A Randomized, Open-label, Multi-center, Controlled Clinical Study to Compare MAR-CUTIS With Dermabond Advanced in Closure of Surgical Incisions and Lacerations up to 15 Centimeters
Phase: NA
Conditions: Wounds and Injuries, Lacerations, Surgical Incision
Sponsor: Grünenthal GmbH

CLINICAL STUDY PROTOCOL 
A Randomized, Open-label, Multi-center, Controlled Clinical Study to 
Compare MAR-CUTIS with Dermabond Advanced in Closure of Surgical 
Incisions and Lacerations ≤15cm 
Protocol Number: 
KF7021-04 
ClinicalTrials.gov Identifier: 
NCT03688880 
EudraCT Number: 
Not applicable 
Syneos Health Study Number: 
1012937 
Investigational Product: 
MAR-CUTIS topical tissue adhesive 
Phase: 
Pivotal 
Investigational Device 
Management Category: 
European Union: IIb; United States: II 
Sponsor: 
Grünenthal GmbH 
Zieglerstraße 6 
52078 Aachen 
Germany 
Contract Research Organization: Syneos Health 
3201 Beechleaf Court 
Suite 600 
Raleigh, NC 27604-1547 
United States 
Protocol Date: 
25 Feb 2019 
Protocol Version: 
Version 4.0 
CONFIDENTIAL 
This protocol may not be reproduced or communicated to a third party without the 
written permission of Grünenthal GmbH. 

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SUMMARY OF CHANGES 
Amendment Type: 
Substantial 
Rationale for Amendment: 
 The protocol tries to avoid the inclusion of patients 
who are on chronic treatment with drugs known to 
interfere with wound healing and/or are known to 
trigger wound healing complications like haematoma. 
Unfortunately, the chosen phrase in Version 3.0 of the 
protocol prohibits the application of steroids, 
immunosuppressants, chemotherapy, or anticoagulants 
with the exception of anti-platelet therapies 
pre-operation and also post-operatively. This was 
never intended and indeed would be against 
established deep vein thrombosis prophylaxis 
regimens, neo-adjuvant chemotherapies etc. 
The proposed amendment of the protocol corrects this 
aspect. 
Summary of Amendment: 
See below. 
Section 
Change Made 
Rationale for Change 
Cover page and 
header 
Protocol version and date changed to 
v4.0, 25 Feb 2019. 
Protocol Approval 
Signature page 
Change of one of the CRO signatories 
from 
 to 
 
Synopsis and 
Section 7.3.3 
Exclusion Criterion #8 
Subjects requiring suturing with sutures 
>5-0 0.5 mm thickness 
Exclusion Criterion #12  
Subjects receiving chronic, pre-
operative steroids, 
immunosuppressants, chemotherapy, or 
anticoagulants; only chronic 
anti-platelet therapies like ASA and 
clopidogrel are accepted. Chronic is to 
be interpreted as long term or “for 
more than acute treatment”. 
Pre-operative standard of care, like a 
single dose of an anticoagulant, for 
the aforementioned treatments is 
allowed along with standard of care 
post-operative anticoagulant and 
chemotherapy regimen including 
application of steroids and 
immunosuppressants. 
Clarification to avoid 
confusion which arose from 
the use of a USP and metric 
combination to describe the 
suture thickness. 
To allow application of 
steroids, 
immunosuppressants, 
chemotherapy, or 
anticoagulants with the 
exception of anti-platelet 
therapies pre-operatively 
and post-operatively, to be 
in line with established 
deep vein thrombosis 
prophylaxis regimens, 
neo-adjuvant 
chemotherapies, etc. 
Section 7.4.8.1 
Prohibited medications are chronic, 
To allow application of 

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Section 
Change Made 
Rationale for Change 
Prohibited 
Medication/Therapy 
pre-operative steroids, 
immunosuppressants, chemotherapy, 
and anticoagulants; only chronic anti-
platelet therapies like acetylsalicylic 
acid (ASA) and clopidogrel are 
accepted. Chronic is to be interpreted 
as long term or “for more than acute 
treatment”. Pre-operative standard of 
care, like a single dose of an 
anticoagulant, for the aforementioned 
treatments is allowed along with 
standard of care post-operative 
anticoagulant and chemotherapy 
regimen including application of 
steroids and immunosuppressants. 
steroids, 
immunosuppressants, 
chemotherapy, or 
anticoagulants with the 
exception of anti-platelet 
therapies pre-operatively 
and post-operatively, to be 
in line with established 
deep vein thrombosis 
prophylaxis regimens, neo-
adjuvant chemotherapies 
etc. 
Throughout 
protocol 
Corrections to typographical and 
grammatical errors. 
To improve readability. 

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CONFIDENTIAL 
2 
SYNOPSIS 
Protocol Number: 
KF7021-04 
Title: 
A randomized, open-label, multi-center, controlled clinical study to compare MAR-CUTIS with Dermabond 
Advanced in closure of surgical incisions and lacerations ≤15 cm. 
Investigational Device: 
MAR-CUTIS topical tissue adhesive 
Study Centers: 
Up to 22 study centers located in the European Union 
Phase: 
Pivotal 
Investigational Device Management Category: 
European Union: IIb; United States: II 
Study Design: 
This is a randomized, open-label, multi-center, comparator-controlled clinical study to compare MAR-CUTIS 
with Dermabond Advanced in closure of surgical incisions ≥6 to ≤15 cm and lacerations ≤15 cm. Eligible 
subjects will be randomized 2:1 to MAR-CUTIS or Dermabond Advanced. 
Number of Subjects: 
A total of 189 subjects will be treated (defined as study product applied to the wound). Only subjects that are 
withdrawn from the study due to product failure at the time of application will be replaced. Re-screening is not 
allowed in the study. 
Treatment: 
MAR-CUTIS or Dermabond Advanced topical tissue adhesive will be applied to surgical incisions ≥6 to 
≤15 cm and lacerations ≤15 cm as a last dermal closing layer on Day 0 once wounds have been prepared in a 
standard manner. 
Study Duration: 
The overall study duration for each subject is up to 4 months: 

Day -21 to Day 0: screening, presurgical examination.

Day 0: presurgical examination, surgery, final eligibility, allocation to treatment group, treatment.

Follow-up visits: Day 1, Day 10, Month 1, and Month 3 or Early Discontinuation.
Study Population: 
Inclusion Criteria 
For subjects with surgical incisions: 
1.
Subject undergoing closure of surgical incision ≥6 to ≤15 cm following a laparotomy, abdominal
hysterectomy, inguinal hernia repair, or laparoscopic intervention.
For subjects with lacerations: 
2.
Subject requiring closure of a laceration on face (avoiding the immediate area around the eye or
lips/mouth) or extremities, ≤15 cm. In subjects with multiple lacerations, one will be selected as the
target wound (ie, greatest length and meets the study entry criteria).
For all subjects: 

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3.
Subject has the ability to consent and has given written informed consent/assent to participate.
4.
Male and female subjects ≥2 years of age and body weight ≥10 kg.
5.
Subject willing and capable of following instructions for wound care provided by the investigator and
agreeing to return for all treatment control visits specified in this clinical study.
Exclusion Criteria 
For subjects with lacerations: 
1.
Wounds on mucosal surfaces or across mucocutaneous junctions (eg, oral cavity, lips, eyes).
2.
Wounds which may be regularly exposed to body fluids or with dense natural hair (eg, scalp); wounds
on ears.
3.
Wounds on palms and feet.
4.
Animal or human bites.
5.
Lacerations that are heavily contaminated.
6.
Punctured or crushed wounds.
7.
Subjects with lacerations having wound treatment >6 hours after the trauma.
For all subjects: 
8.
Subjects requiring suturing with sutures >0.5 mm thickness.
9.
Subject with documented skin disease or skin conditions (eg, excessive hair at the site of surgery, scar
tissue, wound, tattoo, coloration, or pre-existing open sores at the site of surgery that would interfere
with the application of investigational medical device [IMD] or the skin assessment, as judged by the
investigator).
10. Subject with any factors that may have an adverse effect on wound healing (eg, previous history of
keloid formation or hypertrophy [including family history]), other general risk factors for dehiscence
(need of premature post-surgery exercise/heavy lifting, expected conditions leading to recurrent
vomiting, coughing, or constipation), history of immunosuppression, chronic systemic infection, or
poor general health.
11. Subjects with known blood clotting disorders.
12. Subjects receiving chronic, pre-operative steroids, immunosuppressants, chemotherapy, or
anticoagulants; only chronic anti-platelet therapies like acetylsalicylic acid (ASA) and clopidogrel are
accepted. Chronic is to be interpreted as long term or “for more than acute treatment”. Pre-operative
standard of care, like a single dose of an anticoagulant, for the aforementioned treatments is allowed
along with standard of care post-operative anticoagulant and chemotherapy regimen including
application of steroids and immunosuppressants.
13. Subject having known or suspected allergy or sensitivity to polyurethane, cyanoacrylates,
formaldehyde, tapes or adhesives, or benzalkonium chloride.
14. Subject participating in any current clinical study with a non-Conformité Européenne–marked device
or investigational product.
15. Subject who is pregnant or breastfeeding.
16. Subject with history of a significant dermatologic disease or condition, such as atopic dermatitis,
psoriasis, lichen ruber planus, vitiligo or conditions known to alter the skin appearance or physiologic
response (eg, decompensated diabetes mellitus, porphyria) that involves the investigative site.

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Withdrawal Criteria: 
Subjects will be withdrawn from the study if the adhesive does not adhere appropriately at the time of 
application as assessed by the investigator and the event will be reported as device deficiency. 

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Objectives and Endpoints: 
Objectives 
Endpoints 
Primary Efficacy Objective: 
 
To compare the dehiscence rate between 
MAR-CUTIS and Dermabond Advanced 
between Day 1 and Day 10.  
Primary Efficacy Endpoint: 
 
Total dehiscence rate of target 
incision/laceration assessed at the Day 10 visit. 
Main safety objective: 
 
To compare the incidence of adverse events 
between MAR-CUTIS and Dermabond 
Advanced.  
Main safety endpoint: 
 
Adverse events within 1 month after treatment 
classified by severity and relatedness to the 
treatment.  
Secondary 
 
To compare the dehiscence rate between 
MAR-CUTIS and Dermabond Advanced at the 
Month 1 visit.  
 
Total dehiscence rate of target 
incision/laceration assessed at the Month 1 or 
Early Discontinuation visit (if Early 
Discontinuation occurs before Month 1).  
 
 
To compare the incidence of adverse events 
between MAR-CUTIS and Dermabond 
Advanced at additional study time points.  
 
Adverse events classified by severity and 
relatedness to the treatment.  
 
 
To evaluate the subject satisfaction with the 
cosmetic outcome after treatment of the 
surgical incision/laceration with MAR-CUTIS 
versus Dermabond Advanced 
 
Subject-completed Patient and Observer Scar 
Assessment Scale (POSAS) done at the Month 
1 and Month 3 visits or at the Early 
Discontinuation visit (if Early Discontinuation 
occurs before Month 1). 
 
To compare the wound infection incidence 
between both treatment groups. 
 
 
 
 
Wound infection incidence assessed at the 
Day 10, Month 1, and Month 3 visits or at the 
Early Discontinuation visit (diagnosed 
according to the Centers for Disease Control 
and Prevention criteria for surgical site 
infection). 
 
Wound infection assessed on a binary scale 
(“1 - yes” or “0 - no”) for the following 
criteria: 
o 
Presence of erythema 
o 
Presence of edema 
o 
Presence of pain at rest 
o 
Presence of elevated temperature 
A total score will be calculated for each subject.  
 
To evaluate the investigator satisfaction with 
the cosmetic outcome after the closure of the 
target surgical incision/laceration with MAR-
CUTIS versus Dermabond Advanced. 
 
Investigator-completed POSAS done at the 
Month 1 and Month 3 visits or at the Early 
Discontinuation visit. 
 
Investigator-completed Modified Hollander 
Cosmesis Scale (mHCS) done at the Day 10 
and Month 1 visits or at the Early 
Discontinuation visit (if Early Discontinuation 
occurs before Month 1). 
 
To evaluate the subject comfort with the device 
during and after treatment with MAR-CUTIS 
versus Dermabond Advanced. 
 
A questionnaire related to subject experience 
and satisfaction with the device completed by 
the subject at the Day 10 and Month 1 visits 
or at the Early Discontinuation visit (if Early 
Discontinuation occurs before Month 1). 
 
A subject-related questionnaire to be 
completed by investigators at the Day 0 and 
Month 1 visits or at the Early Discontinuation 
visit (if Early Discontinuation occurs before 

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Objectives 
Endpoints 
Month 1). 

To evaluate the investigator overall satisfaction
and ease of use with the device during and after
the closure of the target surgical
incision/laceration with MAR-CUTIS or
Dermabond Advanced.

A product-related questionnaire completed by
investigators at the Month 1 or Early
Discontinuation visit (if Early Discontinuation
occurs before Month 1).
Statistical Analysis: 
Assuming dehiscence rates of 3.05% for MAR-CUTIS and 0.85% for Dermabond Advanced, 189 subjects (2:1, 
126 MAR-CUTIS versus 63 Dermabond Advanced) ensure a power of 85% to show noninferiority of 
MAR-CUTIS compared with Dermabond Advanced using a one-sided significance level of α = 0.05 and a 
Farrington-Manning test given a noninferiority margin of 8%. 
The assumed dehiscence rates of 3.05% and 0.85% were derived based on the assumption to have 15% of 
subjects in the trial with lacerations that have a dehiscence rate of 0.5% for MAR-CUTIS and 0% for 
Dermabond Advanced and 85% of subjects in the trial with incisions, with dehiscence rates of 3.5% for 
MAR-CUTIS and 1% for Dermabond Advanced.  
The assumed noninferiority margin of 8% is based on an average of dehiscence rates observed in previous 
studies eg, Siddiqui et al 2013 (dehiscence between 2%-13%), Muncie et al 2018 (dehiscence rates between 0.8-
7.5%), and Eymann et al 2010 (dehiscence rates between 2%-24%). Noninferiority versus a placebo would not 
be ethical in the context of this trial, and thus has been set conservatively versus an approved IMD 
(Dermabond). 
Descriptive statistics for the efficacy parameters will be based on the Full Analysis Set and for the safety and 
tolerability parameters based on the Safety Analysis Set. Summaries will be provided by treatment and time 
point (if applicable). 
For the primary efficacy endpoint, Maximum-Likelihood estimates will be obtained fitting a logistic regression 
model to the dehiscence rates using the skin type (types I to III/types IV to VI), age group (2 to 21 years and 
≥22 years), type of wound (incision/laceration) and treatment as explanatory variables. The method of 
Farrington-Manning (FM) will be applied to determine the variance estimator. Based on the derived Maximum-
Likelihood estimates for the dehiscence rates and the FM estimate for the variance, the p-value of the FM test 
regarding noninferiority and the 90% confidence interval for the difference in dehiscence rates will be 
determined. The noninferiority of MAR-CUTIS compared with Dermabond Advanced will be established if the 
upper limit of this confidence interval is below the noninferiority margin of 8%. 
A sensitivity analysis will be performed considering the length of incision/laceration in the logistic regression 
model instead of the wound type. Other sensitivity analyses will be performed as well. 
All endpoints other than the primary efficacy endpoint will only be investigated descriptively in an exploratory 
manner. 

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3 
TABLE OF CONTENTS 
SUMMARY OF CHANGES ................................................................................................... 2 
1 
PROTOCOL APPROVAL SIGNATURES ............................................................ 4 
2 
SYNOPSIS .................................................................................................................. 6 
3 
TABLE OF CONTENTS ........................................................................................ 11 
4 
LIST OF ABBREVIATIONS ................................................................................. 14 
5 
INTRODUCTION ................................................................................................... 15 
6 
STUDY OBJECTIVES ........................................................................................... 18 
7 
INVESTIGATIONAL PLAN ................................................................................. 20 
7.1 
Overall Study Design and Plan: Description ......................................................... 20 
7.1.1 
Study Design ............................................................................................. 20 
7.1.2 
Schedule of Assessments .......................................................................... 21 
7.2 
Discussion of Study Design ..................................................................................... 23 
7.2.1 
Study Design ............................................................................................. 23 
7.3 
Selection of Study Population ................................................................................. 24 
7.3.1 
Number of Planned Subjects .................................................................... 24 
7.3.2 
Inclusion Criteria ...................................................................................... 24 
7.3.3 
Exclusion Criteria ..................................................................................... 25 
7.3.4 
Removal of Subjects From Therapy or Assessments ............................... 26 
7.4 
Investigational Medical Device ............................................................................... 27 
7.4.1 
Investigational Medical Device Applied .................................................. 27 
7.4.2 
Identity of Investigational Medical Device .............................................. 27 
7.4.3 
Manufacturing, Packaging, and Labeling ................................................. 28 
7.4.4 
Method of Assigning Subjects to Treatment Groups ............................... 28 
7.4.5 
Application in the Study ........................................................................... 28 
7.4.6 
Timing of Application for Each Subject ................................................... 29 
7.4.7 
Blinding .................................................................................................... 29 
7.4.8 
Prior and Concomitant Therapy ................................................................ 29 
7.4.9 
Treatment Compliance .............................................................................. 30 
7.4.10 
Device Deficiencies Reporting ................................................................. 30 
8 
TIMING OF STUDY PROCEDURES .................................................................. 30 
8.1 
Treatment ................................................................................................................. 30 
8.1.1 
Screening Visit (Day -21 to 0) .................................................................. 30 
8.1.2 
Baseline Visit (Day 0) .............................................................................. 30 
8.2 
Follow-up Period ...................................................................................................... 31 
8.2.1 
Day 1 ......................................................................................................... 31 
8.2.2 
Day 10 and Month 1 ................................................................................. 31 

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8.2.3 
End-of-treatment Visit (Month 3) ............................................................. 32 
8.2.4 
Early Discontinuation Visit ...................................................................... 32 
9 
EFFICACY, SATISFACTION QUESTIONNAIRES, AND SAFETY .............. 33 
9.1 
Efficacy Assessments ............................................................................................... 33 
9.2 
Satisfaction Questionnaires ..................................................................................... 33 
9.3 
Safety Assessments ................................................................................................... 34 
9.3.1 
Safety Definitions ..................................................................................... 35 
9.3.2 
Safety Reporting ....................................................................................... 37 
9.3.3 
AE Assessments ........................................................................................ 38 
9.3.4 
Pregnancy ................................................................................................. 40 
9.3.5 
Laboratory Assessments ........................................................................... 40 
9.3.6 
Other Safety Assessments ......................................................................... 40 
9.4 
Data Safety Monitoring Board ............................................................................... 40 
9.5 
Appropriateness of Measurements ........................................................................ 40 
10 
STATISTICAL METHODS ................................................................................... 40 
10.1 Statistical and Analytical Plans .............................................................................. 40 
10.1.1 
Datasets or Populations Analyzed ............................................................ 40 
10.1.2 
Demographic and Other Baseline Characteristics .................................... 41 
10.1.3 
Efficacy Variables .................................................................................... 41 
10.1.4 
Safety Variables ........................................................................................ 43 
10.1.5 
Handling of Missing Data ......................................................................... 43 
10.2 Determination of Sample Size ................................................................................. 45 
10.3 Protocol Deviations .................................................................................................. 45 
11 
QUALITY ASSURANCE AND QUALITY CONTROL ..................................... 45 
11.1 Audit and Inspection ............................................................................................... 45 
11.2 Monitoring ................................................................................................................ 46 
11.3 Data Management and Coding ............................................................................... 46 
12 
RECORDS AND SUPPLIES .................................................................................. 47 
12.1 Investigational Medical Device Accountability ..................................................... 47 
12.2 Financing and Insurance ......................................................................................... 47 
13 
ETHICS .................................................................................................................... 48 
13.1 Independent Ethics Committee or Institutional Review Board .......................... 48 
13.2 Regulatory Authorities ............................................................................................ 48 
13.3 Ethical Conduct of the Study .................................................................................. 48 
13.4 Informed Consent .................................................................................................... 48 
13.5 Subject Confidentiality ............................................................................................ 49 

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13.6 Reporting and Publication, Including Archiving ................................................. 49 
14 
REFERENCES ........................................................................................................ 50 
15 
APPENDICES .......................................................................................................... 51 
15.1 Centers for Disease Control and Prevention Surgical Site Infection 
Criteria 52 
15.2 Dermabond Advanced Instructions for Use .......................................................... 57 
15.3 Patient and Observer Scar Assessment Scale ....................................................... 60 
15.4 Modified Hollander Cosmesis Scale ....................................................................... 62 
15.5 Product-related Questionnaire for Investigators .................................................. 63 
15.6 Subject-related Questionnaire for Investigators ................................................... 66 
15.7 Subject-completed Questionnaire .......................................................................... 67 
15.8 Contact Information for Safety Reporting ............................................................ 70 
15.9 Investigator Signature Page .................................................................................... 71 
 
 
 

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4 
LIST OF ABBREVIATIONS 
LIST OF ABBREVIATIONS 
ADE 
Adverse device effect 
AE 
Adverse event 
CDC 
Center for Disease Control and Prevention 
CMH 
Cochran-Mantel-Haenszel 
DD 
Device deficiency 
eCRF 
Electronic case report form 
FAS 
Full Analysis Set 
FM 
Farrington-Manning 
GCP 
Good Clinical Practice 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
ID 
Identifier 
IEC 
Independent Ethics Committee 
IMD 
Investigational medicinal device 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
mHCS 
Modified Hollander Cosmesis Scale 
POSAS 
Patient and observer scar assessment scale 
PPS 
Per Protocol Set 
SAE 
Serious adverse effect 
SAP 
Statistical analysis plan 

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5 
INTRODUCTION 
The goal of wound closure is to achieve hemostasis, avoid infection, and restore function to 
the affected skin area with minimal scarring. The most commonly used methods for wound 
closure after surgical procedures or traumatic injuries employ staples or sutures. Alternative 
methods for wound closure include the use of skin adhesives. The application of skin 
adhesives offers potential advantages over standard staple/suture methods (Smith et al. 2010, 
Sajid et al. 2009, Dumville et al. 2014): 

Simpler and shorter application procedure.

Reduced pain intensity.

Less trauma and disruption of wound’s microcirculation.

No painful injection of local anesthetic.

Barrier function against microbial penetration into the wound bed.

No risk of accidental needle stick injury.

No need for follow-up for removal of sutures.

Good cosmetic results.
Adhesives have been used in various forms for many years since the first cyanoacrylate 
adhesives were synthesized (Coover 1959). These early adhesives were appropriate for small 
superficial lacerations and incisions, but their limited physical properties prevented use in the 
management of other wounds. In addition, acute and chronic inflammatory reactions were 
reported to occur (Houston 1969). Further development led to the introduction of the n-2-
butylcyanoacrlyates that were purer and stronger, but those did not receive widespread 
acceptance, because their clinical performance was limited by their low tensile strength and 
brittleness (Bruns 1996; Quinn 1993). More recently, stronger skin adhesives have been 
developed to increase flexibility and reduce toxicity by combining plasticizers and stabilizers 
(Quinn 1997). Skin adhesives have been used primarily in emergency rooms and there is 
increasing support in the literature for their effectiveness in the closure of various traumatic 
lacerations (Dumville et al. 2014, Farion 2002). Surgeons now also use skin adhesives in the 
operating room for the closure of surgical skin incisions. 
Although skin adhesives may offer some of the advantages listed above, a Cochrane 
Systematic Review concluded that there is insufficient evidence as to whether covering 
surgical wounds healing by primary intention with cyanoacrylates adhesives reduces the risk 
of infections, improves scarring, pain control, subject acceptability or ease of dressing 
removal. Apart from that, the review showed that sutures are significantly better than 
cyanoacrylate adhesives for minimizing dehiscence (Dumville et al. 2014). As such, the 
development of a skin adhesive that affords dehiscence comparable with sutures would offer 
subjects an alternative method of wound closure which is less burdensome than the use of 
sutures or staples. 
Wound dehiscence is one of the most common complications of surgical wounds and it 
involves the breaking open of the surgical incision along the suture. Typically, the sutures or 
closures around wound edges stay intact while new tissue, known as "granulation tissue," 
starts forming to help heal the wound. However, when wound dehiscence occurs, the edges 
starts to separate and the wound reopens instead of healing. 

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Wound dehiscence can be caused by poor surgical techniques such as improper suturing, 
overtightened sutures, or inappropriate type of sutures. Wound dehiscence can also be caused 
by increased stress to the wound area as a result of strenuous exercise, heavy lifting, 
coughing, laughing, sneezing, vomiting, or bearing down too hard with a bowel movement. 
In some cases, wound dehiscence could be secondary to wound infection or poor healing as 
seen in patients with chronic diseases, malnutrition, or weak immune systems. Secondary 
wound dehiscence can also occur in patients with AIDS, renal disease, diabetes mellitus, and 
those undergoing chemotherapy or radiotherapy. 
Every person who has a surgical wound has a risk of dehiscence, especially in the first 
2 weeks after surgery when the tissue is still weak and not completely healed. The 2 most 
important factors controlling the risk of wound dehiscence are: 

The patient's health status – the risk is higher in patients with a weak immune system,
malnutrition, or chronic medical illness.

The surgical procedure – the risk of dehiscence increases with overtightening of
sutures, poor suturing technique, inappropriate surgery site, or suturing material.
The risk is also greater with smoking, obesity, premature postsurgery exercise, heavy lifting, 
recurrent vomiting, coughing, or an improper diet that leads to constipation. 
Any wound dehiscence needs to be treated as a new wound and is a surgical emergency that 
requires immediate attention. Surgical debridements, antibiotic therapy, reclosure with the 
appropriate surgical technique, and sutures represent the most appropriate treatments. Finally, 
the patient's wound should be closely monitored to prevent dehiscence from recurring. 
For all the above mentioned reasons, wound dehiscence always needs to be prevented as 
much as possible. 
Therefore, a new, polyurethane-based topical skin adhesive has been developed: 
MAR-CUTIS. MAR-CUTIS is intended for topical application to close wounds of the skin, 
such as cuts and wounds from surgical incisions. It consists of a polyurethane-based 
prepolymer and an amino acid-based hardening agent which are provided in prefilled, double 
syringes with a mixing cannula and spreader tip. 
Information about the preclinical testing as well as known and expected benefits, risks, 
serious adverse events (SAEs) and reasonably anticipated adverse events (AEs) of 
MAR-CUTIS are to be found in the Investigator’s Brochure. 
In particular, there are some predictable AEs (rates) that have been observed with other skin 
adhesives and can be possibly associated with the use of MAR-CUTIS: 
•
Infection (3.6%) after wound closure; this also applies to sutures and is not
limited to adhesives.
•
Dehiscence (2.5%) which is greater in wounds closed with skin adhesive as
compared to other methods of wound closure (namely sutures, staples and
strips).
•
Improper application of the skin adhesive (unknown).

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• 
Allergic reactions (11.5%).  
• 
Other additional risks mentioned in risk management file, eg, pain (6.1%), 
edema (9.7%), and warmth (1.3%). 
Such novel polyurethane-based medical adhesive differs from existing technologies due to its 
unique composition. The adhesive technology is: 
 
Fully Synthetic 
 
Easy to use 
 
Flexible 
Based on polyurethane, it is completely different from existing skin adhesives based on 
cyanoacrylate. This new component is adhering to the tissue via mechanical and physical 
adhesion, forming a strong, yet flexible film. There is no reaction with the tissue itself; a 
strong polymer network is quickly formed and full polymerization is completed after a few 
minutes. 
 

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6 
STUDY OBJECTIVES 
Objectives 
Endpoints 
Primary Efficacy Objective: 
 To compare the dehiscence rate 
between MAR-CUTIS and Dermabond 
Advanced between Day 1 and Day 10.  
Primary Efficacy Endpoint: 
 Total dehiscence rate of target 
incision/laceration assessed at the Day 
10 visit. 
Main safety objective: 
 To compare the incidence of AEs 
between MAR-CUTIS and Dermabond 
Advanced.  
Main safety endpoint: 
 Adverse events within 1 month after 
treatment classified by severity and 
relatedness to the treatment.  
Secondary 
 To compare the dehiscence rate 
between MAR-CUTIS and Dermabond 
Advanced at the Month 1 visit.  
 Total dehiscence rate of target 
incision/laceration assessed at the 
Month 1 or Early Discontinuation visit 
(if Early Discontinuation occurs 
before Month 1). 
 To compare the incidence of AEs 
between MAR-CUTIS and Dermabond 
Advanced at additional study time 
points.  
 Adverse events classified by severity 
and relatedness to the treatment.  
 
 To evaluate the subject satisfaction 
with the cosmetic outcome after 
treatment of the surgical 
incision/laceration with MAR-CUTIS 
versus Dermabond Advanced. 
 Subject-completed Patient and 
Observer Scar Assessment Scale 
(POSAS) done at the Month 1 and 
Month 3 visits or at the Early 
Discontinuation visit (if Early 
Discontinuation occurs before 
Month 1). 
 To compare the wound infection 
incidence between both treatment 
groups. 
 
 
 
 Wound infection incidence assessed at 
the Day 10, Month 1, and Month 3 
visits or at the Early Discontinuation 
visit (diagnosed according to the 
Centers for Disease Control and 
Prevention [CDC] criteria for surgical 
site infection [Section 15.1]). 
 Wound infection assessed on a binary 
scale (“1 - yes” or “0 - no”) for the 
following criteria: 
o Presence of erythema 
o Presence of edema 
o Presence of pain at rest 
o Presence of elevated temperature 
A total score will be calculated for each 
subject.  
 To evaluate the investigator 
satisfaction with the cosmetic outcome 
after the closure of the target surgical 
incision/laceration with MAR-CUTIS 
versus Dermabond Advanced. 
 Investigator-completed POSAS done 
at the Month 1 and Month 3 visits or 
at the Early Discontinuation visit (if 
Early Discontinuation occurs before 
Month 1). 

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 Investigator-completed Modified 
Hollander Cosmesis Scale (mHCS) 
done at the Day 10 and Month 1 visits 
or at the Early Discontinuation visit (if 
Early Discontinuation occurs before 
Month 1). 
 To evaluate the subject comfort with 
the device during and after treatment 
with MAR-CUTIS versus Dermabond 
Advanced. 
 A questionnaire related to subject 
experience and satisfaction with the 
device completed by the subject at the 
Day 10 and Month 1 visits or at the 
Early Discontinuation visit (if Early 
Discontinuation occurs before Month 
1). 
 A subject-related questionnaire 
completed by the investigator at the 
Day 0 and Month 1 visits or at the 
Early Discontinuation visit (if Early 
Discontinuation occurs before Month 
1). 
 To evaluate the investigator overall 
satisfaction and ease of use with the 
device during and after the closure of 
the target surgical incision/laceration 
with MAR-CUTIS or Dermabond 
Advanced. 
 A product-related questionnaire 
completed by investigators at the 
Month 1 or Early Discontinuation visit 
(if Early Discontinuation occurs 
before Month 1). 
 

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7 
INVESTIGATIONAL PLAN 
7.1 
Overall Study Design and Plan: Description 
This is a randomized, open-label, multi-center, comparator-controlled clinical study to 
compare MAR-CUTIS with Dermabond Advanced in closure of surgical incisions ≥6 to 
≤15 cm and lacerations ≤15 cm. A total of 189 subjects will be treated (defined as study 
product applied to the wound). Only subjects that are withdrawn from the study due to 
product failure at the time of application (see Section 7.3.4) will be replaced. Subjects will be 
randomized 2:1 to MAR-CUTIS or Dermabond Advanced. Screening and baseline 
(randomization) can occur on the same day. Application of the investigational medical device 
(IMD) occurs on Day 0 with wound evaluation occurring on Day 1, Day 10, Month 1, and 
Month 3/Early Discontinuation. Training on the application of both devices will be provided. 
7.1.1 Study Design 
Figure 8.1 
Study Design 
 
 

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7.1.2 Schedule of Assessments 
 
D -21 to 0 
D0 
D1 
D10 
Month 1 
Month 3 
ED 
Visit Window 
 
 
12 hours up to 36 hours 
after application 
±2 days 
±7 days 
±14 days 
 
Obtain written informed consent/assent 
X 
 
 
 
 
 
 
Check inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
Record demographic data and medical/surgical historya 
X 
 
 
 
 
 
 
Perform a urine ß-hCG pregnancy test (if applicable) 
 
X 
 
 
 
 
 
Allocate subject to treatment and issue a diary 
 
X 
 
 
 
 
 
Application of device 
 
X 
 
 
 
 
 
Document prior (within the last 2 weeks) and 
concomitant medication intake (including steroids, 
immunosuppressants, chemotherapy, anticoagulants, 
antibiotics. Excluding related to intraoperative 
anesthesia) 
X 
X 
X 
X 
X 
X 
X 
Record of adverse events 
X 
X 
X 
X 
X 
X 
X 
Record of incidents and device performance, 
device-related complaints 
 
X 
X 
X 
X 
X 
X 
Evaluation of incision/laceration (incidence and grading) 
 
X 
 
 
 
 
 
Evaluation of dehiscence  
 
 
X 
X 
X 
 
Xd 
Evaluation of wound infection  
 
 
 
X 
X 
X 
X 
mHCS completed by investigator 
 
 
 
X 
X 
 
Xd 
POSAS completed by subject and investigator  
 
 
 
 
X 
X 
Xd 
Subject-completed satisfaction questionnaire 
 
 
 
X 
X 
 
Xd 
Subject-related questionnaire completed by investigatorc 
 
X 
 
 
X 
 
Xd 
Product-related questionnaire completed by investigator 
 
 
 
 
Xb 
 
Xd 
Subject diary collection 
 
 
 
 
X 
 
Xd 
Abbreviations: ß-hCG=beta human chorionic gonadotropin; D=Day; ED=early discontinuation; mHCS= Modified Hollander Cosmesis Scale; POSAS= Patient and Observer 
Scar Assessment Scale. 
. 

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a In particular, the following information will be collected: body mass index, medical history (including diabetes mellitus, chronic obstructive pulmonary disorder, 
hematological and vascular disorders, disorders of immune system, congestive heart failure, cardiovascular disease), concomitant medications (excluding related to 
intraoperative anesthesia), smoking, alcohol abuse. 
b The product-related questionnaire is completed by the investigator only once per site when the last subject randomized at the site completes the Month 1 visit. 
c Also completed if there is premature removal of the adhesive. 
d Only to be performed if Early Discontinuation is before the Month 1 Visit or if the questionnaire has not previously been completed/if the diary has not previously been 
collected. 

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7.2 
Discussion of Study Design 
7.2.1 Study Design 
The study will include 3 levels of stratification: 
 By wound type (lacerations and incisions): approximately 40 subjects with lacerations 
will be randomized. 
 By skin type according to the Fitzpatrick classification (types I to III versus types IV 
to VI): approximately 40 subjects with skin types IV to VI will be randomized; 
approximately 20 subjects from this cohort will have skin types V to VI. 
 By age group (2 to 21 years of age and ≥22 years of age): approximately 30 subjects 
in the 2 to 21 age group will be randomized.  To ensure that the pediatric population is 
not dominated by an adolescent sub-group, approximately 5 subjects aged 15 to 
<22 years will be included.  
Screening and Randomization 
Only one incision/laceration will be treated with the IMD. If a subject has more than one 
incision/laceration, the target wound will be the one with the greatest length (ie, the longest) 
that meets the study entry criteria. If the length of 2 or more wounds is equal, the investigator 
can chose either of them to be the target wound.  
The incision/laceration will be prepared for closure as per the standard of care at a treating 
hospital. The investigator will assess the need and perform closure of deep tissue layers as 
necessary before proceeding with the closure of the last (dermal) layer with the IMD. 
All lacerations will first be assessed for the need of deep suturing and/or debridement; this 
information will be recorded in the electronic case report form (eCRF). Wounds that require 
debridement and/or deep suturing will be treated according to the local practice of the 
investigator and only at the time of skin closure will the lacerations be randomized into 1 of 
the 2 study treatment arms. Wounds that do not require deep suturing and/or debridement will 
be randomized immediately. 
Re-screening is not allowed in the study. 
Treatment Phase 
Use of Dermabond Advance will be according to Instructions for Use (Section 15.2). Wounds 
closed with Dermabond Advanced will be prepared in a standard manner. They will be 
cleaned with an antiseptic solution (which will be recorded in the eCRF), patted dry with dry, 
sterile gauze, and hemostasis will need to be achieved prior to wound closure (eg, by pressure 
application or use of local vasoconstrictors). Wound edges will be approximated by fingers of 
forceps and Dermabond Advanced will be applied in one continuous layer onto a dry wound 
through painting motions, taking care not to apply adhesive between the wound edges. 
Applying a second layer is not required or recommended. If a second layer of Dermabond 
Advanced is applied, or if large droplets of liquid are not spread thinly, the subject may 
experience an increased sensation of heat or discomfort. The wound will be held for 60 
seconds to allow for complete polymerization. The wound may or may not be covered with a 
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Wounds closed with MAR-CUTIS will be prepared in a standard manner. They will be 
cleansed with an antiseptic solution (which will be recorded in the eCRF), patted dry with 
dry, sterile gauze, and hemostasis will need to be achieved prior to wound closure (eg, by 
pressure application or use of local vasoconstrictors). The use of peroxide-containing 
antiseptics is not recommended to be applied directly on the MAR-CUTIS strip as they may 
provoke cracking of the strip. These products however may be used for preparing the wound 
for closure. In addition, iodine-containing products may be used as necessary but they may 
stain the glue strip making it non-transparent. Wound edges will be approximated by fingers 
of forceps and MAR-CUTIS will be applied in one 1 to 2 mm thick layer ensuring that at 
least 1 cm of the glue is applied over the length of the wound on each side. The amount of the 
glue applied will be calculated such that one 5-mL syringe covers up to 8 cm of wound length 
(giving a total of 10 cm per syringe). For wounds >8 cm, 2 syringes will be needed. The 
wound will be held for approximately 30 seconds to allow for initial polymerization. Only for 
the pediatric population, the maximum number of syringes per day is limited based on the 
body weight as shown in the table below: 
Body Weight 
Number of  MAR-CUTIS Syringes  
10 to <15 kg 
Maximum of 1 syringe 
15 kg and above 
Maximum of 2 syringes 
 
A protective dressing may be applied after 3 minutes and instructions will be given to the 
subject on wound protection and showering as MAR-CUTIS requires moisture protection 
during showering. 
If necessary, further dressing and wound management will be performed in accordance with 
the local practice. 
Evaluation of all wounds will occur on Day 1, Day 10, Month 1, and Month 3/Early 
Discontinuation. 
All subjects (or subject legal guardians in case of a pediatric subject) will be issued a 
subject’s diary to record any wound exposure to water and any complaints. The diaries will 
be collected at the Month 1 study visit and analyzed descriptively. 
7.3 
Selection of Study Population 
The study population will include subjects with surgical incisions from ≥6 to ≤15 cm or 
lacerations ≤15 cm who meet the criteria specified below. 
7.3.1 Number of Planned Subjects 
A total of 189 subjects will be treated (defined as study product applied to the wound). Only 
subjects that are withdrawn from the study due to product failure at the time of application 
(see Section 7.3.4) will be replaced. 
7.3.2 Inclusion Criteria 
For subjects with surgical incisions: 

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1. Subject undergoing closure of surgical incision ≥6 to ≤15 cm following a laparotomy, 
abdominal hysterectomy, inguinal hernia repair, or laparoscopic intervention. 
For subjects with lacerations: 
2. Subject requiring closure of a laceration on face (avoiding the immediate area around 
the eye or lips/mouth) or extremities, ≤15 cm. In subjects with multiple lacerations, 
one will be selected as the target wound (ie, greatest length and meets the study entry 
criteria).  
For all subjects: 
3. Subject has the ability to consent and has given written informed consent/assent to 
participate. 
4. Male and female subjects ≥2 years of age and body weight ≥10 kg.  
5. Subject willing and capable of following instructions for wound care provided by the 
investigator and agreeing to return for all treatment control visits specified in this 
clinical study. 
7.3.3 Exclusion Criteria 
Subjects will be excluded from the study if one or more of the following criterion is 
applicable: 
For subjects with lacerations: 
1. Wounds on mucosal surfaces or across mucocutaneous junctions (eg, oral cavity, lips, 
eyes). 
2. Wounds which may be regularly exposed to body fluids or with dense natural hair 
(eg, scalp); wounds on ears. 
3. Wounds on palms and feet. 
4. Animal or human bites. 
5. Lacerations that are heavily contaminated. 
6. Punctured or crushed wounds. 
7. Subjects with lacerations having wound treatment >6 hours after the trauma. 
For all subjects: 
8. Subjects requiring suturing with sutures >0.5 mm thickness. 
9. Subject with documented skin disease or skin conditions (eg, excessive hair at the site 
of surgery, scar tissue, wound, tattoo, coloration, or pre-existing open sores at the site 
of surgery that would interfere with the application of IMD or the skin assessment, as 
judged by the investigator). 
10. Subject with any factors that may have an adverse effect on wound healing (eg, 
previous history of keloid formation or hypertrophy [including family history]), other 
general risk factors for dehiscence (need of premature post-surgery exercise/heavy 

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lifting, expected conditions leading to recurrent vomiting, coughing, or constipation), 
history of immunosuppression, chronic systemic infection, or poor general health. 
11. Subjects with known blood clotting disorders. 
12. Subjects receiving chronic, pre-operative steroids, immunosuppressants, 
chemotherapy, or anticoagulants; only chronic anti-platelet therapies like 
acetylsalicylic acid (ASA) and clopidogrel are accepted. Chronic is to be interpreted 
as long term or “for more than acute treatment”. Pre-operative standard of care, like a 
single dose of an anticoagulant, for the aforementioned treatments is allowed along 
with standard of care post-operative anticoagulant and chemotherapy regimen 
including application of steroids and immunosuppressants. 
13. Subject having known or suspected allergy or sensitivity to polyurethane, 
cyanoacrylates, formaldehyde, tapes or adhesives, or benzalkonium chloride. 
14. Subject participating in any current clinical study with a non-Conformité 
Européenne–marked device or investigational product. 
15. Subject who is pregnant or breastfeeding. 
16. Subject with history of a significant dermatologic disease or condition, such as atopic 
dermatitis, psoriasis, lichen ruber planus, vitiligo or conditions known to alter the skin 
appearance or physiologic response (eg, decompensated diabetes mellitus, porphyria) 
that involves the investigative site. 
7.3.4 Removal of Subjects From Therapy or Assessments 
Subjects may stop the study for any of the following reasons: 
 Subject request 
 Use of nonpermitted concurrent therapy 
 Lost to follow-up (considered lost to follow-up only before Day 10) 
 Occurrence of AEs not compatible with the continuation of subject participation in the 
study, in the investigator’s opinion, or unacceptable to the subject to continue 
 Investigator request 
 Intercurrent illness 
Subjects are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The reason(s) for withdrawal will be 
documented in the eCRF. 
Subjects withdrawing from the study will be encouraged to complete the same final 
evaluations as subjects completing the study according to this protocol, particularly safety 
evaluations. The aim is to record data in the same way as for subjects who completed the 
study. 
Reasonable efforts will be made to contact subjects who are lost to follow-up. These efforts 
must be documented in the subject’s file. 

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The sponsor has the right to terminate the study at any time in case of SAEs or if special 
circumstances concerning the IMD or the company itself occur, making further treatment of 
subjects impossible. In this event, the investigator(s) will be informed of the reason for study 
termination. 
Removal of Subjects Based on Device Performance 
Subjects will be withdrawn from the study if the adhesive does not adhere appropriately at 
the time of application as assessed by the investigator and the event will be reported as device 
deficiency. 
Pregnancy 
Subjects will be instructed that known or suspected pregnancy occurring during the study, in 
subjects or female partners of male subjects, should be confirmed and reported to the 
investigator. The investigator should also be notified of pregnancy occurring during the study 
but confirmed after completion of the study. In the event that a subject is subsequently found 
to be pregnant after inclusion in the study, the pregnancy will be followed to term and the 
status of mother and child will be reported to the sponsor after delivery. 
Full details will be recorded on the withdrawal page of the eCRF and a pregnancy report will 
be completed. 
7.4 
Investigational Medical Device 
7.4.1 Investigational Medical Device Applied 
MAR-CUTIS is a polyurethane-based skin adhesive. At the time of use, the 2 components in 
the syringe are mixed in the mixing cannula. Complete hardening occurs about 5 minutes 
after application to the skin. The adhesive result can be corrected in the first 30 seconds. 
MAR-CUTIS is distributed sterile and is intended for single use. The product is used for 
topical closure of incisions and surgical wounds, replacing the last dermal suture line. It is not 
intended for intra-abdominal use and/or as a substitute for subcutaneous sutures. It should not 
be used after the expiration date and/or if the sterile packaging has been opened or damaged. 
Dermabond Advanced is a topical skin adhesive used to hold closed easily approximated skin 
edges of wounds from surgical incisions, including incisions from minimally invasive 
surgery, and simple, thoroughly cleansed, trauma-induced lacerations. 
7.4.2 Identity of Investigational Medical Device 
The prepolymer component of MAR-CUTIS is made with hexamethylene diisocyanate, 
benzoyl chloride, and trifunctional polyol with primarily short alkylene oxide units. The 
curing agent is composed of diethyl maleate, 1,5-diamino-2-methylpentane, and polyethylene 
glycol 200. MAR-CUTIS should be stored at room temperature (15 to 25°C) and should be 
protected from moisture and humidity. 
The active ingredient in Dermabond Advanced is 2-octyl cyanoacrylate. The recommended 
storage conditions are below 30°C (86°F), and away from moisture, direct heat, and direct 
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7.4.3 Manufacturing, Packaging, and Labeling 
Manufacturing, labeling, packaging, and shipment of MAR-CUTIS will be performed by 
Syneos Health. All manufacturing, packaging, and labeling operations will be performed 
according to Good Manufacturing Practice for Medicinal Products and the relevant regulatory 
requirements. Details of packaging and labeling will be on file in the trial master file. 
Dermabond Advanced adhesive is supplied sterile, in a prefilled, single-use applicator. The 
pen-style applicator consists of a crushable ampoule contained within a plastic applicator. 
The applicator contains the liquid adhesive. The applicator is supplied in a blister package to 
maintain the sterility of the device until opened or damaged. Dermabond Advanced adhesive 
is available in boxes of 6 or 12 applicators. 
7.4.4 Method of Assigning Subjects to Treatment Groups 
Subjects (ie, the unique subject identifier [ID] consisting of center ID and subject ID) will be 
randomly allocated to treatment according to a randomization scheme designed using the 
covariate-adjusted dynamic allocation method as implemented in Balance (Medidata, 2015). 
The algorithm combines complete randomness with a minimization method (Pocock and 
Simon, 1975), not only looking at marginal balances, but also considering the treatment 
balances overall and within individual strata, to ensure a balanced treatment allocation. Based 
on the expected clinical relevance of the explanatory variables for incision and laceration 
closure, the algorithm is implemented by assigning a different weight to the stratification 
factors to be included in the trial and minimize unbalances (ie, wound type having more 
importance than the other 2 factors, and age group having more importance than skin type). 
Further details regarding the parameters used to implement the randomization in balance are 
documented in the form “Balance Study Configuration Requirements”.  
The incision/laceration will be prepared for closure as per the standard of care at a treating 
hospital. The investigator will assess the need and perform closure of deep tissue layers as 
necessary before proceeding with the randomization and subsequently with the closure of the 
last (dermal) layer with the IMD. 
Eligible subjects will be randomized 2:1 to MAR-CUTIS or Dermabond Advanced. 
 
The study will include 3 levels of stratification as randomization factors: 
 By wound type (lacerations and incisions). 
 By skin type according to the Fitzpatrick classification (types I to III versus types 
IV to VI). 
 By age group (aged 2 to 21 years and ≥22 years).  
The primary efficacy analysis will consider the stratification factors as explanatory variables 
in the model. Additionally, center will be considered as a further randomization factor as 
recommended by International Council for Harmonisation (ICH) E9. 
 
7.4.5 Application in the Study 
Detailed instruction and a training video on the application of MAR-CUTIS will be provided 
to each investigational site. MAR-CUTIS will be applied in one 1 to 2 mm thick layer, 
ensuring that at least 1 cm of the glue is applied over the length of the wound on each side. 

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The amount of the glue applied will be calculated such that one 5-mL syringe covers 
approximately 8 cm of wound length (giving a total of 10 cm per syringe). For wounds >8 
cm, 2 syringes will be required. The wound will be held for approximately 30 seconds to 
allow for initial polymerization. Only for the pediatric population, the maximum number of 
syringes per day is limited based on the body weight as shown in the table below: 
Body Weight 
Number of MAR-CUTIS Syringes  
10 to <15 kg 
Maximum of 1 syringe 
15 kg and above 
Maximum of 2 syringes 
 
Detailed instruction and a training video on Dermabond Advanced application will also be 
provided to each investigational site. Use of Dermabond Advanced will be according to 
Instructions for Use (Section 15.2). Dermabond Advanced will be applied in one continuous 
layer onto a dry wound through painting motions, taking care not to apply adhesive between 
the wound edges. Applying a second layer is not required or recommended. If a second layer 
of Dermabond Advanced is applied or if large droplets of liquid are not spread thinly, the 
subject may experience an increased sensation of heat or discomfort. The wound will be held 
for 60 seconds to allow for complete polymerization. 
7.4.6 Timing of Application for Each Subject 
The IMD will be applied only on Day 0 as instructed in Section 7.4.5. 
7.4.7 Blinding 
Blinding is not applicable as this is an open-label study. 
In the given context, a blinding of investigators, site staff, and subjects is not feasible due to 
visual differences between the two adhesives, and therefore the possibility to distinguish both 
products. The assessment of the dehiscence and other endpoints might be prone to bias given 
the open-label trial design. To minimize the potential bias, sites will provide adequate 
training to all device users and further site staff involved in the trial in cooperation with the 
Sponsor. 
7.4.8 Prior and Concomitant Therapy 
Medication taken within the two weeks before screening will be documented in the eCRF. 
Allowed medications include those not listed in Section 7.4.8.1. Intraoperative anesthesia is 
not considered concomitant medication and does not require capturing in the eCRF. 
7.4.8.1 Prohibited Medication/Therapy 
Prohibited medications are chronic, pre-operative steroids, immunosuppressants, 
chemotherapy, and anticoagulants; only chronic anti-platelet therapies like acetylsalicylic 
acid (ASA) and clopidogrel are accepted. Chronic is to be interpreted as long term or “for 
more than acute treatment”. Pre-operative standard of care, like a single dose of an 
anticoagulant, for the aforementioned treatments is allowed along with standard of care post-
operative anticoagulant and chemotherapy regimen including application of steroids and 
immunosuppressants. 

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7.4.8.2 Rescue Medication 
Not applicable. 
7.4.9 Treatment Compliance 
The IMD will only be applied on Day 0 by the investigator. The timing of the glue 
detachment will be noted and recorded in the eCRF (day of application). Early glue removal 
and reason for removal will also be recorded in the eCRF. 
7.4.10 Device Deficiencies Reporting 
Device deficiencies (complaints and malfunctions) will be recorded in the subject diary. The 
investigator shall record all observed device deficiencies together with an assessment in the 
eCRF. If the device deficiency leads to an SAE, an SAE form must also be completed (see 
Section 9.3.2). 
The Sponsor will ensure that the device can be inspected for defects in the event of 
procedural complications and root cause analysis will be done. 
8 
TIMING OF STUDY PROCEDURES 
Subjects/legal guardians will provide written informed consent/assent before any 
study-related procedures are performed. The planned study assessments are in Section 7.1.2. 
8.1 
Treatment 
8.1.1 Screening Visit (Day -21 to 0) 
 Review and sign informed consent/assent form. 
 Assess for eligibility (against the inclusion and exclusion criteria). 
 Collect medical and surgical history (including diabetes mellitus, chronic obstructive 
pulmonary disease, hematological and vascular disorders, disorders of immune 
system, congestive heart failure, cardiovascular disease, smoking, and alcohol abuse). 
 Record demographic data, such as ethnic origin, race, age, and sex. 
 Record prior and concomitant medication (including steroids, immunosuppressants, 
chemotherapy, anticoagulants, and antibiotics. Excluding related to intraoperative 
anesthesia). 
 Record adverse events (if applicable and if not recorded as medical history). 
 
8.1.2 Baseline Visit (Day 0) 
Screening and baseline can occur on the same day. The following procedures will be 
performed at the Baseline Visit: 
 Reassess for eligibility against the inclusion and exclusion criteria if baseline is not on 
the same day as screening. 
 Record concomitant medication (Excluding related to intraoperative anesthesia). 

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 Record adverse events. 
 Record of incidents and device performance, device-related complaints 
 Perform a urine beta-human chorionic gonadotropin (ß-HCG) pregnancy test (in all 
female subjects of childbearing potential [post-menarchal and pre-menopausal]). 
 Issue a subject diary. 
 Subject-related questionnaire completed by investigator. 
 Evaluation of incision/laceration (incidence and grading). 
When all the baseline procedures have been performed, subjects will be randomized (the 3 
stratification factors of age group, wound type, and skin type will be recorded). All wounds, 
including those that require debridement and/or deep suturing, will be prepared for closure as 
per the standard of care at a treating hospital. The investigator will assess the need and 
perform closure of deep tissue layers as necessary before proceeding with the closure of the 
last (dermal) layer with the IMD. Once the IMD has been applied to the wound, the 
investigator will complete the specified portion of the subject-related questionnaire. 
 
8.2 
Follow-up Period 
Subjects treated for lacerations may not be able to attend the Day 1 visit since they are 
usually not hospitalized. In this case, all attempts should be made to obtain information on 
potential dehiscence and AEs by phone. The reason for non-attendance should also be 
reported. 
In case a subject is not able to attend the Day 10 visit, a telephone call can be done to capture 
the primary endpoint variables information. However, this is only allowed for exceptional 
cases and the reason for non-attendance and potential dehiscence and AEs should be 
recorded. 
8.2.1 Day 1 
The following procedures will be performed at Day 1: 
 Record concomitant medication. 
 Record AEs. 
 Record of incidents and device performance, device-related complaints. 
 Evaluation of dehiscence (incidence and grading). 
8.2.2 Day 10 and Month 1 
The product-related questionnaire will be completed by the investigator only once per site 
when the last subject randomized at the site completes the Month 1 visit. 
The following procedures will be performed at both Day 10 and Month 1: 
 Record concomitant medication 
 Record AEs 
 Record of incidents and device performance, device-related complaints 

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 Evaluation of dehiscence (incidence and grading) 
 Evaluation of wound infection, if an infection occurred (incidence and criteria score) 
 Modified Hollander Cosmesis Scale (mHCS) completed by investigator 
 Subject-completed satisfaction questionnaire  
Additional procedures performed at Month 1 include: 
 Patient and Observer Scar Assessment Scale (POSAS), completed by subject and 
investigator 
 Subject-related questionnaire completed by investigator 
 Collect subject diary 
 
8.2.3 End-of-treatment Visit (Month 3)  
The following procedures will be performed at the Month 3 visit: 
 Record concomitant medication 
 Record AEs 
 Record of incidents and device performance, device-related complaints 
 Evaluation of wound infection, if an infection occurred (incidence and criteria score) 
 Patient and Observer Scar Assessment Scale completed by subject and investigator 
8.2.4 Early Discontinuation Visit 
The following procedures will be performed at the Early Discontinuation Visit: 
 Record concomitant medication 
 Record AEs 
 Record of incidents and device performance, device-related complaints 
 Evaluation of wound infection, if an infection occurred (incidence and criteria score) 
 Patient and Observer Scar Assessment Scale completed by subject and investigator 
 Subject-completed satisfaction questionnaire (completed if Early Discontinuation is 
before the Month 1 visit or if the questionnaire has not previously been completed) 
 Modified Hollander Cosmesis Scale (mHCS) completed by investigator (completed if 
Early Discontinuation is before the Month 1 visit or if the questionnaire has not 
previously been completed) 
 Subject-related questionnaire completed by investigator (completed if Early 
Discontinuation is before the Month 1 visit or if the questionnaire has not previously 
been completed) 
 Product-related questionnaire completed by the investigator (completed if Early 
Discontinuation is before the Month 1 visit or if the questionnaire has not previously 
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 Evaluation of dehiscence (completed if Early Discontinuation is before the Month 1 
visit) 
 Collection of subject diary (collected if the diary has not previously been collected) 
 
The overall study duration for each subject is up to 4 months. 
 
9 
EFFICACY, SATISFACTION QUESTIONNAIRES, AND SAFETY 
The planned schedule of assessments is in Section 7.1.2. 
9.1 
Efficacy Assessments 
 Total dehiscence rate assessed at the Day 1, Day 10, Month 1, and Early 
Discontinuation (if earlier than Month 1) study visits. 
 Classification of dehiscence: 
o Partial dehiscence not requiring re-treatment; 
o Dehiscence to original depth/length not  requiring re-treatment (eg, closure with 
secondary intention); 
o Any dehiscence requiring re-treatment  (including draining, debridement, 
closure,  management of infection, etc.). 
 Classification of dehiscence according to their grade (World Union of Wound Healing 
Societies Scale): 
o Dermal layer only 
o Subcutaneous layer exposed, fascia not visible 
o Subcutaneous layer and fascia exposed 
o Any area of fascial dehiscence with organ space, viscera or bone exposed 
9.2 
Satisfaction Questionnaires 
 Patient and Observer Scar Assessment Scale (Section 15.3) will be completed by the 
subject and investigator at the Month 1 and Month 3 visits or the Early 
Discontinuation visit (Section 7.1.2). 
o The POSAS is a questionnaire that was developed to assess scar quality. It 
consists of 2 separate 6-item scales (Observer Scale and Patient Scale), both of 
which are scored on a 10-point rating scale. 
o Each scale has an overall “opinion” with 1 being no pain, no itching, or 
normal skin and 10 being worst scar imaginable with pain and itching. 
 Modified Hollander Cosmesis Scale (Section 15.4) is completed by investigator at the 
Day 10, Month 1, and Early Discontinuation (if earlier than Month 1 or if the 
questionnaire has not previously been completed) visits (Section 7.1.2). 
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o Each of the characteristics is graded on a 0 (no/good) or l (yes/poor) point 
scale. A total cosmetic score is derived by the addition of the scores.  
 One product-related questionnaire for investigators (Section 15.5) will be completed 
for each site when the last randomized subject at the site completes the Month 1 visit 
(Section 7.1.2). This questionnaire will be completed at the Early Discontinuation 
visit if the visit is earlier than the Month 1 visit or if the questionnaire has not 
previously been completed. 
o This questionnaire consists of 8 yes/no questions and 1 opinion question that 
evaluate the investigator’s experience with use of the adhesive (ie, instructions 
easy to understand, preparation of the syringe being easy and fast, glue 
hardening time). 
 Subject-related questionnaire completed by investigators (Section 15.6) will be done 
at the Day 0, Month 1, and Early Discontinuation (if earlier than Month 1 or if the 
questionnaire has not previously been completed) visits and if there is premature 
removal of the adhesive (Section 7.1.2). 
o This questionnaire consists of 5 yes/no questions that assess the investigator’s 
experience applying the adhesive (ie, easy to use, fast, without complications), 
a visual analog scale that rates usability of the product from 1 to 100, and 
1 question that evaluates satisfaction with the adhesive. The questions are 
categorized into 3 sections, each section to be completed at different visits. 
 A subject-completed questionnaire (Section 15.7) will be done at the Day 10, 
Month 1, and Early Discontinuation (if earlier than Month 1 or if the questionnaire 
has not previously been completed) visits (Section 7.1.2). 
o The questionnaire at the Day 10 visit consists of 5 yes/no questions that 
evaluate the subject’s experience with the adhesive, 1 question that rates the 
effect of the closed wound on several daily activities (ie showering, getting 
dressed), 1 question that evaluates satisfaction with the wound closure, and 
visual analog scales which rate pain on a scale of 1 to 10. 
o The questionnaire at the Month 1 visit consists of 3 questions including a 
visual analog scale which rates pain on a scale of 1 to 10, and 2 questions 
relating to the subject’s overall satisfaction with the wound closure. 
Note: For children, parents or legal guardians may assist in the completion of the 
questionnaires. 
9.3 
Safety Assessments 
 Adverse events. 
 Wound infection incidence assessed at the Day 10, Month 1, and Month 3/Early 
Discontinuation study visits (diagnosed according to the Centers for Disease Control 
and Prevention [CDC] criteria for surgical site infection). 
 Wound infection assessed on a binary scale (“1 - yes” or “0 - no”) for the following 
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o Presence of erythema 
o Presence of edema 
o Presence of pain at rest 
o Presence of elevated temperature at target wound area 
9.3.1 Safety Definitions 
Adverse Event 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical 
signs (including an abnormal laboratory finding) in subjects, users or other persons whether 
or not related to the IMD. 
This includes events related to the IMD or the comparator. This includes events related to the 
procedures involved (any procedure in the clinical investigation plan). For users or other 
persons this is restricted to events related to the IMD. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of IMD, whether 
or not it is related to the IMD. This includes an exacerbation of pre-existing conditions or 
events, intercurrent illnesses, or the significant worsening of the indication under 
investigation that is not recorded elsewhere in the eCRF under specific efficacy assessments. 
Anticipated fluctuations of pre-existing conditions, including the disease under study that do 
not represent a clinically significant exacerbation or worsening need not be considered AEs. 
Adverse Device Effect 
Adverse event related to the use of an IMD. 
This includes any AE resulting from insufficiencies or inadequacies in the Instructions for 
Use, the deployment, the implantation, the installation, the operation, or any malfunction of 
the IMD. This includes any event that is a result of a use error or intentional misuse. 
Device Deficiency 
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 DDs related to the identity, quality, durability, reliability, safety or performance of an 
IMD shall be documented throughout the clinical investigation and appropriately managed by 
the sponsor. 
Device deficiencies that did not lead to an AE but could have led to a medical occurrence:  
 If either suitable action had not been taken, 
 If intervention had not been made, or 
 If circumstances had been less fortunate, shall be reported to regulatory authorities 
and ethic committees, as required by the national regulations. 

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Serious Adverse Event 
An SAE is any untoward medical occurrence or effect that: 
 Led to death, or 
 Led to serious deterioration in the health of the subject, that either resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient or prolonged hospitalization, or 
o medical or surgical intervention to prevent life-threatening illness or injury or 
permanent, or 
o impairment to a body structure or a body function. 
 Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
This includes DDs that might have led to an SAE: 
 if suitable action had not been taken, or  
 if intervention had not been made, or  
 if circumstances had been less fortunate.  
These are handled under the SAE reporting system. 
Planned hospitalization for a pre-existing condition, or a procedure required by the protocol, 
without a serious deterioration in health, is not considered an SAE. Important medical 
reactions that may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above should also be considered serious. 
 
The term “life-threatening”, in the definition, refers to an event in which the subject is at risk 
of death at the time of the event; it does not refer to an event which hypothetically might have 
caused death if it would have been more severe. 
In addition, medical and scientific judgement is required to decide if prompt notification is 
required in situations other than those defined for SAEs above. This may include any event 
that the investigator regards as serious that did not strictly meet the criteria above but may 
have jeopardized the subject or required intervention to prevent one of the outcomes listed 
above, or that would suggest any significant hazard, contraindication, side effect, or 
precaution that may be associated with the use of the investigational product. 
Serious Adverse Device Effect 
An adverse device effect (ADE) that has resulted in any of the consequences characteristic of 
an SAE. 
Unanticipated Serious Adverse Device Effect 
Serious ADE which by its nature, incidence, severity or outcome has not been identified in 
the current version of the MAR-CUTIS risk analysis report or Instructions for Use for 
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 Anticipated: an effect which by its nature, incidence, severity or outcome has been 
previously identified in applicable product information (risk analysis report, 
Instruction for use). 
9.3.2 Safety Reporting 
9.3.2.1 Documentation and Reporting of Adverse Events 
Adverse events should be reported and documented in accordance with the procedures 
outlined below. All AEs occurring during the study must be documented on the relevant 
eCRF pages. The following data should be documented for each AE: 
 Description of the symptom event 
 Classification of ‘serious’ or ‘not serious’ 
 Severity 
 Date of first occurrence and date of resolution (if applicable) 
 Action taken 
 Causal relationship 
 Outcome of event (unknown, recovered, not yet recovered, recovered with sequelae, 
death [with date and cause reported]) 
The investigator will record all AEs from the time following the signature of informed 
consent/assent until the last visit of the subject or later in case of ongoing AEs. 
It is the responsibility of the investigator to document all AEs that occur during the study. 
Adverse events may be directly observed, evident in laboratory or diagnostic results, reported 
spontaneously by the subject, or by questioning the subject at each study visit. Subjects 
should be questioned in a general way, without directly prompting about the occurrence of 
any specific symptoms (eg, “How have you been feeling since the last visit?”). Adverse 
events should be reported on the appropriate page of the eCRF. 
9.3.2.2 Reporting of Serious Adverse Events 
From the signature of informed consent/assent until the last visit of the subject, the 
investigator must notify Syneos Health of the following events immediately (within 24 hours 
of the investigator becoming aware of the event) regardless of their causality: 
 Any SAE 
 Any DD 
 New findings/updates in relation to already reported events 
Serious AEs occurring in or to subjects that are in the comparator arm of an investigation 
shall also be reported in accordance with the SAE reporting system. 
This initial notification is the object of the SAE/DD form reported by e-mail or by fax (see 
Section 15.8). The investigator will be requested to supply as much detailed information 
regarding the event that is available at the time of the initial contact (examinations carried 
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The investigator is also required to submit follow-up reports as soon as possible, including 
additional information such as diagnosis, outcome, causality assessment, results of specific 
investigations, and any new significant information that has not been previously reported. 
Copies of additional laboratory tests, consultation reports, post mortem reports, hospital case 
reports, autopsy reports, and other documents should be sent when requested and applicable. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the investigator at any 
time after cessation of study device administration and linked by the investigator to this 
study, should be reported to the study monitor. The sponsor and/or Syneos Health will 
promptly notify all relevant safety information to the competent authorities, central Ethics 
Committees and investigators according to the local, national specific, safety reporting 
requirements and timelines in compliance with the required deadlines, and in accordance with 
European Union medical device directives and medical device guidelines: MEDDEV 2.7/3 
rev 3. The same notification process and reporting timelines will apply for all products 
involved in the study. This also applies to the reporting of any new safety information which 
may modify significantly the benefit risk ratio of an investigational product or which may 
lead to modification of the conditions of use of the investigational product. 
Details of the procedures to be followed if a pregnancy occurs are provided in Section 7.3.4. 
9.3.2.3 Follow-up of Adverse Events 
All investigators should follow-up with subjects with AEs/ADEs/SAEs until the event is 
resolved or until, in the opinion of the investigator, the event is stabilized or determined to be 
chronic. Details of AE resolution must be documented in the eCRF. If the AE extends beyond 
the end of the study, it will be followed until resolution although the study will proceed with 
close-out activities independently. 
Subjects should be followed-up by the end of study visit (Month 3/Early Discontinuation), 
and any AEs/ADEs/SAEs/DDs that occur during this time should be reported according to 
the procedures outlined above. 
For all SAEs, where important or relevant information is missing, active follow-up should be 
undertaken. The subject must be followed-up until clinical recovery is complete and 
laboratory results have returned to normal, or until progression has been stabilized or until the 
last study visit, whichever comes first. This information should be documented in the 
subject’s medical records. 
9.3.3 AE Assessments 
9.3.3.1 Assessment of Severity 
Each AE will be assigned a category by the investigator as follows: 
Mild: 
An AE that is easily tolerated by the subject, causes minimal discomfort 
and does not interfere with everyday activities. 
Moderate: 
An AE that is sufficiently discomforting to interfere with normal 
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Severe: 
An AE that prevents normal everyday activities; treatment or other 
intervention usually needed. 
The most severe manifestation will be used for the final AE characterization. It will be 
recorded as the same AE. 
9.3.3.2 Assessment of Causality 
Every effort will be made by the investigator to assess the relationship of the AE, if any, to 
the IMD. Causality should be assessed using the categories presented in the following table: 
Unrelated: 
Clinical event with an incompatible time relationship to IMD use, and 
that could be explained by underlying disease or other drugs or 
chemicals or is incontrovertibly not related to the IMD. 
Unlikely: 
Clinical event whose time relationship to IMD use makes a causal 
connection improbable, but that could plausibly be explained by 
underlying disease or other drugs or chemicals. 
Possible: 
Clinical event with a reasonable time relationship to IMD use, but that 
could also be explained by concurrent disease or other drugs or 
chemicals. 
Probable: 
Clinical event with a reasonable time relationship to IMD use, and is 
unlikely to be attributed to concurrent disease or other drugs or 
chemicals. 
Very 
Likely/Certain: 
Clinical event with plausible time relationship to IMD use, and that 
cannot be explained by concurrent disease or other drugs or 
chemicals. 
 
9.3.3.3 Action Taken 
For each AE, the investigator will describe the action taken with the IMD in the appropriate 
section of the eCRF, as follows: 
 None 
 Medication or therapy provided 
 IMD removed 
 Concomitant medication changed 
 Other, specify. 
 
9.3.3.4 Outcome 
The outcome of an AE has to be classified as follows: unknown, recovered, not yet 
recovered, recovered with sequelae, death. 

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9.3.4 Pregnancy 
Pregnancy by itself will not be considered an AE. Hospitalization for a normal delivery or 
elective abortion of a normal fetus will not be considered as an SAE. However, the 
occurrence of an adverse pregnancy outcome for the mother or child may constitute an AE or 
SAE. If pregnancy occurs during the study, the investigator must inform the sponsor. 
9.3.5 Laboratory Assessments 
Screening for pregnancy will be performed (urine β-HCG at baseline [Day 0] visit only). 
9.3.6 Other Safety Assessments 
Wound infection incidence, diagnosed according to the CDC criteria for surgical site 
infection, will be assessed by an investigator at the Day 10, Month 1, Month 3/Early 
Discontinuation, and any unscheduled study visits. In addition, the infection will be assessed 
on a binary scale (“1 - yes” or “0 - no”) for the criteria below. A total score will be generated 
for each subject. 
 Presence of erythema 
 Presence of edema 
 Presence of pain at rest 
 Presence of elevated temperature 
9.4 
Data Safety Monitoring Board 
Not applicable. 
9.5 
Appropriateness of Measurements 
The efficacy and safety assessments planned for this study are widely used and generally 
recognized as reliable, accurate, and relevant to the disease condition. 
10 STATISTICAL METHODS 
10.1 Statistical and Analytical Plans 
A detailed statistical analysis plan (SAP) will be created and finalized before first subject first 
visit. Protocol deviations will be defined at the beginning of the study and data will be 
checked on a regular basis (ICH E6 [R2] addendum). 
A data review meeting will be convened to define the important protocol deviations. This will 
be held on clean data shortly before the database lock. 
10.1.1 Datasets or Populations Analyzed 
 The Enrolled Set includes all subjects who signed the informed consent form (ICF). 
 The Allocated Set includes all subjects who are allocated to treatment. 
 The Safety Analysis Set includes all subjects where the application of MAR-CUTIS 
or Dermabond Advanced has started. Subjects will be analyzed under the actual 
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 The Full Analysis Set (FAS) includes all subjects randomized that were allocated to 
one of the 2 treatment groups and had at least 1 posttreatment assessment. Subjects 
from the FAS will be analyzed under the randomized treatment group. 
 The Per Protocol Set (PPS) defines a subset of subjects in the FAS without any major 
protocol deviations affecting the primary endpoint. Subjects from the PPS will be 
analyzed under the randomized treatment group.   
10.1.2 Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized on the FAS population. 
10.1.3 Efficacy Variables 
Unless otherwise stated, efficacy analyses will be performed on the FAS population. 
10.1.3.1 Definition and Analysis of Primary Efficacy Endpoint 
10.1.3.1.1 Definition 
The primary efficacy endpoint will be the total dehiscence rate until the Day 10 visit. Thus, if 
the wound is assessed as showing dehiscence at Day 1 or an unscheduled visit before Day 10 
visit but showing “No” dehiscence at Day 10, dehiscence will be evaluated as “Yes” in the 
analysis. 
The dehiscence rate will be defined as “Yes” if the wound shows dehiscence, or “No” if the 
wound remains closed. 
10.1.3.1.2 Main Analysis 
During this trial, it is expected that a subject will have only one incision/laceration treated 
with the IMD (=target wound). In case the subject has more than one incision/laceration, the 
target wound will be the one with the greatest length (ie, the longest) that meets the study 
entry criteria. If the length of 2 or more wounds is equal, the investigator can choose either of 
them to be the target wound. Dehiscence will be assessed only for the target wound; for the 
analysis of the primary efficacy endpoint, only the treated target wound can and will be 
analyzed.  
To minimize any possible user bias in the dehiscence rates, sites will provide adequate 
training to all device users in cooperation with the sponsor. 
Missing data will be handled as described in Section 10.1.5. 
The primary null and alternative hypotheses to be tested in this trial is that treatment with 
MAR-CUTIS is noninferior to treatment with Dermabond at the margin of 8%, ie,  
H0: p_M – p_D ≥ 0.08  versus  H1: p_M – p_D < 0.08 
where p_M is the dehiscence rate of subjects treated with MAR-CUTIS, and p_D is the 
dehiscence rate of subjects treated with Dermabond. Since the dehiscence rates for both 
treatments are influenced by several factors, the effect of these will be considered and 
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Maximum-Likelihood estimates will be obtained fitting a logistic regression model to the 
dehiscence rates using the 3 randomization factors skin type (types I to III/types IV to VI), 
age group (2-21/≥22 years) and type of wound (incision/laceration), as well as treatment 
(MAR-CUTIS/Dermabond Advanced) as explanatory variables.  
The method of Farrington-Manning (FM; Farrington and Manning, 1990) will be applied to 
determine the variance estimator. 
Noninferiority will be declared if the upper limit of the 90% confidence interval (computed 
using the FM method) of the risk difference (computed from Maximum-Likelihood estimates 
after fitting a logistic regression) MAR-CUTIS:Dermabond is less than 8% in the FAS. 
If the logistic regression model as describe above does not converge due to a low number of 
subjects in one or more of the stratification factors, a back-up strategy for the analysis will be 
provided in the SAP. 
The following sensitivity analyses for primary efficacy will be performed: 
1) The primary efficacy analysis as described above will be repeated using the PPS. 
2) An analysis will be performed by repeating the logistic regression model described in 
the primary efficacy main analysis, albeit considering the length of the 
incision/laceration in the logistic regression model instead of the type of wound.  This 
analysis will be performed using the FAS.  
3) The primary efficacy analysis will be repeated, albeit by considering all subjects with 
missing data for the primary efficacy analysis as experiencing “Yes” dehiscence (ie, 
the wound did not remain closed). This analysis will be performed using the FAS.  
4) An additional sensitivity analysis will be performed using a Cochran-Mantel-
Haenszel (CMH; Cochran, 1954; Mantel and Haenszel, 1959) test. The dehiscence 
rates MAR-CUTIS:Dermabond will be analyzed with the CMH test, stratified by skin 
type (types I to III ; types IV to VI), age group (pediatric with age between 2 to 
21 years; adult with age ≥22 years), type of wound (incision; laceration) and treatment 
(MAR-CUTIS; Dermabond Advanced).  This analysis will be performed using the 
FAS. 
5) A final sensitivity analysis will be performed by repeating the logistic regression 
model described in the primary efficacy main analysis, albeit introducing additionally 
the effect of the center where the subject was treated (given by the center ID) in the 
logistic regression model.  This analysis will be performed using the FAS, and will 
only be considered if the logistic regression model converges.  
 
10.1.3.1.3 Supplementary Analyses 
Supplemental analyses may be performed and will be described in the SAP. 
10.1.3.2 Definition and Analysis of Secondary Efficacy Endpoints 
Secondary efficacy endpoints, as described in Section 6 are: 
 Comparison of the dehiscence rate between MAR-CUTIS and Dermabond Advanced 
at the Month 1 or Early Discontinuation visit. 

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 Score from POSAS recorded for the subject at Month 1 and Month 3/Early 
Discontinuation. 
 Comparison of wound infection incidence assessed on a binary scale (‘1-yes’ or ‘0-
no’) between both treatment groups. In addition, a total score will be calculated for 
each subject based on the wound infection assessed on the presence of erythema, 
edema, pain or elevated temperature (also assessed on a binary scale: “1-yes” or “0-
no” for each characteristic). 
 Score from POSAS recorded for the investigator at Month 1 and Month 3/Early 
Discontinuation. Assessments will be presented by subject treated. 
 Score from mHCS recorded for the investigator at Day 10 and Month 1 or Early 
Discontinuation. Assessments will be presented by subject treated. 
 Score from a questionnaire related to subject experience and satisfaction with the 
device at Day 10 and at Month 1 or Early Discontinuation. 
 Scores from 2 investigator-completed questionnaires to evaluate overall satisfaction 
and ease of use with the device: 
o A product-related questionnaire to be completed for each center when the 
last randomized subject at the center completes the Month 1 visit or at Early 
Discontinuation. This assessment will be presented by center. 
o A subject-related questionnaire at Day 0 and Month 1 or Early 
Discontinuation. This assessment will be presented by subject treated. 
Secondary efficacy endpoints will be summarized using descriptive statistics. 
FAS will be used on all analyses. 
10.1.3.3 Exploratory Analyses 
Exploratory analysis of dehiscence rates based on individual subgroups (eg, by wound type, 
skin type, or age group) might be performed. More details of these analyses will be provided 
in the SAP. 
10.1.4 Safety Variables 
Safety endpoints, as described in Section 6 are: 
 Adverse events classified by severity and relatedness to treatment. 
Descriptive analysis of safety variables will be performed on the Safety Analysis Set. In 
addition, descriptive analyses will be conducted within the randomization strata. Further 
information on each analysis will be provided in the SAP. 
 
10.1.5 Handling of Missing Data 
For the primary endpoint main analysis on the FAS population, any missing data for the 
primary endpoint will be handled as outlined in the following: 

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- 
Subjects with a provided reason for not attending the Day 10 Visit related to problems 
with the wound closure will be counted as a failure (ie, the subject experiences a 
dehiscence) 
- 
Subjects with a dehiscence experienced and recorded before the Day 10 Visit (Day 1 
or unscheduled visit) will be counted as a failure (ie, the subject experiences a 
dehiscence) 
- 
All other subjects (eg, lost to follow-up with no dehiscence before) will be counted as 
success (ie, the subject experiences no dehiscence up to Day 10 for the primary 
endpoint analysis), since it is expected that subjects with problems of wound closure 
will attend the Day 10 visit to see the investigator and assess the wound status, and 
given the very low expected rate of dehiscence 
In any case, all efforts will be made to contact subjects not attending Day 10 visit to gain 
information about the reason for nonattendance and about potential dehiscence. 
Further information on how to treat missing data for other variables will be given in the SAP. 

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10.2 Determination of Sample Size 
Assuming a dehiscence rate of 3.05% for MAR-CUTIS and 0.85% for Dermabond 
Advanced, 189 subjects (2:1, 126 MAR-CUTIS versus 63 Dermabond Advanced) ensure a 
power of 85% to show noninferiority of MAR-CUTIS compared with Dermabond Advanced 
using a one-sided significance level of α = 0.05 and a FM test given a noninferiority margin 
of 8%. 
The assumed dehiscence rates of 3.05% and 0.85% were derived based on the assumption to 
have 15% of subjects in the trial with lacerations that have a dehiscence rate of 0.5% for 
MAR-CUTIS and 0% for Dermabond Advanced and 85% of subjects in the trial with 
incisions, with dehiscence rates of  3.5% for MAR-CUTIS and 1% for Dermabond 
Advanced. 
Due to the lack of placebo information for ethical reasons, the assumed noninferiority margin 
of 8% is based on an average of dehiscence rates observed in previous studies, eg, Siddiqui 
DS et al 2013 (dehiscence between 2% to 13%), Muncie et al 2018 (dehiscence rates between 
0.8% to 7.5%), and Eymann et al 2010 (dehiscence rates between 2% and 24%). The 
KF7021-04 trial tries to mimic a real-life general surgery population. As such, a rather 
heterogeneous population is anticipated to be entered into the trial. Depending on the surgical 
indication, quite different dehiscence rates might be observed. Noninferiority versus a 
placebo would not be ethical in the context of this trial, and thus a non-inferiority design 
versus an approved IMD (Dermabond) has been set conservatively. The noninferiority 
margin is further supported by the fact that the use of no wound closure method would result 
in an expected dehiscence rate of 100%; the use of a placebo method (eg, adding a substance 
similar to a glue without any effect on wound closure) would be expected to be similar to no 
treatment, so that a noninferiority margin of 8% represents a clear improvement versus 
placebo. 
 
10.3 Protocol Deviations 
Deviations from the protocol will be defined in advance and documented on an ongoing basis 
during conduct of the clinical study. 
The investigator should not implement any deviation from, or changes of the protocol, 
without agreement by the sponsor and prior review and documented approval/favorable 
opinion from the Independent Ethics Committee or Institutional Review Board (IEC/IRB) of 
an amendment, except where necessary to eliminate an immediate hazard(s) to study subjects. 
The investigator, or person designated by the investigator, should document and explain any 
deviation from the approved protocol. 
Protocol deviations will be assessed individually on whether they are important or non-
important. A log will be maintained by Grünenthal of important protocol deviations. 
11 QUALITY ASSURANCE AND QUALITY CONTROL 
11.1 Audit and Inspection 
Study centers and study documentation may be subject to Quality Assurance audit during the 
course of the study by the sponsor or its nominated representative. In addition, inspections 
may be conducted by regulatory authorities at their discretion. 

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11.2 Monitoring 
Data for each subject will be recorded on an eCRF. Data collection must be completed for 
each subject/legal guardian who signs an ICF/assent form and is administered IMD. 
In accordance with current Good Clinical Practice (GCP) and ICH guidelines, the study 
monitor will carry out source document verification at regular intervals to ensure that the data 
collected in the eCRF are accurate and reliable. 
The investigator must permit the monitor, the IEC/IRB, the sponsor’s internal auditors, and 
representatives from regulatory authorities direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the eCRFs. 
11.3 Data Management and Coding 
Syneos Health will be responsible for activities associated with the data management of this 
study. This will include setting up a relevant database and data transfer mechanisms, along 
with appropriate validation of data and resolution of queries. Data generated within this 
clinical study will be handled according to the relevant standard operating procedures of the 
data management and biostatistics departments of Syneos Health. 
Study centers will enter data directly into an electronic data capture system by completing the 
eCRF via a secure internet connection. Data entered into the eCRF must be verifiable against 
source documents at the study center. Data to be recorded directly on the eCRF will be 
identified and the eCRF will be considered the source document. Any changes to the data 
entered into the electronic data capture system will be recorded in the audit trail and will be 
Food and Drug Administration CFR 21 Part 11 compliant. 
Medical coding will use the most recent version of the Medical Dictionary for Regulatory 
Activities for concomitant diseases and AEs, and WHODrug for medications. 
Missing or inconsistent data will be queried in writing to the investigator for clarification. 
Subsequent modifications to the database will be documented. 

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12 RECORDS AND SUPPLIES 
12.1 Investigational Medical Device Accountability 
Upon receipt of the IMD, the investigator (or deputy) will conduct an inventory of the 
supplies and verify that IMD supplies are received intact and in the correct amounts before 
completing a supplies receipt. The investigator will retain a copy of this receipt at the study 
center. The monitor may check the study supplies at each study center at any time during the 
study. 
It is the responsibility of the study monitor to ensure that the investigator (or deputy) has 
correctly documented the amount of the IMD received, dispensed, and returned on the 
dispensing log that will be provided. A full IMD accountability log will be maintained at the 
study center at all times. The study monitor will arrange collection of unused IMD returned 
by the subject. The study monitor will also perform an inventory of IMD at the close-out visit 
to the study center. All discrepancies must be accounted for and documented. 
12.2 Financing and Insurance 
Financing and insurance of this study will be outlined in a separate agreement between 
Syneos Health and the sponsor. 

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13 ETHICS 
13.1 Independent Ethics Committee or Institutional Review Board 
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the subjects, and any other relevant study documentation will be submitted 
to the appropriate IEC/IRB. Written approval of the study and all relevant study information 
must be obtained before the study center can be initiated or the IMD is released to the 
investigator. Any necessary extensions or renewals of IEC/IRB approval must be obtained for 
changes to the study such as amendments to the protocol, the ICF or other study 
documentation. The written approval of the IEC/IRB together with the approved ICF must be 
filed in the study files. 
The investigator will report promptly to the IEC/IRB any new information that may adversely 
affect the safety of the subjects or the conduct of the study. The investigator will submit 
written summaries of the study status to the IEC/IRB as required. On completion of the study, 
the IEC/IRB will be notified that the study has ended. 
13.2 Regulatory Authorities 
Relevant study documentation will be submitted to the regulatory authorities of the 
participating countries, according to local/national requirements, for review and approval 
before the beginning of the study. On completion of the study, the regulatory authorities will 
be notified that the study has ended. 
13.3 Ethical Conduct of the Study 
The investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, GCP, ICH 
guidelines, the applicable national and local laws and regulatory requirements, and 
International Standard ISO 14155:2011: Clinical investigation of medical devices for human 
subjects. 
13.4 Informed Consent 
The process of obtaining informed consent/assent must be in accordance with applicable 
regulatory requirement(s) and must adhere to GCP. 
The investigator is responsible for ensuring that no subject undergoes any study-related 
examination or activity before that subject/legal guardian has given written informed 
consent/assent to participate in the study. 
The investigator or designated personnel will inform the subject of the objectives, methods, 
anticipated benefits and potential risks and inconveniences of the study. The subject should 
be given every opportunity to ask for clarification of any points s/he does not understand and, 
if necessary, ask for more information. At the end of the interview, the subject will be given 
ample time to consider the study. Subjects will be required to sign and date the ICF. After 
signatures are obtained, the ICF will be kept and archived by the investigator in the 
investigator’s study file. A signed and dated copy of the subject ICF will be provided to the 
subject or their authorized representative. 

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It should be emphasized that the subject may refuse to enter the study or to withdraw from 
the study at any time, without consequences for their further care or penalty or loss of 
benefits to which the subject is otherwise entitled. Subjects/legal guardians who refuse to 
give or who withdraw written informed consent/assent should not be included or continue in 
the study. 
If new information becomes available that may be relevant to the subject’s willingness to 
continue participation in the study, a new ICF will be approved by the IEC(s)/IRB(s) (and 
regulatory authorities, if required). The study subjects will be informed about this new 
information and reconsent/reassent will be obtained. 
13.5 Subject Confidentiality 
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the 
IEC(s)/IRB(s) approving this research, as well as that of any other applicable agency(ies) 
such as the European Medicines Agency, will be granted direct access to the study subjects’ 
original medical records for verification of clinical study procedures and/or data, without 
violating the confidentiality of the subjects to the extent permitted by the law and regulations. 
In any presentations of the results of this study or in publications, the subjects’ identity will 
remain confidential. 
13.6 Reporting and Publication, Including Archiving 
Essential documents are those documents that individually and collectively permit evaluation 
of the study and quality of the data produced. After completion of the study (end of study 
defined as the date of the last visit of the last subject), all documents and data relating to the 
study will be kept in an orderly manner by the investigator in a secure study file. This file 
will be available for inspection by the sponsor or its representatives. Essential documents 
should be retained for 2 years after the final marketing approval in an ICH region or for at 
least 2 years since the discontinuation of clinical development of the investigational product. 
It is the responsibility of the sponsor to inform the study center when these documents no 
longer need to be retained. The investigator must contact the sponsor before destroying any 
study-related documentation. In addition, all subject medical records and other source 
documentation will be kept for the maximum time permitted by the hospital, institution, or 
medical practice. 
The sponsor must review and approve any results of the study or abstracts for professional 
meetings prepared by the investigator(s). Published data must not compromise the objectives 
of the study. Data from individual study centers in multi-center studies must not be published 
separately. 

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14 REFERENCES 
Bruns TB, Simon HK, McLario DJ, Sullivan KM, Wood RJ, Anand KJ. Laceration repair using a 
tissue adhesive in a children's emergency department. Pediatrics. 1996;98(4 Pt 1):673-5. 
Coover HW, Joyner FB, Shearer NH, Wicker TH. Chemistry and performance of cyanoacrylate 
adhesives. J Soc Plast Eng. 1959;15:413-7. 
Dumville JC, et al. Tissue adhesives for closure of surgical incisions. Cochrane Database Syst Rev. 
2014;(11):CD004287. 
Eymann R, Kiefer M. Glue instead of stitches: a minor change of the operative technique with a 
serious impact on the shunt infection rate. Acta Neurochirurgica Suppl. 2010;106:87-9. 
Farrington CP, Manning G. Test Statistics and Sample Size Formulae for Comparative Binomial 
Trials with Null Hypothesis of Non-zero Risk Difference or Non-unity Relative Risk. Stat Med. 
1990;9(12):1447-54. 
Farion K, et al. Tissue adhesives for traumatic lacerations in children and adults. Cochrane Database 
Syst Rev. 2002;(3):CD003326. 
Houston S, Hodge JW Jr, Ousterhout DK, Leonhard F. The effect of α‐cyanoacrylates on wound 
healing. J Biomed Mater Res 1969;3(2):281-9. 
Muncie C, Herman R, Collier A, Berch B, Blewett C, and Sawaya D. Wound complications after 
chemo-port placement in children: Does closure technique matter? J Pediatr Surg. 2018;53(3):572-5. 
Pocock SJ and Simon, R. Sequential treatment assignment with balancing for prognostic factors in the 
controlled clinical trial. Biometrics. 1975;31(1):103-15. 
Quinn J, et al. A randomized, controlled trial comparing a tissue adhesive with suturing in the repair 
of pediatric facial lacerations. Ann Emerg Med. 1993;22(7):1130-5. 
Quinn J, et al. A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the 
management of lacerations. JAMA. 1997;277(19):1527-30. 
Sajid MS, Siddiqui MR, Khan MA, Baig MK. Meta-analysis of skin adhesives versus sutures in 
closure of laparoscopic port-site wounds. Surg Endosc. 2009;23(6):1191-7. 
Siddiqui DS, Lacuna EM, Chen HY, and Chauhan SP. Skin closure of pfannenstiel incision with 
dermabond, staples, or suture during cesarean delivery: experience of a single attending. Am J 
Perinatol. 2013;30(3):219-24. 
Smith TO, Sexton D, Mann C, Donell S. Sutures versus staples for skin closure in orthopaedic 
surgery: meta-analysis. BMJ. 2010;340:c1199.  

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15 APPENDICES 
 
 

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15.1 Centers for Disease Control and Prevention Surgical Site Infection Criteria 
 

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15.2 Dermabond Advanced Instructions for Use 
 

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15.3 Patient and Observer Scar Assessment Scale 
 
 
 
 

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15.4 Modified Hollander Cosmesis Scale 
Modified Hollander Cosmesis Scale (part of the “Wound registry”) 
 
Evaluation Characteristics 
Yes (poor) 
No (good) 
Step-off borders 
1 
0 
Contour irregularities 
1 
0 
Wound margin separation 
1 
0 
Edge inversion 
1 
0 
Excessive inflammation 
1 
0 
Overall appearance 
1 
0 
 
 
 
 

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15.5 Product-related Questionnaire for Investigators 
Each investigator will complete this questionnaire after the assumed last 
randomized subject at the site has completed the Month 1 or Early 
Discontinuation (if earlier than Month 1) visit (one per site). 
 
Date of completion: dd/mmm/YYYY 
 
1) 
The instructions for use were: 
MAR-CUTIS 
Dermabond 
 
Clear and easy to understand 
for you 
Yes 
No 
Yes 
No 
 
Clear and easy to implement 
for subjects 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the issue below: 
 
 
if answered “No” for Dermabond, please explain the issue below: 
 
 
 
2) 
Package opening, assembly  
and preparation of the 
syringe was: 
MAR-CUTIS 
Dermabond 
 
Easy 
Yes 
No 
Yes 
No 
 
Fast 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the issue below: 
 
 
if answered “No” for Dermabond, please explain the issue below: 
 
 
 
3) 
Preparation of the target 
wound area was easy? 
MAR-CUTIS 
Dermabond 
 
 
Yes 
No 
Yes 
No 
 
 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the reason below: 
 
 
if answered “No” for Dermabond, please explain the reason below: 

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4) 
Appropriate thickness 
of the strip was easy to 
assess? 
MAR-CUTIS 
Dermabond 
 
 
Yes 
No 
Yes 
No 
 
 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the issue below: 
 
 
if answered “No” for Dermabond, please explain the issue below: 
 
 
 
5) 
Maintaining the target 
wound edges during 
application was easy: 
MAR-CUTIS 
Dermabond 
 
 
Yes 
No 
Yes 
No 
 
 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the issue below: 
 
 
if answered “No” for Dermabond, please explain the issue below: 
 
 
 
6) 
Precision of application 
was satisfactory? 
MAR-CUTIS 
Dermabond 
 
 
Yes 
No 
Yes 
No 
 
 
Yes 
No 
Yes 
No 
 
if answered “No” for MAR-CUTIS, please explain the reason below: 
 
 
if answered “No” for Dermabond, please explain the reason below: 
 
 
 
 
 

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7) 
Time for the glue to 
harden was: 
MAR-CUTIS 
Dermabond 
 
 
Too quick 
Too quick 
 
 
Too slow 
Too slow 
 
 
Just right 
Just right
 
If you have any comments, please provide below: 
 
 
8) 
Do you have previous 
experience with other 
topical skin adhesive? 
yes 
no 
 
If answered “yes”, 
 
 
Was MAR-CUTIS 
easier to apply than the 
other topical skin 
adhesives? 
yes 
no 
 
Was Dermabond easier 
to apply than the other 
topical skin adhesives? 
yes 
no 
 
 
9) 
Overall, the use of the 
glue made wound 
closure more hassle-
free for me than using 
sutures 
MAR-CUTIS 
Dermabond 
 
 
Yes 
No 
Yes 
No 
 
if answered “no” for MAR-CUTIS, please explain the reason below: 
 
 
if answered “no” for Dermabond, please explain the reason below: 
 
 
 
 
 
 
 
 

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Subject-related Questionnaire for investigators 
Please complete this questionnaire for each subject in the study at specified time points. 
 
Section 1 (to be completed at Day 0) 
1) Application of the glue strip 
Easy                                        Yes  No  
Fast                                        Yes  No  
Without complications                            Yes  No  
2) Overall, would you say that the use of the glue saved you time as compared with the use of 
sutures?                                        Yes  No 
3) Overall, would you say that the use of the glue reduced effort?      Yes  No 
 
Section 2 (to be completed at Month 1) 
Practical experience 
8) Please rate your impression on the usability of this product on a scale from 1 (poor = very 
difficult to use) to 100 (excellent = very easy to use) 
 
9) With regards to this subject, my experience with MAR-CUTIS can be described as 
 Very satisfied 
 Satisfied 
 Dissatisfied 
 Very dissatisfied 
10)Did you observe any pain or burning at time of application? 
 Yes 
 No 
 
Section 3 (to be completed only in case of intentional premature removal of the adhesive) 
1) Premature, intentional removal of glue strip was: 
Painless for subject                                   Yes  No 
Easy                                            Yes  No 
Quick                                           Yes  No 
Didn’t cause any additional complications                     Yes  No 
 if any answered “no”, please explain the issue below: 
 
 
Please explain which technique you used to remove the adhesive: 
 
 
Please provide reason(s) for the removal: 
 
 

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15.7 Subject-completed Questionnaire 
Questionnaire for Subjects 
Your opinion is very important to us and will help us to improve the quality of the product. We 
therefore would like to ask you to complete the following questionnaire which assesses positives 
and negatives of the wound closing method that has been used. Your doctor should be able to 
provide any help needed to complete this questionnaire. 
This questionnaire should take a few minutes to complete. 
Thank you 
___________________________________________________________________________ 
Section 1 (to be completed at Day 10 visit) 
1. Wound pain 
Please evaluate the pain you are now experiencing in the area of your wound by indicating on the 
100-mm line scale below with “no pain” at the left end (0 mm) and “excruciating pain” at the right” 
end (100 mm). 
 
My pain right now is: 
 
 
 
 
 
 
 
 
Please evaluate the average pain you have experienced in the area of your wound within the last 
seven (7) days by indicating on the 100-mm line scale below with “no pain” at the left end (0 mm) 
and “excruciating pain” at the right end (100 mm). 
 
 
 
 
 
 
 
 
 
No pain 
Excruciating pain 
0 
100 
No pain 
Excruciating pain 
0 
100 

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Section 2 (to be completed at Day 10 visit) 
2. Practical Experience/Ease of Use 
1)
You were given written instructions of how to take care of your wound after the 
surgery. Please answer the questions below by indicating ‘yes’ or ‘no’: 
The instructions were easy to understand     Yes  No  
The instructions were easy to implement     Yes  No  
 
2) How did the wound affect your daily activities? Please complete the table below, based 
on what you experienced after your surgical procedure: 
 
 
Very 
inconvenient 
A little bit 
inconvenient 
Neither 
positive, 
nor 
negative 
Convenient 
Very 
convenient 
Impact on your 
daily activities: 
During 
showering/washing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
When getting 
dressed and while 
wearing clothes  
 
 
 
 
 
 
 
 
 
 
During the day 
(moving, sitting, 
working) 
 
 
 
 
 
 
 
 
 
 
During the night 
(sleeping/lying in 
bed)  
 
 
 
 
 
 
 
 
 
 
 
3) How did you experience the application and changing of the wound dressing? 
I did it myself                     Yes  No  
Easy/no problem                   Yes  No  
4) The glue strip of MAR-CUTIS is transparent when applied to the skin. 
Did you find it useful?   Yes  No  Not applicable (had Dermabond)  
5) Please indicate how the wound closure felt on your skin: 
Comfortable                      Yes  No  
Tight (tension at the wound)            Yes  No  
Itchy                          Yes  No 
Loose (as if falling off)                Yes  No  
 
 
 

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1. Wound pain 
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2. Satisfaction/Preference 
 
2) My overall experience with the wound closure is best described as 
Very satisfied 
Satisfied 
Dissatisfied 
Very dissatisfied 
 
3) I would recommend this type of wound closure to a friend or relative   
 Yes  No 
 
 
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15.8 Contact Information for Safety Reporting 
The initial SAE notification report to be sent by e-mail or fax: 
e-mail 
 
 
Country 
Fax number 
France 
 
Germany 
 
Spain 
 
United Kingdom 
 
 
 
 

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15.9 Investigator Signature Page 
Protocol Title: 
A randomized, open-label, multi-center, controlled clinical study to 
compare MAR-CUTIS with Dermabond Advanced in closure of surgical 
incisions and lacerations ≤15cm 
Protocol Number: 
KF7021-04 
Confidentiality and Current Good Clinical Practice Compliance Statement 
I, the undersigned, have reviewed this protocol (and amendments), including appendices, and 
I will conduct the study as described in compliance with this protocol (and amendments), 
International Standard ISO 14155:2011: Clinical investigation of medical devices for human 
subjects, Good Clinical Practice, and Declaration of Helsinki. 
Once the protocol has been approved by the IEC/IRB, I will not modify this protocol without 
obtaining prior approval of Grünenthal GmbH and of the IEC/IRB. I will submit the protocol 
amendments and/or any ICF modifications to Grünenthal GmbH and IEC/IRB, and approval 
will be obtained before any amendments are implemented. 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential. No subjects’ names will be 
disclosed. All subjects will be identified by assigned numbers on all eCRFs, laboratory 
samples, or source documents forwarded to the sponsor. Clinical information may be 
reviewed by the sponsor or its agents or regulatory agencies. Agreement must be obtained 
from the subject before disclosure of subject information to a third party. 
Information developed in this clinical study may be disclosed by Grünenthal GmbH, to other 
clinical investigators, regulatory agencies, or other health authority or government agencies 
as required. 
Investigator Signature 
Date 
Printed Name 
Institution