clearly documented, the Patient 
“Enrollment and Visit Log” will be completed and the patient eligibility section in visit 1 as well as a 
"Study Completion" form will be completed in the eCRF.  
13.2 Randomization 
NA –Single study arm 
13.3 Visit 2 - EndoZip Procedure Day  
The patients will undergo the EndoZip procedure within 30 days after signing the Informed Consent 
Form (ICF).  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 43 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
43 of 83 
Pre-Examination Procedures: 
• 
Verify the informed consent was obtained after explaining all risks, benefits, and 
alternatives to the candidate. 
• 
Verify all Laboratory results were documented. 
• 
Verify the GEBT results were documented. 
• 
Verify the Quality of life (IWQOL) and Psychological health (PHQ-9) questionnaires were 
documented. 
• 
For patients who suffer from Sleep Apnea, verify the Sleep Apnea test results were 
documented. 
• 
Verify the patient eligibility. 
• 
Verify all background/clinical information, demographic and medical history was 
documented. 
In addition the patients will undergo / repeat the following test prior the EndoZip procedure: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured. Note: if blood pressure measurement > 160/100 it is 
recommended not to perform the EndoZip procedure.  
• 
Weight, Height, Waist circumference will be measured. 
• 
ECG test 
• 
Female patients, pregnancy test 
• 
Endoscopy screening procedure to R/O any findings in the upper GI tract. 
EndoZip Procedure 
The EndoZip procedure will be performed by the clinical investigator(s), experienced in endoscopic 
suturing devices according to local standard of care. Physicians in training (residents, fellows) and 
physician assistants may assist the Study Investigator in any aspect of this part of the procedure as per 
standard procedures and practices at his/her institution. Anesthesia will be applied as well per the 
standard of care. In order to ensure correct operation of the EndoZip System a NiTiNotes representative 
may attend the procedure.  Using the EndoZip system, will followed by specific training with the device 
that will be provided by the sponsor prior to the study. EndoZip System operation is described in the 
Instruction for Use.   
Once the procedure is completed, relevant data will be documented in the Electronic Case Report Form 
(eCRF) in addition, findings, diagnosis as well as physician’s useability and satisfaction questionnaire will 
be recorded/completed.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 44 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
44 of 83 
The EndoZip procedure will be recorded on digital media via the endoscope equipment used during the 
procedure. Only the patient study ID and initials should appear in the recorded video. 
All endoscopy still pictures will be saved in a digital format. Quality copies of the pictures taken during 
endoscopy will be provided to the sponsor. 
These videos and pictures will be archived and may be used in future analyses to, for example, provide 
further information about observed sutures applied during the EndoZip procedure. 
Any AE will be documented in the eCRF. 
Post-Examination  
Patients will be transferred to recovery room for observation per standard endoscopic suturing standard 
of care.   
Standard post endoscopic suturing care is required to achieve optimal results. The study post-procedural 
guidance includingdiet protocol and physical activities is provided in Appendix A. Lifestyle modification 
will be provided by a dietitians/nutritionists.   
Follow-up call will be conducted 1-2 working days after patients’ discharge to verify that there has been 
no change in patients well-being. Any AE will be documented in the eCRF. 
13.4 Visit 3 – Follow Up 1 Week Post Procedure (7-10 days after patient discharge) 
The following activities will be performed and documented at this visit: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured  
• 
Weight, Height, Waist circumference will be measured. 
• 
Patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  
• 
Any adverse event experienced by patient since last visit will be recorded. 
The relevant data will be documented in the eCRF. 
13.5 Visit 4 – Follow Up 1-month Post Procedure 
This visit will be conducted 1 month (±1week) after the procedure.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 45 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
45 of 83 
The following activities will be performed and documented at this visit: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured  
• 
Weight, Height, Waist circumference will be measured. 
• 
Patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  
• 
Concomitant medication will be recorded including any changed from the last visit. 
• 
Any adverse event experienced by patient since last visit will be recorded. 
The relevant data will be documented in the eCRF. 
13.6 Visit 5 – Follow Up 2 months Post Procedure  
This visit will be conducted 2 months (±1week) after the procedure.  
The following activities will be performed and documented at this visit: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured  
• 
Weight, Height, Waist circumference will be measured. 
• 
Laboratory evaluations – Hematology, - CBC with differential, Comprehensive Metabolic 
Panel Kidney and liver functions – blood glucose, HbA1c, Urinalysis, lipid profile. 
• 
Endoscopy procedure to inspect the stomach stitches. 
• 
Patients will require to fill-out the IWQOL questionnaire 
• 
Patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  
• 
Concomitant medication will be recorded including any changed from the last visit. 
• 
Any adverse event experienced by patient since last visit will be recorded. 
• 
Patients with diagnosed Sleep Apnea disorder will undergo HSAT (home sleep apnea 
testing). 
The relevant data will be documented in the eCRF. 
13.7 Visit 6 – Follow Up 6 months Post Procedure  
This visit will be conducted 6 months (±1week) after the procedure.  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 46 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
46 of 83 
The following activities will be performed and documented at this visit: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured  
• 
Weight, Height, Waist circumference will be measured. 
• 
Laboratory evaluations – Hematology, - CBC with differential, Comprehensive Metabolic 
Panel Kidney and liver functions – blood glucose, HbA1c, Urinalysis, lipid profile. 
• 
Endoscopy procedure to inspect the stomach stitches. 
• 
Patients will require to fill-out the IWQOL questionnaire 
• 
Patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  
• 
Gastric Emptying Breath Test (GEBT) 
• 
Concomitant medication will be recorded including any changed from the last visit. 
• 
Any adverse event experienced by patient since last visit will be recorded. 
• 
Patients with diagnosed Sleep Apnea disorder will undergo HSAT (home sleep apnea 
testing). 
 
The relevant data will be documented in the eCRF. 
13.8 Visit 7 – Follow Up 12 months Post Procedure  
This visit will be conducted 12 months (±1week) after the procedure.  
The following activities will be performed and documented at this visit: 
• 
Physical examination 
• 
Vital signs (blood pressure and heart rate - supine, pulse, body temperature, respiratory rate 
(RR) and SpO2) will be measured  
• 
Weight, Height, Waist circumference will be measured. 
• 
Laboratory evaluations – Hematology, - CBC with differential, Comprehensive Metabolic 
Panel Kidney and liver functions – blood glucose, HbA1c, Urinalysis, TSH, lipid profile. 
• 
Patients with diagnosed Sleep Apnea disorder will undergo HSAT (home sleep apnea 
testing). 
• 
Patients will require to fill-out the IWQOL questionnaire 
• 
Patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  
• 
Concomitant medication will be recorded including any changed from the last visit. 
• 
Any adverse event experienced by patient since last visit will be recorded. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 47 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
47 of 83 
The relevant data will be documented in the eCRF. 
13.9 Additional Follow Ups  
Additional Visits 
Patients will receive brief (30min) telephone calls in the months that do not include in person visits (in 
months 3, 5, 7, 9, and 11 after the procedure). These counseling sessions are primarily designed to 
improve adherence to recommendations to consume a healthy diet and increase physical activity to 
promote weight loss and overall health.  
Additional In Person Visits 
In addition to the visits above, patients will visit the clinic in 4, 8 and 10 months after the procedures. In 
these visits, patients will meet with dietitians/nutritionists where he/she will be queried regarding their 
adherence to the post-procedure diet protocol and reminded to follow the instructions.  These 
counseling sessions are primarily designed to improve adherence to recommendations to consume a 
healthy diet and increase physical activity to promote weight loss and overall health. 
Before a patient is considered “lost to follow-up”, there must be at least three (3) documented attempts 
to contact the patients. 
 

 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 48 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
48 of 83 
13.10 Schedule of Events 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Additional In-
Person Vits 
Parameters 
Screening 
Procedure Day 
(30 days after 
ICF) 
1 week (7-10 
days) after the 
discharge 
1 month (±1wk) 
after the 
procedure 
2 months 
(±1wk)  after 
the procedure 
6 months 
(±1wk)  after 
the procedure 
12 months 
(±1wk)  after 
the procedure 
At 4,8,10 
months after 
the procedure 
Informed consent 
x 
 
 
 
 
 
 
 
Eligibility criteria 
x 
 
 
 
 
 
 
 
Demographic 
data 
x 
 
 
 
 
 
 
 
Medical history & 
concomitant 
medication 
x 
 
x 
x 
x 
x 
x 
x 
Diet & physical 
activity 
adherence 
 
x 
x 
x 
x 
x 
x 
x 

 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 49 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
49 of 83 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Additional In-
Person Vits 
Parameters 
Screening 
Procedure Day 
(30 days after 
ICF) 
1 week (7-10 
days) after the 
discharge 
1 month (±1wk) 
after the 
procedure 
2 months 
(±1wk)  after 
the procedure 
6 months 
(±1wk)  after 
the procedure 
12 months 
(±1wk)  after 
the procedure 
At 4,8,10 
months after 
the procedure 
Weight, Height, 
Waist 
circumference  
x 
x 
x 
x 
x 
x 
x 
x 
Physical 
examination and 
Vital signs 
x 
x 
x 
x 
x 
x 
x 
x 
Laboratory tests 
x 
 
 
 
x 
x 
x 
 
Electrocardiogra
m (ECG) test 
 
x 
 
 
 
 
 
 
Gastric Emptying 
Breath Test 
(GEBT) 
x  
 
 
 
 
x 
 
 

 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 50 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
50 of 83 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Additional In-
Person Vits 
Parameters 
Screening 
Procedure Day 
(30 days after 
ICF) 
1 week (7-10 
days) after the 
discharge 
1 month (±1wk) 
after the 
procedure 
2 months 
(±1wk)  after 
the procedure 
6 months 
(±1wk)  after 
the procedure 
12 months 
(±1wk)  after 
the procedure 
At 4,8,10 
months after 
the procedure 
Pregnancy Test 
 
x 
 
 
 
 
 
 
Quality of life 
questionnaire 
(IWQOL) 
x 
 
 
 
x 
x 
x 
 
Psychological 
health 
questionnaire 
(PHQ-9) 
x 
 
 
 
 
 
 
 
Sleep Apnea test 
(HSTs) 
x 
 
 
 
x 
x 
x 
 
EndoZipTM 
Procedure 
 
x 
 
 
 
 
 
 

 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 51 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
51 of 83 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Additional In-
Person Vits 
Parameters 
Screening 
Procedure Day 
(30 days after 
ICF) 
1 week (7-10 
days) after the 
discharge 
1 month (±1wk) 
after the 
procedure 
2 months 
(±1wk)  after 
the procedure 
6 months 
(±1wk)  after 
the procedure 
12 months 
(±1wk)  after 
the procedure 
At 4,8,10 
months after 
the procedure 
Usability 
Questionnaire 
 
x 
 
 
 
 
 
 
Endoscopy 
Procedure 
 
x 
 
 
x 
x 
 
 
AEs and SAEs1 
 
x 
x 
x 
x 
x 
x 
x 
 
1 Adverse events will be monitored continuously until the end of the study period. AEs that are still unresolved at the last study visit will be followed for outcome 
information until resolution or stabilization of the event for a continuous period of 2 weeks, whichever occurs first. Unresolved SAEs will be followed until resolved. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 52 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
52 of 83 
13.11 Required Concomitant Medications or Therapies 
13.11.1 Concomitant Medications, Treatments, and Procedure 
All concomitant prescription medications taken by the patient will be recorded as prior medications 
during screening and concomitant medications taken during study participation will be recorded on 
the electronic case report forms (eCRFs). Assessment of eligibility will include a review of permitted 
and prohibited medications. For details, refer to eligibility criteria. 
For this protocol, a prescription medication is defined as a medication that can be prescribed only by 
a properly authorized/licensed clinician. Medications to be reported in the eCRF are concomitant 
prescription medications, over-the-counter medications and non-prescription medications. 
13.11.2  Reduce Medications, Treatments, and Procedure 
Use of non-investigational medicinal products 
Prophylactic topical and/or systemic antibiotic agents may be prescribed by Investigators, as rescue 
(or escape) medication to alleviate the anticipated adverse reactions. This may be done per 
recommendations in the post-procedural guidance, i.e. the post-procedural protocol used by the 
multidisciplinary team, or per routine local practice. NOTE: Such medication will be recorded as a 
concomitant medication in the appropriate study eCRF. Dose, duration and frequency will be in 
accordance with local practice. No special arrangements for the prescribing practices are provided in 
this protocol. These medicinal products do not fall within the definition of investigational medicinal 
products in Directive 2001/20/EC and can be referred to as NIMPs. 
14.0 Statistical Analysis  
14.1 Sample Size Determination 
This is a pilot study that will include up to 45 patients; no statistical considerations were made to 
determine the sample size. 
The first two (2) patients per site will be considered as run-in period, to compensate for any learning 
curve that may be required for the EndoZip performance evaluation.  
Safety evaluation will include all enrolled patients. 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 53 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
53 of 83 
14.2 Description of statistical methods 
14.2.1 Analysis of Populations 
Full Analysis Set (FA): includes all enrolled patients who undergone EndoZip procedure, excluding 
patients who enrolled in the run-in period. 
Modified Full Analysis Set (mFA): The modified full (mFA) analysis set will include all patients who have 
at least one post initiation follow up visit and met the study Eligibility Criteria, and enrolled after the 
run-in period. 
Per-Protocol (PP) analysis set: includes all patients from the mFA set who do not have any major 
protocol violations, and enrolled after the run-in period, and enrolled after the run-in period. 
Statistical Analysis of Analysis Sets: Safety assessments will be performed on all enrolled patients set. 
The mFA will serve as the principal data analysis set for the primary and secondary statistical efficacy 
endpoints.  The primary, secondary efficacy assessment will also be performed on the  PP and FA 
cohorts  for descriptive purposes and to show consistency of study results. 
14.2.2 General Methods: 
Statistical analyses will be mainly descriptive in nature. Any statistical tests if performed will be two-
sided, unless otherwise stated. 
Any deviation from specified statistical plan will be in addition to “per protocol” analysis and will be 
reported as such Post-hoc analysis will be conducted according to the existing data gathered, if 
necessary. 
14.2.3 Handling of the Type I Error  
The overall significance level for this study is 5%, confidence intervals will be two-sided using a 95% 
confidence level, except for treatment by site interaction that will be tested at a significance level of 
10%. 
Study data will be summarized with descriptive statistics and presented in tables and figures. 
Continuous variables will be summarized by a mean, standard deviation, minimum, median and 
maximum and categorical variables by a count and percentage. If multiple measurements are taken 
in a single patient, statistics described below will be appropriately modified to accommodate the 
within patient correlation. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 54 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
54 of 83 
14.3 Demographic, Medical history, and Baseline characteristics 
Basic demographic and baseline characteristics will be collected during the screening visit. In addition to 
the evaluation of the patient's medical history in terms of study eligibility, all relevant medical conditions 
will be documented on the appropriate eCRF. 
The patient's entire obesity history will be collected on the appropriate eCRF including previous 
treatments, medications and interventions done to lose weight. 
Events that occur after signing of informed consent but prior to the EndozipTM procedure, unless serious 
and due to protocol – mandated procedure, should be recorded on the Medical History eCRF. 
14.4 Primary Endpoint Analysis 
The %TBWL at each visit will be calculated as 100*(Weight(BL) -Weight(Visit))/ Weight(BL), where weight 
is measured in kilograms. %TBWL will be summarized with descriptive statistics at each follow-up visit. 
%TBWL will be evaluated by using repeated measures analysis of covariance (ANCOVA MIXED model). 
Baseline weight, center and visit will be used as covariates. Baseline weight will be entered as a continuous 
variable so that the potential for co-linearity problems will be minimized.  
The unstructured covariance matrix structure will be used. If the model doesn’t converge, then either the 
compound symmetry or autoregressive (whichever model has the lower AIC statistic) covariance matrix 
structure will be used instead. For this evaluation no imputation of missing data is considered beyond the 
model estimates.  
The model estimated mean %TBWL at each visit will be presented with 95% confidence interval and level 
of significance. 
A count and percentage of patients achieving at least 5% TBWL will be presented with exact 95% 
confidence interval.  
 
14.4.1 Subset Analysis of the primary endpoint: 
Additionally, the %TBWL median, mean and standard deviation and percent of patients with greater 
than 5%TBWL will be summarized. Covariates may include demographic data (sex, age, BMI) or other 
baseline characteristics.  
14.5 Safety Analysis 
The cumulative incidence of adverse events observed during the procedure and throughout the follow-
up period, will be presented in tabular format. A detailed list of all adverse events will be presented. The 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 55 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
55 of 83 
adverse event rate will be compiled with respect to seriousness, severity, expectedness and relationship 
to procedure and device. In addition, listings of all safety measures will be produced. 
14.6 Secondary Endpoints Analysis 
The percent excess weight loss (%EWL) will be calculated as (Weight(BL) – Weight(Visit)/ 
ExcessWeight(BL), where ExcessWeight(BL) is calculated as difference between the patient’s baseline 
weight in kilograms and the kilograms at which the patient’s BMI would be 25. 
 
 
 
Change from baseline in BMI at 1, 2, 6 and 12 month(s) by study group will be summarized with descriptive 
statistics with 95% confidence intervals. 
 
  
 
IWQOL questionnaire records will be summarized by study groups will be summarized with descriptive 
statistics with 95% confidence intervals. 
 
Time analysis  
Time analysis including procedure duration, anesthesia duration, patient recovery duration will be 
evaluated and will be summarized with descriptive statistics with 95% confidence intervals. 
 
Change in Comorbid Conditions  
Clinically significant changes at 6 and 12 months in fasting plasma glucose and HbA1c concentrations, 
change in systolic and diastolic blood pressure, changes in plasma total cholesterol, low-density 
lipoprotein cholesterol and triglyceride concentrations, will be evaluated and will be summarized with 
descriptive statistics with 95% confidence intervals 
Percentage of patients who had clinically significant change will be provided with 95% confidence interval. 
 
Usability and Physicians’ satisfaction  
Physicians’ satisfaction will be evaluated by a questionnaire will be summarized with descriptive statistics 
with 95% confidence intervals. 
Excess Weight Loss % (EWL%) 
EWL% of patients at 1, 2, 6 and 12 month(s) by study group will be summarized with descriptive statistics 
with 95% confidence intervals. 
Change of Weight and Waist Circumference Over 12 Months from Baseline  
Changes in Weight-related Quality of Life (IWQOL) Questionnaire at 12 months  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 56 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
56 of 83 
The physicians will be asked to fill-in a dedicated questionnaire to include their feedback on the 
procedure. 
14.7 Interim Analyses 
An interim analysis is planned after enrollment of 25 patients undergone at least 2 months of follow up 
aims to verify the recruitment pace and patients’ adherence to the study flow.  
 
15.0  Adverse Events (AEs) and Complications 
AE and AE subcategories are defined per ISO14155:2020, as described below. 
15.1 Adverse Event (AE) 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in patients, user or other person, whether or not related to the 
investigational medical device and whether anticipated or unanticipated.  
This definition includes events related to the investigational medical device or the comparator and the 
procedures involved. For users or other persons, this definition is restricted to events related to the use 
of investigational medical devices or comparators.   
AEs will be collected starting from the time patient is enrolled until the follow-up period is completed. 
15.2 Serious Adverse Event (SAE) 
A Serious AE (SAE) is an AE that led to any of the following 
a) Death, 
b) Serious deterioration in the health of the patient, users, or other persons as defined by one or more 
of the following: 
1) A life-threatening illness or injury, or 
2) A permanent impairment of a body structure or a body function including chronic disease, or 
3) In-patient or prolonged hospitalization, or 
4) Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the clinical 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 57 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
57 of 83 
investigational plan, without serious deterioration in health, is not considered a SAE. 
15.3 Serious Health Threat 
Some important medical events, although they may not result in death, be life-threatening, or require 
hospitalization may still be considered SAEs. Life threatening means that the patient, users or other 
persons, was at imminent risk of death or a serious deterioration in the health, and that requires prompt 
remedial action, medical or surgical intervention, for other patients, users or other persons to prevent 
one of the outcomes listed above. 
This would include events that are of significant and unexpected nature such that they become alarming 
as a potential serious health hazard or possibility of multiple deaths occurring at short intervals. 
15.4 Adverse Device Effect (ADE) 
An Adverse Device Effect (ADE) is an AE related to the use of an investigational medical device.  
This definition includes AEs resulting from insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the investigational medical device. 
This definition includes any event resulting from use error or from intentional misuse of the investigational 
medical device. 
15.5 Serious Adverse Device Effect (SADE)  
A Serious Adverse Device Effect is an adverse device effect that has resulted in any of the consequences 
characteristic of an SAE. 
15.6 Unanticipated Serious Adverse Device Effect (USADE) 
An Unanticipated Serious Adverse Device Effect is a serious adverse device effect which by its nature, 
incidence, severity, or outcome has not been identified in the current risk assessment.  
15.7 Adverse Event Severity Classification 
Mild 
Awareness of event, but easily tolerated 
Moderate 
Discomfort enough to cause some interference with activities of daily living (ADL); 
Minimal local or noninvasive intervention indicated. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 58 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
58 of 83 
 Severity will be defined according to the following criteria: 
NOTE: An AE can be classified as severe and not deemed a SAE. Similarly, a SAE is not automatically severe 
in nature. 
* Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
15.8 Adverse Event Relationship Classification 
Relationship to study product administration will be determined as follows: 
• 
No Relationship: No relationship between the AE and the administration of study treatment 
and a known relationship to other etiologies such as concomitant medications, procedure, or 
patient’s clinical state. 
• 
Possible Relationship: An AE that follows a reasonable temporal sequence from administration 
of the study treatment and follows a known response pattern to the study treatment but could 
have been produced by the participant’s clinical state or by other therapies. 
• 
Probable Relationship: An AE that follows a reasonable temporal sequence from administration 
of the study treatment; follows a known response pattern to the study treatment; and cannot 
be reasonably explained by the known characteristics of the participant’s clinical state or by 
other therapies. 
• 
Definite Relationship: An AE that follows a plausible temporal sequence from administration of 
the study treatment and follows a known response pattern to the study treatment. The 
reaction cannot be reasonably explained by the known characteristics of the patient’s clinical 
state or other modes of therapy administered to the patient. 
• 
Unknown/Impossible to Determine: Given the information available, sequence and timing of 
events, it is unknown or impossible to determine the relationship of the AE with the study 
treatment. 
15.9 Adverse Event Outcome Classification 
Outcome of the event will be defined according to the following:  
• 
Resolved: The event has fully resolved at the end of the study. 
Severe 
Hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL* 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 59 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
59 of 83 
• 
Resolved with sequelae: The event has resolved, but retained pathological conditions resulting 
from the prior disease or injury. 
• 
Continuing: The event is ongoing at the end of the study. 
• 
Death: This event is determined to be the cause of death. 
 
15.10 Device Deficiencies 
A device deficiency is an inadequacy of a medical device related to its identity, quality, durability, 
reliability, safety, or performance, such as malfunction, misuse or use error and inadequate labeling. 
All device deficiencies will be documented, and the device should be returned to NiTiNotes for analysis, if 
possible. Instructions for returning the investigational device will be provided. Device deficiencies should 
also be documented in the patient’s medical record. 
Device deficiencies are NOT to be reported as AEs. However, if there is an AE that results from a device 
deficiency, that specific event would be recorded on the appropriate eCRF. 
15.11 Adverse Event Recording and Reporting 
Assessment of the occurrence of an AE will be based on changes in the patient’s signs and symptoms. AEs 
will be monitored until a patient completes the study unless the Investigator determines the event is 
related to the investigational device, in which case they will be monitored until resolution if possible. 
Medical care will be provided, as defined in the informed consent, for any AE related to study 
participation. AEs will be collected on an AE eCRF and applicable source documentation.  
The following should not be considered an AE: 
• 
A condition requiring a preplanned procedure unless the condition worsened since screening 
• 
A preexisting condition found as a result of screening, unless the condition has worsened since 
enrollment. 
All AEs observed during the course of this study, regardless of severity or relationship to the 
investigational device will be recorded on the appropriate eCRF. 
15.11.1 Data Safety and Monitoring Board (DSMB) 
An independent group of experts chosen by the sponsor will constitute the Data and Safety 
Monitoring Board (DSMB). The DSMB will review and adjudicate all serious device related and non-
related adverse events and any other events deemed necessary. The Adverse Events will be reported 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 60 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
60 of 83 
as per the standard clinical practices. All adverse event incidence rates will be summarized by 
anticipation, severity and relationship to the investigational device. 
The incidence of major complications using the EndoZip system will be presented.  
15.12 Reporting Responsibilities 
Throughout the course of the study, all efforts will be made to capture and evaluate adverse events. If an 
adverse event occurs, the first concern is for the safety and welfare of the patient. Appropriate medical 
intervention will be made. All adverse events observed by the Investigator or reported by the patient, 
whether or not related to the EndoZip system or to a study-procedure, have to be recorded in the 
appropriate section of the patient’s eCRF. eCRFs will be captured and monitored throughout the study. 
Information about AEs will include as a minimum the description of the event, date of onset, date the 
event was noticed by Investigator, an evaluation of the relatedness of the adverse event to the EndoZip 
system and /or study procedure, medical assessment for seriousness, actions taken and whether study 
participation was discontinued.  
A pre-existing condition, which is a condition that is present at the beginning of the study, should be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during 
the study period. 
All Adverse Events still on-going at the end of the study period need to be followed until resolution. 
Serious Adverse Events will be reported by the Investigator to the sponsor with no delay, and no later 
than 2 days after the Investigator learned about the event. The Investigator will use the study specific 
eCRF reporting form. SAEs will be processed and reported by Sponsor to Competent Authorities and 
Ethics Committees according to the applicable local regulations. Serious adverse events that are still on-
going at the end of the study period must be followed up to determine the final outcome. 
The investigator is responsible for the classification of adverse events and together with the sponsor for 
the ongoing safety evaluation of the clinical investigation. The sponsor shall: 
• 
Forward all AE records and the investigator's assessment to the DSMB. The DSMB will fulfill its 
responsibility to monitor the safety of patients by conducting formal reviews of the accumulated 
safety data. These reviews will normally occur at regular intervals, however, in case of specific 
concerns, ad-hoc meetings can be set up. 
A DSMB will evaluate the AE for their relatedness to the investigational device and will make 
recommendation regarding reporting, continuation, modification, or termination of the trial. The 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 61 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
61 of 83 
DSMB will determine and document in writing their seriousness and relationship to the 
investigational device. 
• 
Review all device deficiencies and determine and document in writing whether they could have 
led to a serious adverse device effect;  
• 
Report or ensure the reporting, to the IEC  by the principal investigator(s), of all serious adverse 
events and device deficiencies that could have led to a serious adverse device effect, if required 
by national regulations or by the IEC . The investigator must inform the sponsor and the local IEC  
about any serious adverse effects and serious adverse device effects as soon as becoming aware 
of the occurrence by Fax/Telephone. 
• 
Report to regulatory authorities, within the required time period, all serious adverse events and 
device deficiencies that could have led to a serious adverse device effect, if required by national 
regulations 
• 
Inform all principal investigators in writing of all the serious adverse events at all investigation 
sites that have been reported to the sponsor, and ensure that they are reported to their IEC , if 
required by national regulations; this information shall be sent to all the principal investigators 
within a time frame established based on the perceived risk as defined in the risk analysis report 
• 
Ensure that the IEC and the regulatory authorities are informed of significant new information 
about the clinical investigation.  
• 
In case of serious adverse device effects and device deficiencies that could have led to serious 
adverse device effects, determine whether the risk analysis needs to be updated and assess 
whether corrective or preventive action is required. 
16.0 Ethics and Compliance 
16.1 Statement of Compliance 
This clinical investigation will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki, ISO 14155:2020 (Clinical Investigation of Medical Devices for Human 
Patients – Good Clinical Practice), ICH-GCP, and any regional or national regulations, as appropriate. 
This may include an inspection by NiTiNotes representatives and/or Regulatory Authority 
representatives at any time. The investigator must agree to the inspection of study-related records by 
the Regulatory Authority/ NiTiNotes representatives and must allow direct access to source documents 
to the Regulatory Authority/ NiTiNotes representatives. Regulatory Authority 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 62 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
62 of 83 
approvals/authorizations/notifications, where required, will also be in place and fully documented prior 
to study start. 
16.2 Protocol Compliance 
No changes to the protocol will be permitted without the written approval from NiTiNotes and the IEC. 
The investigator must notify NiTiNotes and the reviewing IEC of any deviation from the Investigational 
Plan when specific to the protection of the life or physical well-being of a patient in an emergency. Such 
notice must be given as soon as possible, but in no event later than 5 working days after the emergency 
has occurred. Except in such an emergency, prior written approval by NiTiNotes is required for changes 
in or deviations from the Plan. If these changes or deviations affect the scientific soundness of the Plan 
or the rights, safety, or welfare of human patients the IEC will also be notified. All other deviations will 
be reported per the site’s IEC deviation policy. Should any deviations from the Investigational Plan occur, 
these will be reviewed by NiTiNotes for their clinical significance. If the event is performed without 
written approval from all parties, the investigator may be terminated from the study. 
16.3 Institutional Review Board/Institutional Ethics Committee (IRB/IEC)  
Documented approval from the appropriate Institutional Review Board /Ethics Committee (IRB/IEC) will 
be obtained for all participating centers prior to study start, according to ICH GCP, local laws, 
regulations, and organization. When necessary, an extension, amendment, or renewal of the IEC 
approval must be obtained. The IEC must supply to the sponsor a list of the IRB/IEC membership and a 
statement to confirm that the IEC is organized and operates according to GCP and applicable laws and 
regulations. 
16.4 Patient Informed Consent 
A core information and consent form will be provided. Prior to the beginning of the trial, the investigator 
must have the IEC written approval/favorable opinion of the written ICF and any other written 
information to be provided to patients. The written approval of the IEC together with the approved 
patient information/ICFs must be filed in the study files. 
The process of obtaining informed consent must be in accordance with applicable regulatory 
requirement(s), and must adhere to GCP and to the ethical principles originating in the Declaration of 
Helsinki. Written informed consent must be obtained before any study specific procedure takes place. 
Participation in the trial and date of informed consent given by the patient should be documented 
appropriately in the patient files. 
16.5 Insurance 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 63 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
63 of 83 
All patients participating in the trial will have insurance coverage by the Sponsor, which is in line with 
applicable local laws. 
16.6 Confidentiality 
All records identifying the patient will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available.  
Patient names will be kept confidential. Only the patient number and initials will be recorded in the 
eCRF, and if the patient name appears on any other document, it must be obliterated. In cases were the 
local low does not allow using the patient initials serial number will be appointed (e.g. AAA, BBB). Study 
findings stored on a computer will be stored in accordance with local data protection laws. The patients 
will be informed in writing that representatives of the sponsor, IEC or Regulatory Authorities may 
inspect their medical records to verify the information collected, and that all personal information made 
available for inspection will be handled in strictest confidence and in accordance with local data 
protection laws. Patients will also be informed that information regarding the study that does not 
include patient identifiers will be posted on clinicaltrials.gov. 
If the results of the trial are published, the patient’s identity will remain confidential.  
The investigator will maintain a list to enable patients’ records to be identified. 
16.7 Use of Data and Publications 
Information regarding the study and study data will be made available via publication on clintrials.gov.  
All data and results and all intellectual property rights in the data and results derived from the study will 
be the property of NiTiNotes, who may utilize the data in various ways, such as for submission to 
government regulatory authorities or disclosure to other investigators, educational, further product 
development and marketing uses.  
The investigator, while free to utilize data derived from the study for scientific purposes, must discuss 
any publication with the sponsor prior to release and obtain written consent of the sponsor on the 
intended publication. The sponsor recognizes the right of the investigator to publish the results upon 
completion of the study. However, the investigator must send a draft manuscript of the publication or 
abstract to the sponsor 45 days in advance of submission in order to obtain approval prior to submission 
of the final version for publication. This will be reviewed promptly and approval will not be withheld 
unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the 
contents of the publication will be discussed in order to find a solution which satisfies both parties. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 64 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
64 of 83 
Disclosure of involvement in a publication (e.g., sponsor of the study; collection, analysis, and 
interpretation of data; professional writing assistance) must be as specified by journal-specific policies, 
submission requirements, and prevailing editorial standards, in addition to those specified by 
International Committee of Medical Journal Editors. Authors must ensure that an 
acknowledgement/disclosure statement is included in the body of the manuscript for NiTiNotes to 
review for accuracy. All authors must also disclose financial or personal affiliations that could be 
considered conflicts of interest as per journal requirements.  
17.0  Monitoring Procedures 
Site visits will be conducted by an authorized NiTiNotes representative to inspect study data, patients’ 
medical records, and eCRFs in accordance with current ICH GCPs and the respective local and national 
government regulations and guidelines (if applicable).The Study Investigator and the investigating site 
will permit authorized clinical research personnel and clinical monitors from NiTiNotes and/or 
designee(s) employed by NiTiNotes to review completed eCRFs, IEC  decisions, and Investigator, clinical 
site records, and facilities relevant to this study at regular intervals throughout the study per the 
monitoring plan. Additionally, patient charts and clinical records will be requested and reviewed so that 
protocol adherence and source documentation can be verified. The accuracy and quality of the data 
obtained from the investigator and maintained by NiTiNotes will be confirmed through a structured 
program of clinical field auditing and internal review detailed in the monitoring plan. In instances where 
data protection regulations prohibit the direct examination of hospital records by the study Sponsor or 
designee(s), the Investigator will cooperate in a system of source data verification with the Sponsor. 
Monitoring may be performed with in person visits or remotely, when applicable.  
To ensure the rights, safety, and welfare of study patients are being maintained, the monitor will review 
training records to ensure all study staff are trained on the study protocol and use of the study devices. 
If the monitor discovers that an investigator is not complying with the signed Investigator Agreement, 
the investigational plan, applicable laws, or any conditions of approval imposed by the reviewing IEC, 
the monitor will report to the Sponsor and take such steps necessary to promptly secure compliance. If 
compliance cannot be secured, device shipments to the investigator may be discontinued and the 
investigator’s participation in the investigation terminated. The monitor shall also require such an 
investigator to dispose of or return the device, unless this action would jeopardize the rights, safety, or 
welfare of a patient.  
17.1 Data Collection and Processing 
This study will utilize an (electronic Case Report Form) eCRFs. All data requested on the eCRFs are 
considered required. Data points not collected and/or recorded will be considered deviations unless 
otherwise specified. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 65 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
65 of 83 
The Principal Investigator must ensure the accuracy and completeness of the recorded data and then 
provide his/her signature on the appropriate eCRFs and will be documented in compliance with local 
regulations. In accordance with current ICH GCPs and the respective local and national government 
regulations and guidelines, audit trail shall be used to capture any changes to data previously entered to 
the eCRF, including when changes where made, by whom and the reason for the changes. 
Visual and/or computer data review will be performed to identify possible data discrepancies. Manual 
and/or automatic queries will be created and will be issued to the site for appropriate response. The site 
staff will be responsible for resolving all queries in the database. 
18.0  Study Supplies and Device Accountability 
18.1 Packaging 
The EndoZip disposables are composed of biocompatible parts and are supplied sterile in a sealed 
package.  
18.2 Labeling 
All packages are labeled in conformance to NiTiNotes Packaging Best Practice. Study devices will be 
labeled as “For Investigation Use Only”. 
18.3 Inventory Control 
The sponsor will initiate shipment of the product from the sponsor to the site upon receiving all required 
documents (e.g., approval/favorable opinion from IEC). The sponsor will maintain tracking for all 
shipment documentation. Prior to any shipment, the site will be informed by the sponsor of the 
upcoming shipment, expected arrival date, and content of the shipment. The site should confirm receipt 
of the shipment.  
An Investigator’s Device Accountability form will be conducted under the Regulatory Binder at each site.  
In case of technical failure, the site will approach the NiTiNotes representative which will help solve the 
problem.  
For each dispensed EndoZip, the following information should be recorded: 
• 
The patient study number  
• 
Date dispensed  
• 
Device ID number  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 66 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
66 of 83 
At the termination of the study, all unused study material must be returned with the corresponding 
documentation as directed by NiTiNotes. 
18.4 Retention of Records 
All source documents and eCRFs will be kept for a period of no less than five years after the later of the 
following dates: the date of which the study is terminated or completed or; the date that the records are 
no longer required supporting marketing applications. 
18.5 Study Completion/Termination of Study 
NiTiNotes reserves the right to discontinue the study at any stage, with suitable written notice to all 
investigators and reviewing IECs, following unforeseen events or other factors that do not permit 
continuation of the study. Similarly, investigators may withdraw from the study at any time, patient to 
providing written notification to NiTiNotes 30 days prior to the date they intend to withdraw. However, 
NiTiNotes and investigators will be bound by their obligation to complete the follow-up of patients 
already participating in the study. The patients must be followed according to the clinical protocol, and 
information obtained during patient follow-up shall be reported to NiTiNotes on the appropriate eCRF. 
The appropriate ethics committees will be notified of discontinuation of the trial for any reason not later 
than 15 working days after the sponsor makes this determination and not later than 30 days after the 
sponsor receives a notice from the ethics committee and/or regulatory authority. 
19.0  General Information 
19.1 Study Contact Information 
Questions should be directed to Clinical Affairs. 
Clinical Affairs 
Hagit Ephrath 
VP of QA, Regulatory and Clinical Affairs 
NiTiNotes Ltd. 
Address: 5 Haeshel st, PO box 3158, Caesarea, Israel 
Tel: +972-4-
 
8876698  
Fax: +972-4- 8864358 
Mobile: +972 (52) 314-2045 
Email: hagit@nitinotesurgical.com  
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 67 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
67 of 83 
19.2 Use of Data and Publications 
Information regarding the study and study data will be made available via publication on clintrials.gov.  
All data and results and all intellectual property rights in the data and results derived from the study will 
be the property of NiTiNotes, who may utilize the data in various ways, such as for submission to 
government regulatory authorities or disclosure to other investigators, educational, further product 
development and marketing uses.  
The investigator, while free to utilize data derived from the study for scientific purposes, must discuss 
any publication with the sponsor prior to release and obtain written consent of the sponsor on the 
intended publication. The sponsor recognizes the right of the investigator to publish the results upon 
completion of the study. However, the investigator must send a draft manuscript of the publication or 
abstract to the sponsor 45 days in advance of submission in order to obtain approval prior to submission 
of the final version for publication. This will be reviewed promptly and approval will not be withheld 
unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the 
contents of the publication will be discussed in order to find a solution which satisfies both parties. 
Disclosure of involvement in a publication (e.g., sponsor of the study; collection, analysis, and 
interpretation of data; professional writing assistance) must be as specified by journal-specific policies, 
submission requirements, and prevailing editorial standards, in addition to those specified by 
International Committee of Medical Journal Editors. Authors must ensure that an 
acknowledgement/disclosure statement is included in the body of the manuscript for NiTiNotes to 
review for accuracy. All authors must also disclose financial or personal affiliations that could be 
considered conflicts of interest as per journal requirements.  
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 68 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
68 of 83 
20.0 
REFERENCES 
1. World Health Organization (WHO) Obesity and overweight Fact sheet Updated June 2016 
2. Legal KM, Carroll MD, Ogdan CL, Curtin LR, Prevalence and trends in obesity among US adults 
1999-2008 JAMA, 2010 Jan 20 303 (3) 235-41. 
3. Centres for Disease Control (CDC)  
4. Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative 
nutritional, metabolic, and nonsurgical support of the bariatric surgery patient: 2013 
update—cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, 
and American Society for Metabolic & Bariatric Surgery. Surg Obes Relat Dis 2013; 9:159–191. 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 69 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
69 of 83 
21.0 
Appendix A: Post Procedure Regime 
21.1 Pre-Procedure diet 
• 
Patients will follow a clear liquid diet starting 24 hours prior to scheduled arrival time for the procedure 
• 
Patients will be NPO after midnight the night before the procedure. (exception - small sips of water for 
medication) 
21.2 Post Procedure Diet 
At each individual session, dietitians will perform a diet recall and exercise recall to determine 
compliance with the diet recommendations and the exercise goals.  The dietitian will discuss the 
barriers patients have that may be preventing them from achieving their diet recommendations and 
their exercise goals.  In conjunction with the patient, the dietitian will set 1-3 goals for the patients to 
work on before the next session. 
The patient will be under the following diet regime from Day 0 to Week 8 Post Procedure (PP, Table 1) 
 
Table 1. Diet Progression 
Phase 
Duration 
Types of Liquids 
or Foods 
Protein Goal 
Notes 
Phase 1: Clear 
liquid diet 
PP Day 1 to 
PP Day 3 
Clear Liquids 
only 
60-80 gm 
• 
Will need protein 
supplement to maintain 
protein goals 
• 
Focus on protein intake, 
adherence to clears, and 
sufficient liquids to avoid 
dehydration 
total calories may be low 
Phase 2: Full 
liquid diet 
PP Day 4-PP 
Day 14 
Full Liquids and 
Clear Liquid 
60-80 gm 
• 
Will need protein 
supplements to maintain 
protein goals 
• 
Still need to focus more on 
protein intake and 
sufficient liquids to avoid 
dehydration 
• 
Total calories may be low, 
but if patient can maintain 
activities, hydration, and 
energy level do not force 
additional intake 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 70 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
70 of 83 
Phase 
Duration 
Types of Liquids 
or Foods 
Protein Goal 
Notes 
Phase 3: 
Semi-Liquid 
(Pureed) Diet 
PP Day 15 to 
PP Day 42 
Pureed Food, 
Full Liquids, and 
Clear Liquids 
60-100gm  
(higher protein 
range for tall 
patients and 
men) 
• 
May still need protein 
supplements 
• 
Eat pureed meals slowly – 
discomfort can occur 
quickly  
Avoid fluid intake within 30 
min of a meal 
Phase 4: 
Semi-Solid 
Diet  
PP Week 6-
PP Week 8 
Add soft foods 
that can be 
easily chewed 
60-100 gm 
(higher protein 
range for taller 
patients and 
men) 
• 
Still continue to eat slowly 
and chew food well 
• 
Continue to drink between 
meals and stop 30 min 
before a meal 
Phase 5: 1200 
– 1500 
Calories Diet 
 
 
 
 
21.3 Phase 1: Clear Liquids Only 
Water-based diet for 2-3 days after the procedure. 
Recommendation for Patients: 
• 
You can start Clear Liquids when awake after the procedure. 
• 
Clear liquids are liquids that you are able to see through when you hold up a glass of the liquid to light. 
Examples include sugar-free and room temperature water, light tea, chamomile, herbal teas, and 
Jelly.   
• 
They are easily digested and leave no undigested residue in your intestinal tract.  
• 
Medium temperature or room temperature liquids may be better tolerated than extremely cold and 
extremely hot liquids after the procedure. 
• 
For adequate protein on a clear liquid diet, you NEED to supplement. 
• 
Aim for 60g of protein per day and 48 fluid ounces per day. You can purchase protein powder online 
• 
Consume 2 tablespoons/30 cc of clear liquids every 15 minutes in order to maintain hydration. 
• 
Use a timer to accurately track 15 minutes and avoid dehydration. 
• 
Avoid caffeine and alcohol for 1 month, as these can cause stomach irritation and dehydration as you 
heal. 
• 
Avoid sugary drinks, which can lead to diarrhea. 
• 
Avoid carbonated beverages for 1 month, along with using straws, as this can lead to the swallowing of 
more air. 
• 
Do not gulp liquids – be sure to sip. 
• 
Avoid chewing gum to prevent taking in more air as well. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 71 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
71 of 83 
21.4 Phase 2: Full Liquid Diet 
Recommendation for Patients: 
• 
All liquids should pour off a spoon.   
• 
Consume foods that are liquid or semi-liquid at room temperature. 
• 
You may not feel hungry most of the time and find it difficult to eat even three times a day.  
• 
Small portions sizes are essential! 
• 
Eat your meals slowly. Allow for 20-30 minutes per meal.  
• 
Drink water or zero-calorie fluids throughout the day.  
o 
Your goal is 1.5 liters of fluids a day, working up to 2 liters of fluids a day.  
o 
Drink between meals but not right before or during. 
o 
NO straws. You can suck up too much air and cause discomfort.  
o 
Sip, sip, sip. 
Recommended Foods: 
• 
Any of the food from Stage 1-Clear Liquids 
• 
Milk or milk alternatives (low-fat or non-fat is preferred). 
• 
Creamed soups  
• 
Broth based soups run through the blender, no lumps or bumps 
• 
Protein supplement drinks 
o 
With at least 15g protein and less than 3g of sugar. 
o 
Popular brand: Unjury Protein or Premier Protein  
• 
Thinned hot cereal: 
o 
Cream of wheat 
o 
Instant oatmeal 
• 
Thinned mashed potatoes (thinned with chicken, vegetable, or beef broth) 
o 
Flavoring ideas: 
▪ 
Thyme, oregano, basil, garlic, onion powder 
▪ 
Packaged gravy mix 
• 
Low-sugar yogurt or sugar-free pudding 
• 
Low-sugar light, drinkable yogurt 
 
Between Meal Liquids: (low calorie, less than 10 Calories per 8 fluid ounces) 
• 
Water 
• 
Sugar-free flavored drink packets 
• 
Broth 
• 
Decaffeinated coffee or tea – fat free creamer and sugar substitute are OK 
• 
Tomato or vegetable juice (limit to 6 fluid ounces per day) 
 
Sample Meal Plan: 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 72 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
72 of 83 
Between meals liquids (low calories, less than 10 calories per 220 cc liquids – 1 cup) 
• 
Water 
• 
Sugar-free flavored drink packets 
• 
Decaffeinated coffee or tea – fat free creamer and sugar substitute are OK  
• 
Tomato or vegetable juice (limit to 175 cc fluids per day) 
 
Breakfast – 120ml of Semolina / rice cream 
Snack – 120ml of 1% milk with a spoon of protein powder / other protein drink 
 
Lunch – 120ml creamed soup 
Snack – 120ml of 1% milk with a spoon of protein powder / other protein drink 
 
Dinner – 120ml filtered chicken soup 
Snack – 120ml of 1% milk with a spoon of protein powder / other protein drink 
 
21.5 Phase 3: Semi-Liquid (Pureed) Diet 
Recommendation for Patients: 
This diet includes: 
• 
Foods that do not need much chewing.   
• 
Typically, ground, pressed, blended, or sieved to the consistency of a soft creamy paste or thick 
liquid.  
• 
Continue drinking fluid between your meals, but stop 30 minutes before your meal and start again 
60 minutes after your meal. 
 
Recommended Foods: 
• 
All foods from the clear liquid and full liquid diets 
• 
Low-sugar yogurt  
• 
Low-fat white cheese 
• 
Scrambled eggs 
• 
Pureed beef, chicken, or turkey 
• 
White fish mashed finely with a fork 
• 
Tuna mashed finely with a fork 
• 
Mashed or pureed potatoes/sweet potatoes 
• 
Pureed cooked butternut squash 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 73 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
73 of 83 
• 
Pureed cooked spinach, carrots, green beans 
• 
Tahani 
• 
Avocado 
• 
Banana 
Sample Meal Plan: 
Snacks (mid morning and mid afternoon) 
• 
120 ml skimmed milk  
• 
125 g low fat white yogurt / cheese  
• 
1 teaspoon almond butter  
• 
I teaspoon of natural peanut butter  
• 
1 spoon of tahini   
Breakfast – 1 scrambled egg + 0.5 cup of low fat white cheese + decaffeinated coffee/tea 
Snack – 130g Fruit puree  
Lunch – 100-150 g Pureed beef, chicken, or turkey + 100 ml vegetable puree (chard, spinach, 
lettuce, zucchini, broccoli)  
Snack – 125 g low fat white yogurt 
 
Dinner – 120ml filtered chicken soup 
Snack – 120ml of 1% milk with a spoon of protein powder / other protein drink 
 
21.6 Phase 4: Semi-Solid Diet 
 
Table 2. Phase 4 and 5: Protein goals and Maximum calorie amounts 
Start Weight 
68-89 
90-112 
113 and above 
Calories or 
Protein 
kcal 
protein 
kcal 
protein 
kcal 
protein 
Amount 
1200 
60-80 
1300 
70-90 
1500 
80-100 
Both calories and protein need to be tailored to the patient.   The calories listed are the 
maximum goals – patients should not eat over this amount, but can eat less.  Many patients will 
eat less than these calorie levels in the first few months after the procedure.  
If patients are eating less than the amounts listed below, have no evidence of dehydration and 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 74 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
74 of 83 
have good energy levels they do not need to force additional calorie intake.  Forcing 
food/volume can lead to patient discomfort / adverse events and should be avoided. 
Recommendation for Patients: 
This diet includes: 
• 
Foods that are easily chewed and swallowed.   
• 
Avoid foods that are hard like nuts, popcorn, or seeds, stringy like cooked onions and cooked bell 
peppers, or tough like dried fruit or smoked meats.  
• 
Avoid foods that can cause gas like broccoli, Brussel sprouts, cabbage, cauliflower, bell peppers and 
onions.   
• 
Vegetables should still be cooked in this phase and all food should be chewed thoroughly. 
Recommended Foods: 
• 
Anything in the prior diet phases 
• 
Moist and tender meats 
• 
Cooked or canned fruits 
• 
Banana 
• 
Avocado 
• 
Tahini 
• 
Cooked vegetables 
• 
Plain, white rice, pasta-no more than 1/3 of a cup 
• 
Refined wheat bread 
• 
Homemade hummus 
Snacks (mid morning and mid afternoon) 
• 
120 ml skimmed milk  
• 
125 g low fat white yogurt / cheese  
• 
25g light Emmental cheese 
• 
1 teaspoon almond butter  
• 
I teaspoon of natural peanut butter  
• 
1 spoon of tahini / avocado spread 
• 
3 spoons smooth homemade hummus 
• 
130g Fruit puree 
Sample Meal Plan: 
 
Breakfast – 1 scrambled egg + 25g light Emmental cheese + decaffeinated coffee/tea 
Snack – 130g Fruit puree  

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 75 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
75 of 83 
Lunch – 160 g fish pureed or well chopped + Ricotta 70 g / Philadelphia light 60g + 110 g mashed 
or pureed potatoes/sweet potatoes 
Snack – 120ml of 1% milk with a spoon of protein powder / other protein drink 
 
Dinner –20 g Semolina / rice cream / small pasta in 100ml vegetable broth + 5 g parmesan 
cheese  
 
21.7 Phase 5: 1200 – 1500 Calories Diet 
Recommendation for Patients: 
This diet includes: 
• 
1,200-1,500 kcal/day diet 
• 
60-80g of protein/day (20g of protein at breakfast) 
• 
Eat small amounts, several times a day. 
• 
Set utensils down in-between bites. 
• 
Eat slowly, and stop at first sign of fullness. 
• 
Chew foods thoroughly. 
• 
Drink non-caloric beverages, avoid drinking gassy beverages, and drink in-between meals. 
 
The following menu is designed according to the following calorie distribution: 
• 
Breakfast – 200 -300 calories 
• 
Snacks - 100 calories 
• 
Lunch – 500 - 600 calories 
• 
Snacks - 100 calories 
• 
Evening – 300 - 400 calories 
 
Sample Meal Plan: 
 
Breakfast: 
1 cup of low fat white yogurt (you can use yogurt enriched with protein 20 grams of natural 
protein) + half a cup of freshly cut fruit, 5 almonds / nuts 
OR 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 76 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
76 of 83 
2 slices of light bread made from rye / spelled / 3 slices of cracker made from rice / buckwheat / 
corn (each up to 30 calories) / a half pita beard made from whole wheat / spelled + 1 spoon of 
white cheese 5% + hard-boiled egg + slices of vegetable (tomato / cucumber / red pepper) and 
leaf . lettuce 
OR 
3 spoons oatmeal + 0.5 cup of skimmed milk / herbal drink + 0.5 cup of water + chopped fresh 
banana and a little cinnamon 
 
 
Snacks: 
1.5 cup melon / watermelon cubes or other fresh fruit (1 medium unit) 
OR 
2 spoons white cheese 5% with fresh vegetables (5 cherry tomatoes, cucumber + 0.5 carrot) 
 
Noon: 
150 g baked salmon (can be used with herbs and lemon) / chicken breast + 3 spoons whole rice / 
quinoa / medium sweet potato + a cup of green beans in tomato sauce / a small bowl of 
(volume of a cup) vegetable salad with 1 teaspoon of olive oil / 1 spoon avocado 
OR 
120 grams of tofu cubes + 0.5 cup of cooked rice noodles or quinoa noodles + 2 cups of stir-fried 
vegetables (such as carrots, celery, mushrooms, onions, cabbage, cauliflower, broccoli ...) - for 
the sauce - 2 spoons soy sauce and 1 spoon of olive oil 
Snacks: 
Energy snack up to 100 calories / 1 date palms or 1 fresh fruit + 4 walnut or almond halves /  
Ice cream up to 100 calories / 2 crackers (up to 30 calories per unit) + a teaspoon of jam / honey 
on each cracker  
 
Evening: 
Omelet (1 egg) with herbs (onion, parsley, rocket, spinach) + 2 spoons cheese / white cheese 5% 
with vegetable salad + quarter avocado + 2 slices light bread / 1 slice of bread   made from 
whole wheat  / spelled / rye  
OR 
Tuna salad: 50 grams (one third of a box) tuna in water + hard-boiled egg + vegetable salad with 
a seasoning of 1 teaspoon of olive oil, half pita bread from spelled / whole wheat (up to 100 
calories per pita) 
OR 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 77 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
77 of 83 
1 cup of low fat white yogurt (you can enriched with natural-flavored protein) + whole apple + 
half pear + half nectarine + 2 flat spoons of granola without added sugar + 1 teaspoon of chia 
seeds 
21.8 General Instructions 
The information supplements the diet plan (divided into progressive phases) described above.   
They have been inserted to help operated patients to change their eating habits in order to reduce 
complications and side effects after the EndoZip procedure. 
 
• 
The re-feeding phase duration (respecting the indicated times) will be strictly related to 
individual tolerance. If the introduction of new foods or foods with a different consistency 
might determine excessive gastric filling or vomiting, please return to previous PHASE diet for 
2-3 days.  
• 
Eat slowly, chewing your food well and stopping between one bite and the next. The meal 
must last at least 30-40 minutes. 
• 
Stop eating as soon as you feel full (regardless of the amount of food ingested). Insisting 
would cause vomiting. 
• 
Start lunch and dinner with the protein dish to ensure adequate protein intake during weight 
loss; then continue the meal with vegetables, fruit and finally the first course. 
• 
Avoid eating and drinking at the same time. 
• 
Do not induce vomiting. 
• 
Eat the evening meal at least 2 hours before bedtime, to avoid the onset of gastroesophageal 
reflux. 
• 
Drinks should be taken at least half an hour after the meal (before or after). 
• 
Drink, initially, at least 1 liter of water during the day, only natural, in small sips. Tea, 
chamomile, barley, preferably decaffeinated coffee, herbal teas as long as they are sugar-free 
or using natural sweeteners based on Stevia are also allowed. 
• 
Avoid the consumption of carbonated, sugary, alcoholic and spirits drinks. 
• 
Vegetables should not be eaten in the first few weeks; they will then be reinserted gradually 
and in small quantities in the form of pureed vegetables or finely chopped. 
• 
Avoid the consumption of foods containing simple sugars and fats (sweets, jams, honey, 
croissant, chocolate, ice cream, dried and canned fruit, fruit juices, spicy cheeses, sausages, 
sauces and various condiments). 
• 
Avoid foods that are too spicy, too hot or too cold. 
• 
In the final phase, divide up the meals of the day respecting the times (3 main meals + 1 mid-
morning and mid-afternoon snack). Any changes must be agreed with the doctor. 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 78 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
78 of 83 
• 
In case of constipation make sure to introduce an adequate supply of water. However, it is 
possible that the doctor will recommend taking laxatives. 
• 
Gradually increase physical activity (after consulting your doctor and based on your physical 
condition), so as to preserve muscle mass in conjunction with weight loss.  
 
21.9 Physical Activity 
For patients who exercised regularly (defined as at least 3 days per week for at least 30 minutes per 
session) before the procedure can return to exercise as tolerated once they are at least on a full liquid 
diet and have no post-procedure symptoms.  For patients who have never exercised before, consider 
the following exercise titration in Table 2 after the patient has advanced to a pureed diet and their post-
procedure symptoms have resolved.   
1. The recommended exercise is at least moderate intensity exercise (brisk walk). High intensity 
training and high intensity interval training are also acceptable. Strength training is also 
encouraged 
2. Goals: after return to exercise or titration of exercise 150 minutes of at least moderate intensity 
exercise (e.g. brisk walk with moderate breathing) per week 
 
Table 2. Exercise progression 
Week Post procedure 
Moderate Intensity 
Exercise Duration 
Sessions Per Week 
2 Weeks PP 
15 minutes 
3 
3 Weeks PP 
15 min 
4 
4 Weeks PP 
20 min 
4 
5 Weeks PP 
20 min 
5 
6 weeks PP 
30 min 
5 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 79 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
79 of 83 
22.0 Appendix B – Usability Questionnaire (filled-in by the physician) 
 
1. How was it to remove the system from the pack maintaining its sterility? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
2. How was the system setting up with respect to the followings? 
a. Connect to the electricity 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
b. Connect to the vacuum pump system 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
c. Connect to the Endoscope system 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
d. Connect to the CO2 system (if used) 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
 
     N/A (if CO2 not been used during the procedure) 
3. How was the insertion of the scope into the EndoZip device? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 80 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
80 of 83 
4. How was the system advancement to the stomach through the Overtube? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
5. How was the maneuvering process within the stomach to the desired suturing location? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
6. For insufflation, did you use the EndoZip CO2 channel?       Yes       No 
a. If No, how was the insufflation process using the endoscope insufflation channel? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
b. If Yes, how was the insufflation process using the endoscope and the EndoZip CO2 extra 
channel? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
7. How was the overall management of the system’s stopcocks, clamps and valves (vacuum and CO2 
insufflation)? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
8. How was the overall management of the system’s knobs (for proximal and distal articulation)? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 81 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
81 of 83 
9. How easy was the activation of operation button? (suturing, tightening, clipping and cutting 
process) 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
10. How easy was the identification of suturing stage through the system user panel (LEDs)? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
11. How was the Corset wire release process (before system retrieval)? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
12. How was the system retrieval process? 
Very Easy 
Easy 
Acceptable 
Difficult 
Very Difficult 
5 
4 
3 
2 
1 
 
 
General impression: 
1. How was the general touch and feel working with the EndoZip system? 
Excellent 
Good 
Acceptable 
Difficult 
Unacceptable 
5 
4 
3 
2 
1 
 
2. How was the use of Endozip system, comparing to ESG alternatives? 
Significantly Easier 
Easier 
Same 
Inferior 
Significantly Inferior 
5 
4 
3 
2 
1 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 82 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
82 of 83 
Please grade your agreement with the following statements: 
3. I think that I would like to use this system frequently 
Strongly Agree 
 
 
 
Strongly Disagree 
5 
4 
3 
2 
1 
4. I thought the system was easy to use 
Strongly Agree 
 
 
 
Strongly Disagree 
5 
4 
3 
2 
1 
5. I think that I would need the support of a technical person to be able to use this system 
Strongly Agree 
 
 
 
Strongly Disagree 
5 
4 
3 
2 
1 
6. I found the various functions in this system were well integrated 
Strongly Agree 
 
 
 
Strongly Disagree 
5 
4 
3 
2 
1 
7. I found the IFU (Instruction For Use) very informative and provides sufficiently the information 
needed to perform the procedure 
Strongly Agree 
 
 
 
Strongly Disagree 
5 
4 
3 
2 
1 
 
 
Comments____________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________
_____________________________________________________________________________________ 
 
 
 

 
 
 
  
CL00003/ Protocol, Version 1.0; January13, 2021 
 
Page 83 of 83 
 
 
Title: 
Evaluation of EndoZipTM System (AS) in Obese Patients who failed to 
reduce weight with non-surgical weight-loss methods 
Document No: 
CL00003 
Rev: 
1.0 
Page: 
83 of 83 
23.0 
Appendix C – Patients Diary (filled-in by the patients)  
 
Date: ___ / ___ / 2021 
           dd     mm 
 
Breakfast 
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________ 
Snack 
_________________________________________________________________
_________________________________________________________________ 
Lunch 
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________ 
Snack 
_________________________________________________________________
_________________________________________________________________ 
Dinner 
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________