Conditions: Pyoderma Gangrenosum
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 19
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether vilobelimab (development name: IFX-1) is safe and effective in the treatment of pyoderma gangrenosum.

Detailed description:
Neutrophilic dermatoses are a spectrum of inflammatory disorders characterized by skin lesions resulting from a neutrophil-rich inflammatory infiltrate in the absence of infection. Pyoderma gangrenosum is associated with a neutrophilic leukocytosis, which is likely to be triggered by C5a. This study is set up based on the hypothesis that vilobelimab might be able to block C5a induced pro-inflammatory effects such as neutrophil activation and cytokine generation, potentially contributing to the local skin inflammation and tissue damage.

Arms:
arm 1: Dose finding with a total of 15 doses of vilobelimab.

Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride.

All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8).

Starting at Day 15:

Group 1 (N=6) continued to receive vilobelimab 800 mg every 2 weeks (Q2W), with option to increase dose from Day 57 to 1600 mg every Q2W. arm 2: Dose finding with a total of 15 doses of vilobelimab.

Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride.

All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8).

Starting at Day 15:

Group 2 (N=6) received vilobelimab 1600 mg every 2 weeks (Q2W), with option to increase dose from Day 57 to 2400 mg every Q2W. arm 3: Dose finding with a total of 15 doses of vilobelimab.

Vilobelimab: IV infusions of vilobelimab diluted in sodium chloride.

All patients received vilobelimab 800 mg three times during the first week (Days 1, 4, and 8).

Starting at Day 15:

Group 3 (N=7) received vilobelimab 2400 mg every Q2W.

Interventions: intervention 1: vilobelimab
Intervention descriptions: intervention 1: IV infusions of vilobelimab diluted in sodium chloride.

Protocol document:
Prot_SAP_002.pdf: 
 
 
The information contained in this document is confidential and the proprietary property of 
InflaRx. Any unauthorized use or disclosure of such information without the prior written 
authorization of InflaRx is expressly prohibited. 
 
CLINICAL STUDY PROTOCOL 
 
OPEN LABEL EXPLORATORY PHASE IIA TRIAL TO INVESTIGATE THE 
SAFETY AND EFFICACY OF IFX-1 IN TREATING SUBJECTS WITH 
PYODERMA GANGRENOSUM (OPTIMA) 
Protocol Number: 
IFX-1-P2.7 
Compound: 
IFX-1 
Short Title: 
Exploratory study of IFX-1 in Pyoderma Gangrenosum 
Phase: 
II 
Indication: 
Treatment of pyoderma gangrenosum 
IND Number: 
136470 
Sponsor Name and 
Address: 
InflaRx 
Winzerlaer Strasse 2 
07745 Jena, Germany 
Version and Date: 
Version 4.0 Including Amendment 02, 14 May 2020 


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PROTOCOL SIGNATURES 
Confirmation of the Final Protocol 
We hereby certify that this is the final version of the protocol: 
Protocol Number: 
IFX-1-P2.7 including Amendment 01 
Title: 
Open label exploratory phase IIa trial to investigate the safety and 
efficacy of IFX-1 in treating subjects with Pyoderma Gangrenosum 
(OPTIMA). 
 
 
 
Sponsor Signatory: 
 
 
 
 
 
Program Director Dermatology 
InflaRx 
Winzerlaer Strasse 2 
07745 Jena, Germany 
telephone: 0049 89 414 189 7825 
 
Date 
 


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Statistician: 
 
 
 
 
 
Biostatistician 
Metronomia 
Clinical Research GmbH 
Paul-Gerhardt-Allee 42 
81245 München 
Germany 
 
Date 
 
 


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Signature of Coordinating Investigator: 
 
Protocol Number: 
IFX-1-P2.7 including Amendment 01 
Title: 
Open label exploratory phase IIa trial to investigate the safety and 
efficacy of IFX-1 in treating subjects with Pyoderma Gangrenosum. 
Herewith I declare that I have read and understood the present protocol and agree to honor 
each part of it. By signing this study protocol, I agree to conduct the clinical study, following 
approval by an Ethics Committee, in accordance with the study protocol, the current 
International Council for Harmonization Guidelines for Good Clinical Practice (GCP), and 
applicable regulatory requirements. I will ensure that all the subjects enrolled in the study by 
my site will be treated, observed, and documented in accordance with this protocol. I will 
ensure that all persons assisting with the study under my supervision are adequately informed 
about the protocol, the investigational product, and their duties. 
 
 
 
 
 
Coordinating Investigator 
Assistant Professor of Dermatology 
University of Toronto 
76 Grenville Street 
Toronto, Ontario 
M5S 1B2 
York Dermatology Center 
250 Harding Blvd. West, 
Suite 202,  
Richmond Hill, Ontario 
L4C 9M7,  
Canada 
 
Date 


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TABLE OF CONTENTS 
ABBREVIATIONS AND DEFINITIONS OF TERMS ......................................... 10 
1 SYNOPSIS OF STUDY .......................................................................................... 11 
2 SCHEDULE OF ASSESSMENTS ........................................................................ 19 
3 INTRODUCTION................................................................................................... 21 
3.1 Study Rationale ...................................................................................................... 21 
3.2 Background ............................................................................................................ 22 
3.2.1 IFX-1 ................................................................................................................... 22 
3.2.2 Pyoderma Gangrenosum ..................................................................................... 23 
3.2.3 Rationale for Dosing Regimen............................................................................ 25 
3.3 Benefit/Risk Assessment ....................................................................................... 26 
3.3.1 Expected Benefits ............................................................................................... 26 
3.3.2 Potential Risks .................................................................................................... 26 
3.3.3 Risk Associated with Lack of Efficacy ............................................................... 27 
3.3.4 Risk-Benefit Conclusion ..................................................................................... 27 
4 OBJECTIVES AND ENDPOINTS ....................................................................... 28 
5 STUDY DESIGN ..................................................................................................... 28 
5.1 Overall Design ....................................................................................................... 28 
5.2 Study Sites, Study Subject, and Expected Duration .............................................. 29 
5.3 End of Study Definition ......................................................................................... 29 
6 STUDY POPULATION ......................................................................................... 30 
6.1 Inclusion Criteria ................................................................................................... 30 
6.2 Exclusion Criteria .................................................................................................. 30 
6.3 Lifestyle Restrictions ............................................................................................. 30 
6.3.1 Meals and Dietary Restrictions ........................................................................... 30 
6.3.2 Caffeine, Alcohol, and Tobacco ......................................................................... 30 


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6.3.3 Activity ............................................................................................................... 30 
6.4 Screening Failures .................................................................................................. 30 
6.5 Gender distribution ................................................................................................ 31 
7 TREATMENT WITH IMP AND CONCOMITANT THERAPY ..................... 31 
7.1 Investigational Medicinal Product ......................................................................... 31 
7.1.1 Treatment Administered ..................................................................................... 31 
7.1.2 Dosing groups ..................................................................................................... 31 
7.1.3 Method of Treatment Assignment ...................................................................... 32 
7.1.4 Blinding............................................................................................................... 32 
7.1.5 Supply, storage and handling .............................................................................. 32 
7.1.6 Preparation and administration ........................................................................... 33 
7.1.7 Drug Accountability............................................................................................ 34 
7.1.8 Treatment Compliance ........................................................................................ 34 
7.1.9 Overdose of IMP ................................................................................................. 35 
7.2 Prior and Concomitant Therapy and Procedures ................................................... 35 
7.2.1 Recording of prior and concomitant therapy and procedures ............................. 35 
7.2.2 Allowed Concomitant Therapy ........................................................................... 36 
7.2.3 Prohibited Therapy.............................................................................................. 36 
7.3 Treatment After the End of the Study .................................................................... 37 
8 DISCONTINUATION/WITHDRAWAL CRITERIA ........................................ 37 
8.1 Discontinuation of the Study ................................................................................. 37 
8.2 Discontinuation of the IMP .................................................................................... 38 
8.3 Withdrawal from the Study .................................................................................... 38 
8.4 Lost to Follow-Up .................................................................................................. 39 
9 STUDY ASSESSMENTS AND PROCEDURES ................................................. 39 
9.1 Procedures at visits ................................................................................................ 39 


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9.1.1 Screening............................................................................................................. 40 
9.1.2 Start of IMP: Visit V1 (Day 1) ........................................................................... 41 
9.1.3 Treatment visits (Visits V2, V3, V5, V7, V8, V9, V11 to V15) ........................ 42 
9.1.3.1 Treatment visit V7 ........................................................................................... 43 
9.1.4 Treatment visits (Visits V4 and V6) ................................................................... 43 
9.1.5 Mid visit: Visit V10 ............................................................................................ 43 
9.1.6 End of treatment visit: Visit 16 (Day 189).......................................................... 44 
9.1.7 Observation visits................................................................................................ 45 
9.1.7.1 Visit Ob1 (End of treatment +30 days) ............................................................ 45 
9.1.7.2 Final Visit (End of Trial): Visit Ob2 (End of treatment +60 days) ................. 45 
9.1.8 Unscheduled visits .............................................................................................. 46 
9.2 Background characteristics .................................................................................... 47 
9.2.1 Demographics and Baseline Characteristics ....................................................... 47 
9.2.2 Medical History .................................................................................................. 47 
9.2.3 Concomitant medications.................................................................................... 47 
9.3 Efficacy Assessments............................................................................................. 47 
9.3.1 Wound Assessments ........................................................................................... 47 
9.3.2 Photographic documentation .............................................................................. 49 
9.3.3 Dermatology Life Quality Index ......................................................................... 49 
9.3.4 Numeric Rating Scale for Pain ........................................................................... 49 
9.4 Safety Assessments ................................................................................................ 50 
9.4.1 Safety Laboratory Assessments .......................................................................... 50 
9.4.2 Vital Signs ........................................................................................................... 51 
9.4.3 12-lead electrocardiograms ................................................................................. 51 
9.4.4 Physical Examination.......................................................................................... 52 
9.4.5 QuantiFERON-TB gold test ............................................................................... 52 


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9.4.6 Chest X-ray ......................................................................................................... 52 
9.4.7 Suicidal Risk Monitoring .................................................................................... 52 
9.4.8 Adverse Events ................................................................................................... 52 
9.4.8.1 Time Period and Frequency for Collecting adverse events and SAE 
Information ................................................................................................ 53 
9.4.8.2 Method of Detecting Adverse Events and SAEs ............................................. 53 
9.4.8.3 Follow-up of adverse events and SAEs ........................................................... 53 
9.4.8.4 Regulatory Reporting Requirements for SAEs ................................................ 53 
9.4.8.5 Pregnancy ......................................................................................................... 54 
9.4.9 Safety review ...................................................................................................... 54 
9.5 Immunostaining of biopsy ..................................................................................... 54 
9.6 IFX-1 concentrations ............................................................................................. 54 
9.7 Immunology and other assessments of blood, ulcer fluid, biopsy and stool samples
 .............................................................................................................. 55 
9.8 Genetic evaluations ................................................................................................ 56 
9.9 Health Economics .................................................................................................. 56 
9.10 Blood Sampling Volumes .................................................................................... 56 
10 STATISTICAL CONSIDERATIONS ................................................................ 57 
10.1 Sample Size Determination.................................................................................. 57 
10.2 Analysis Sets ........................................................................................................ 57 
10.3 Statistical Analyses .............................................................................................. 57 
10.3.1 Safety Analyses ................................................................................................. 57 
10.3.2 Efficacy Analyses ............................................................................................. 58 
10.3.3 Pain and Quality of Life Analyses .................................................................... 59 
10.3.4 Analyses of Concentrations of IFX-1 ............................................................... 59 
10.3.5 Other Analyses .................................................................................................. 60 
10.3.6 Interim Analyses ............................................................................................... 60 


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11 REFERENCES ...................................................................................................... 60 
12 APPENDICES ....................................................................................................... 64 
62 
Safety Laboratory Tests 
62 
63 
Regulatory and Ethical Considerations 
63 
69 
Adverse Events: Definitions and Procedures for Recording, 
Evaluation, Follow-up, and Reporting 
69 
77 
Contraceptive Guidance and Collections of Pregnancy Information 77 
81 
Prohibited biologics 
81 
82 
Permitted wound care 82 
83 
Amendment 01 
83 
103 
Amendment 02 
103 
 
LIST OF TABLES 
Table 1 Estimated Blood Sampling Volumes .......................................................................... 56 
Table 2 Protocol-Required Safety Laboratory Assessments ................................................... 65 
Table 3 Highly Effective Contraceptive Methods ................................................................... 80 
LIST OF FIGURES 
Figure 1 Study Design ............................................................................................................. 28 


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ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ANCOVA 
Analysis of covariance 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CRF 
Case report form 
ECG 
Electrocardiogram 
EOT 
End of treatment 
GCP 
Good clinical practice 
GDPR 
General Data Protection Regulation (European Union) 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed consent form 
IFN 
Interferon 
IL 
Interleukin 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
NRS 
Numeric rating scale 
Ob(x) 
Observation visit x 
PPS 
Per protocol set 
Q2W 
Every 2 weeks 
SAE 
Serious adverse event 
SAF 
Safety set 
SUSAR 
Suspected unexpected serious adverse reactions 
TEAE 
Treatment emergent adverse events 
TNF 
Tumor necrosis factor 
V(x) 
Visit x 
Definitions of Terms 
Term 
Definition 
Investigational medicinal 
product (IMP): 
A pharmaceutical form of an active substance or placebo being tested or used as 
a reference in a clinical study. 
Enrolled: 
A subject is considered to be enrolled in a study as soon as he/she signed 
informed consent (i.e., at screening). 
Measurement: 
Recording the value of a variable, e.g., recording of blood pressure. 
Procedure: 
Specific test performed on the subject, e.g., sphygmomanometry after 10 minutes 
in supine position. 
Assessment or 
evaluation: 
Systematic judgment of the recorded variable, e.g., clinical relevance of 
abnormal blood pressure. 
Variable: 
A measurable attribute or event that have either qualitative or quantitative values 
which may be expected to vary over time and within or between subjects, e.g.: 
diastolic blood pressure at baseline (mmHg); diastolic blood pressure at Week 4 
(mmHg) 
Endpoint: 
A variable that pertains to an objective of a study, e.g., mean change in diastolic 
blood pressure from baseline to Week 4 or percentage of responders at Week 4. 
Baseline value: 
The last measurement of a variable before the first dose of IMP. 
 
1 
SYNOPSIS OF STUDY 
Protocol Number: 
IFX-1-P2.7 
Protocol Title: 
Open label exploratory phase IIa trial to investigate the safety and efficacy of IFX-1 in 
treating subjects with Pyoderma Gangrenosum (OPTIMA). 
Short Title: 
Exploratory study of IFX-1 in Pyoderma Gangrenosum 
Phase: 
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Indication: 
Treatment of pyoderma gangrenosum 
IND Number: 
136470 
Study sites: 
Multiple 
Sponsor: 
InflaRx 
Winzerlaer Strasse 2 
07745 Jena, Germany 
Coordinating 
investigator: 
Afsaneh Alavi MD, Msc, FRCPC 
Assistant Professor of Dermatology 
York Dermatology Center 
250 Harding Blvd. West, 
Suite 312, 
Richmond Hill, 
Ontario, L4C 9M7, 
Canada 
Rationale: 
IFX-1 is a monoclonal antibody (which specifically binds to the soluble human complement 
split product C5a) that is being developed for the treatment of various diseases in which 
complement activation plays a role. 
Neutrophilic dermatoses are a spectrum of inflammatory disorders characterized by skin 
lesions resulting from a neutrophil-rich inflammatory infiltrate in the absence of infection. 
Pyoderma gangrenosum is associated with a neutrophilic leukocytosis, which is likely to be 
triggered by C5a. Pyoderma gangrenosum lesions have pronounced neutrophilic infiltration 
and the expression of interleukin (IL)-1β, IL-17, tumor necrosis factor (TNF)-alpha, and their 
receptors is significantly elevated, indicating an auto-inflammatory condition. C5a represents 
a promising target for blocking and modulating acute or chronic inflammation. Several 
animal models have demonstrated a positive impact of a blockade of the C5a/C5aR signaling 
axis on acute and chronic inflammatory diseases. A recent open label study deploying IFX-1 
in 12 subjects suffering from hidradenitis suppurativa revealed early evidence of disease 
modifying activity of IFX-1 in this neutrophil driven skin disorder, with a sustained clinical 
response even after only 8 weeks of treatment. Given the neutrophil driven nature of 
pyoderma gangrenosum, the current study is designed to investigate whether IFX-1 could 
also be a treatment option for this autoimmune type dermatosis. 




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Scientific exploratory parameters 
The following will be collected at the time points given in the Schedule of Assessments 
(Section 2). 
Blood for the analysis of: 
• 
 
 
 
 
 
 
 
 
 
 
 
Fluid draining from the target ulcer, if available, for the analysis of: 
• Immunology: 
◦ 
 
 
 
• Bacteria using a bacterial culture and polymerase chain reaction 
Biopsy from the target ulcer border tissue for immunostaining for: 
•
 
 
Stool samples for the analysis of: 
•
 
Absolute values and changes from the baseline value will be evaluated for the above 
parameters. 
In addition, routine safety laboratory tests will be performed. Blood will also be analyzed for 
antineutrophil cytoplasmic antibody (ANCA) and antinuclear antibody (ANA) formation. 
Overall Design: 
This is an open-label explorative study in subjects with pyoderma gangrenosum. Subjects 
will be examined according to the Schedule of Assessments (Section 2) at each visit. All 
subjects will receive IFX-1 (IMP). The IMP will be administered exclusively at site visits 
(Visit V1 to Visit V15). Examinations are defined in the Schedule of Assessments 
(Section 2). At the end of treatment with IMP, subjects should complete an End of Treatment 
(EOT; 
. Thereafter, subjects receive treatment for their pyoderma 


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gangrenosum at the discretion of the investigator. Subjects will be followed up for an 
additional
 after EOT for safety reason, with two observation visits (Visit Ob1 after 
30 days and Visit Ob 2 after 60 days). Visit Ob2 is the final visit in the study. 
Number of Subjects: 
This is planned to be a multi-center study with about 18 subjects treated with IMP (IFX-1). 
Subjects discontinuing treatment will not be replaced. It is expected that approximately 
15 subjects will undergo at least months treatment. 
Treatment Groups and Duration: 
The estimated recruitment period is approximately 6 to 12 months. 
The study duration for an individual subject includes screening (
), 
the treatment period (
), and the observational follow up 
). 
If a subject discontinues the trial prematurely for any reason, they should have a termination 
visit (Visit V16 = EOT) and should be followed up at Visit Ob1 and Visit Ob2. 
All subjects will receive IFX-1 at a maximum of 15 dosing visits. 
There will be 3 dosing groups (Group 1, Group 2, and Group 3) of 6 subjects each. Each 
group of subjects is recruited sequentially. The next dose group will be initiated if the 
previous dose was considered safe and well tolerated. If dosing in Group 2 cannot be 
initiated, then a further 6 patients will be recruited in Group 1. 
 


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Study Population Inclusion Criteria: 
Informed Consent 
1. Capable of giving signed informed consent as described in Regulatory and Ethical 
Considerations (63), which includes compliance with the requirements and 
restrictions listed in the informed consent form and in this protocol, and approval for 
photographic documentation 
Age 
2. Subjects must be18 years or older, at the time of signing the informed consent 
Sex 
3. Male or female 
Type of Subject and Disease Characteristics 
4. Diagnosis of an ulcerative form of pyoderma gangrenosum confirmed by the 
investigator 
5. In addition, the subject must fulfill at least 3 of the following 6 criteria at screening: 
 
History of 
• Pathergy (ulcer occurring at the sites of trauma) 
• Personal history of inflammatory bowel disease or inflammatory arthritis 
• History of papule, pustule or vesicle that rapidly ulcerated 
Clinical examination (or photographic evidence) of 
• 
Peripheral erythema, undermining border, and tenderness at site of 
ulceration 
• 
Multiple ulcerations 
• 
Cribriform or “wrinkled paper” scar(s) at sites of healed ulcers 
 
6. Subject has a minimum of 1 evaluable ulcer (≥2 cm2) at screening 
Study Population Exclusion Criteria: 
Subjects are excluded from the study if any of the following criteria apply: 
Related to Presenting Medical Condition 
1. Pyoderma gangrenosum target ulcer for more than 3 years before screening 
2. Surgical wound debridement within the previous 2 weeks before screening 
Other Medical Conditions 
3. Any comorbidity such as psychiatric or general illness that may put the subject at risk 
as determined by investigator 


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4. Poor general condition that might affect wound healing, as determined by the 
investigator 
5. One of the following abnormal laboratory findings at screening: 
• White blood cell count <3500/mm3 
• Platelet count <100,000/mm3 
• Hemoglobin <7 g/dL 
• Total bilirubin >1.5 times the upper limit of normal and/or alanine aminotransferase 
or aspartate aminotransferase >2.5 times upper limit of normal 
6. Human immunodeficiency virus, hepatitis B or hepatitis C viral screening test 
showing evidence of active or chronic viral infection at screening or a documented 
history of the human immunodeficiency virus, hepatitis B, or hepatitis C 
7. Evidence of active or latent tuberculosis 
8. History of malignancy in the previous 5 years (except for non-melanoma skin cancer 
and cancer in-situ of the cervix) 
9. Subjects with ulceration due to medical causes other than pyoderma gangrenosum  
(e.g. diabetic ulceration) 
Prior/Concomitant Therapy 
10. Infection requiring suppressive anti-infective therapy (such as latent tuberculosis, 
pneumocystis, aspergillosis, cytomegalovirus, herpes simplex virus, herpes zoster and 
atypical mycobacteria) 
11. Use of intravenous antibacterial, antiviral, anti-fungal, or anti-parasitic agents within 
30 days before screening 
12. Any drug treatment for pyoderma gangrenosum including corticosteroids (>10 mg 
prednisone or prednisone equivalent), intralesional steroids, cyclosporine A, 
biologicals and immunosuppressives (with the exception of antibiotics for wound 
superinfection) used within a time of 5 half-lives of the drug before screening (see 81) 
13. Received live attenuated vaccine within the previous 3 months before screening 
14. Major surgery planned during the time of foreseen study participation 
Prior/Concurrent Clinical Study Experience 
15. The subject has participated in an interventional clinical study during the 3 months 
before screening, or plans to participate in a clinical study 
16. Previous exposure to IFX-1 in this or another study 
17. Known hypersensitivity to polysorbate 80 (excipient of the IMP) 
Other Exclusion Criteria 
18. Prior exposure to anticomplement 5a before screening 
19. History of sever anaphylactic reaction to any components of C5a before screening 
20. Known or suspected active drug and/or alcohol abuse at screening 


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21. Breast feeding or pregnant woman at screening 
22. Male and female subjects of childbearing potential unwilling to follow the 
contraceptive guidance in 77 during the treatment period and for at least 30 days after 
the last dose of IMP 
23. Pregnancy or positive pregnancy test at screening 
24. The subject is imprisoned or lawfully kept in an institution at screening 
25. Evidence or suspicion that the subject might not comply with the requirements of the 
study protocol 
26. The subject is an employee or direct relative of an employee at the study site or 
sponsor 
27. Any other factor which, in the investigator’s opinion, is likely to compromise the 
subject’s ability to participate in the study 
Investigational medical product (IMP), dose, and mode of administration 
The IMP (IFX-1) will be provided in 
 glass vials at a concentration of  
 vial) for reconstitution and 
intravenous administration. For each dose, the required amount of IFX-1 will be diluted with 
 sodium chloride to a total volume of approximately 
mL and given to the subject as 
a single intravenous dose over 30 to 60 minutes during a site visit. 
All subjects will receive IFX-1 800 mg three times during the first week (Days 
). 
Starting at Day 
: 
• Subjects in Group 1 will continue to receive IFX-1 800 mg at 2 weekly intervals. 
• Subjects in Group 2 will receive IFX-1 1600 mg at 2 weekly intervals. 
• Subjects in Group 3 will receive IFX-1 2400 at 2 weekly intervals. 
At Day 
 (Visit V7), subjects in Groups 1 and 2 may have their dose increased to IFX-1 
1600 mg or 2400 mg, respectively, if there are no safety concerns and the Physician Global 
Assessment (main efficacy parameter) is ≥4. 
Subjects will receive a total of 
 doses of IFX-1. The first 3 doses will be given in the first 
week on Day , Day , and Day . The remaining doses will be given thereafter every 
2 weeks starting from Day 15. 
Statistical methods 
No sample size calculation has been performed for this explorative study. The sample size is 
based on practical considerations in this orphan disease. Interim analyses will be performed 
after each initial dosing group of 6 subjects has completed Visit V10. The interim analysis 
will comprise adverse events, Physician’s Global Assessment, and photographic 
documentation of area and volume. 


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The final analysis will be performed after all subjects have completed the trial including the 
EOT visit and the 2 observation visits, Visit Ob1 and Visit Ob2. 
To evaluate the primary objective of this study, TEAEs, related TEAEs and serious TEAEs 
will be analyzed according to the number and percentage of subjects who had an adverse 
event (of the respective category) as well as the number of adverse events by MedDRA 
System Organ Class and Preferred Term. Related TEAEs and serious TEAEs will be further 
grouped by severity and relationship. 
All other endpoints including efficacy, safety, pain and quality of life parameters will be 
analyzed descriptively by time point and change from baseline, as applicable. Continuous 
variables will be analyzed by absolute values and changes from baseline, if applicable. Basic 
descriptive statistics (e.g., number of observations (n), mean, standard deviation, minimum, 
median, maximum, lower quartile, upper quartile) will be displayed by visit or time point. 
The number and percentage of subjects in each category will be displayed by visit or time 
point for categorical or binary variables. 
Time to event endpoints which will be analyzed using Kaplan-Meier methods. 
Concentrations of IFX-1 will be summarized by time point. 
Statistical analyses will generally be performed for the entire study population as well as the 
3 dosing groups separately. Additional stratifications based on actual dosing and IMP 
compliance will be defined in the statistical analysis plan.




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DLQI = Dermatology Life Quality Index; NRS = numeric rating scale; Tx= Therapy; IMP = Investigational medicinal product; EOT = End of Treatment; ECG = 
Electrocardiogram. 
a Only if wound still open 
b An historical X ray may be used if taken within 6 months prior to screening 
c This photograph is the Baseline for subsequent Physician’s Global Assessments 
d Only for subjects in Group 1 and Group 2 


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3 
INTRODUCTION 
3.1 
Study Rationale 
Neutrophilic dermatoses are a spectrum of inflammatory disorders characterized by skin 
lesions resulting from a neutrophil-rich inflammatory infiltrate in the absence of infection. 
Neutrophil-rich cutaneous inflammation is also a cardinal feature of several auto-
inflammatory diseases with skin involvement, the latter being caused by aberrant innate 
immune responses. Over-activation of the innate immune system leading to increased 
production of IL-1 family members and ‘sterile’ neutrophil-rich cutaneous inflammation are 
features of both inherited auto-inflammatory syndromes with skin involvement and an 
increasing number of neutrophilic dermatoses. Therefore, auto-inflammation may be a cause 
of neutrophilic dermatoses (Satoh 2016). 
There are no data available on complement activation and C5a in patients with pyoderma 
gangrenosum. However, the disease is associated with a neutrophilic leukocytosis (Del 
Giacco 2011, Noblett 2009), which is likely to be triggered by C5a. 
Biopsies of pyoderma gangrenosum lesions also indicated pronounced neutrophilic 
infiltration (Tay 2014). In addition, in skin samples, the expression of IL-1β, IL-17, TNF-
alpha, and their receptors were significantly higher in pyoderma gangrenosum patients than 
in controls indicating that auto-inflammatory condition (Marzano 2017). 
IL-1b and its known target genes IL6, CXCL8, and IL36A were significantly increased in 
pyoderma gangrenosum skin lesions. Under IL1-beta therapy with canakinumab therapy, 4 of 
5 subjects showed a decrease in target-lesion size, Physician’s Global Assessment, and 
Dermatology Life Quality Index, and 3 of 5 achieved complete remission, supporting the 
auto-inflammatory hypothesis of the pathogenesis of pyoderma gangrenosum (Kolios 2015). 
The concept of blocking C5a-induced effects has been substantially reviewed in the literature 
and discussed as a potential new therapeutic approach in human dermatologic inflammatory 
diseases (Kanni 2018). 
C5a represents a promising target for blocking and modulating acute or chronic 
inflammation. Several animal models have demonstrated a positive impact on acute 
inflammation. Because increased plasma levels of C5a also occur during chronic 
inflammation, a positive effect may also be expected in chronic inflammatory diseases. 
Therefore IFX-1 could be a treatment option in the auto-inflammatory disease of pyoderma 
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3.2 
Background 
3.2.1 
IFX-1 
IFX-1 is a monoclonal antibody (which specifically binds to the soluble human complement 
split product C5a) that is being developed for the treatment of various diseases in which 
complement activation plays a role. 
Nonclinical studies have demonstrated that IFX-1 binds to its target rapidly and is capable of 
a nearly complete blockade of C5a-induced biological effects while not affecting cleavage of 
C5 and formation of the complement membrane attack complex. 
Single and repeated intravenous (iv) administration of IFX-1 at doses of up to 50 mg/kg over 
6 months in cynomolgus monkeys resulted in no related or relevant toxicological adverse 
findings within an extended core battery of safety pharmacology assessments. 
Various nonclinical studies have been conducted to assess pharmacological and toxicological 
aspects of IFX-1, none of which revealed any obvious toxicological or safety concerns for 
IFX-1. IFX-1 was well tolerated and did not show any toxicity with any of the doses tested. 
Therefore, the No Observed Adverse Effect Level was defined as the highest administered 
dose of 50 mg/kg (corresponding to a human equivalent dose of 16.13 mg/kg). 
IFX-1 is an IMP and is not approved in any country worldwide. To date, IFX-1 has been 
investigated in 1 Phase I study in healthy subjects and in 4 Phase II studies in subjects with 
early septic organ dysfunction, in subjects undergoing complex cardiac surgery, and in 
subjects with moderate to severe hidradenitis suppurativa: 
Study IFX-1-P1.1 (healthy subjects): in this Phase I study in 15 healthy subjects, 
5 consecutive dose groups (IFX-1 0.02, 0.1, 0.5, 2, and 4 mg/kg) received single iv infusions 
of IFX-1 or placebo. IFX-1 was safe and well tolerated. The following adverse events were 
reported by the investigator as at least possibly related to IFX-1: nausea, headache, 
nasopharyngitis, and C-reactive protein increased. 
Study IFX-1-P2.1 (subjects with early septic organ dysfunction): in this Phase II study in 
subjects with early septic organ dysfunction caused by pulmonary or abdominal infection, the 
safety, pharmacokinetics, pharmacodynamics, and efficacy of IFX-1 were investigated in 
3 different dose groups (IFX-1 2 × 2 mg/kg, 2 × 4 mg/kg, and 3 × 4 mg/kg, each with a 
placebo control). In total, 48 subjects were treated with IFX-1. IFX-1 was safe and well 
tolerated. The following adverse events were reported by the investigator as at least possibly 
related to IFX-1: acute hepatic failure, hepatocellular injury, pulmonary embolism, 
hypertension, atrial fibrillation, and impaired healing. 
Study IFX-1-P2.2 (subjects undergoing complex cardiac surgery): in this Phase II study in 
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pharmacodynamics, and safety of single doses of IFX-1 were investigated in 4 different dose 
groups (IFX-1 1, 2, 4, and 8 mg/kg, each with a placebo control). In total, 82 subjects were 
treated with IFX-1. IFX-1 was safe and well tolerated. The following adverse events were 
reported by the investigator as at least possibly related to IFX-1: leukocytosis, impaired 
healing, blood pressure decreased, and heart rate decreased. 
Study IFX-1-P2.3 (subjects with moderate to severe hidradenitis suppurativa): in this 
Phase II study in subjects with moderate to severe hidradenitis suppurativa, the safety, 
pharmacokinetics, pharmacodynamics, and efficacy of IFX-1 were investigated after 
9 weekly infusions of 800 mg. In total, 12 subjects were treated with IFX-1. IFX-1 was safe 
and well tolerated. There were no adverse events reported by the investigator as at least 
possibly related to IFX-1. 
Study IFX-1-P2.4 (subjects with moderate to severe hidradenitis suppurativa): in this 
Phase II study, 177 subjects were treated with either placebo or one of 4 different dose 
regimens of IFX-1 (400 or 800 mg every four weeks and 800 or 1200 mg every two weeks). 
The IFX-1 treatment was well tolerated and although most subjects experienced TEAEs, 
these were for the most part non-serious and similar in all treatment groups. IFX-1 treatment 
was associated with low immunogenicity. 
Further details on IFX-1 are given in the investigator’s brochure (the current version is 
available in the investigator site file). 
3.2.2 
Pyoderma Gangrenosum 
Pyoderma gangrenosum has an annual incidence of 3 to 10 per million (Cozzani 2014, 
Chatzinasiou 2016, Langan 2012) but the exact prevalence is difficult to determine due to 
missing data (Gameiro 2015). Any age may be affected, but it is most common in young and 
middle aged adults (Ahronowitz 2012, Wollina 2007, Chatzinasiou 2016, Gameiro 2015). 
This incidence is possibly higher in women (Chatzinasiou 2016, Langan 2012, Wollina 
2007). 
The diagnosis is based on clinical and histological findings; there is no pathognomonic 
clinical, histological, or biomarker finding. It is a diagnosis of exclusion, which even for 
experts is difficult. A diagnosis is supported by a rapid progression of a painful, necrolytic, 
cutaneous ulcer with an irregular, violaceous, and undermined border, with clinical findings 
(cribriform scarring), systemic diseases associated with pyoderma gangrenosum (e.g., 
ulcerative colitis), histopathologic findings (e.g., sterile dermal neutrophilic infiltration, 
mixed inflammation, lymphocytic vasculitis), and a history of pathergy (Sanchez 2004, Su 
2004). 
There are 4 disease types recognized: ulcerative (the classical variant, which is the focus of 
this trial), bullous (atypical), pustular, and vegetative (superficial, granulomatous). The 


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ulcerative variant is the most frequent, with lesions on the lower extremities and trunk. The 
purulent and painful lesions are small, rapidly expanding and ulcerating. 
Pyoderma gangrenosum may be associated with inflammatory bowel disease in up to 65% 
subjects, rheumatoid or poly-arthritis in 10 to 20% of subjects, and hematological disorders in 
up to 25% of subjects (DeFilippis 2015, Langan 2012, Vacas 2017). In about a quarter of 
subjects with pyoderma gangrenosum, it may have followed trauma (Cozzani 2014). Other 
disease associations are: pulmonary disease (Gade 2015), systemic lupus erythematosus 
(Gonzalez-Moreno 2015), viral and autoimmune hepatitis (Wat 2014, Pourmorteza 2016), 
Wilson’s disease (Freg 2016), primary immunodeficiency (common variable 
immunodeficiency; Simsek 2015: leucocyte adhesion deficiency; Thakur 2013, Madkaikar 
2015, Vahlquist 2015: chronic granulomatous disease; Nanoudis 2017), pregnancy (Steele 
2016, Takeshita 2017, Vigl 2016), and drugs (cocaine; Wang 2017: with less evidence for 
isoretinoin, propyluracil, sunitinib, levamisol; Wang 2017). 
There is substantial medical need for effective treatment for pyoderma gangrenosum. 
Subjects have severe pain, long times to complete healing, and frequent relapses. The risk of 
death is 3-times higher than controls (Langan 2012), with an inpatient death rate of 10-20% 
(Adisen 2016, Cabalag 2015, Ye 2014). However, as subjects with pyoderma gangrenosum 
usually have notable comorbidities, death may be due to these, an underlying associated 
disorder, or treatment. Response rates in subjects suitable for topical treatment has been 
reported to be only about 50%, but the response rates with biologicals has been reported to be 
between 20% and 90%. 
There is no “gold standard” for therapy (Gameiro 2015) or product license for use. Treatment 
comprises wound dressings, and medicinal treatments (e.g., corticosteroids, tacrolimus, 
sodium cromoglicate, nicotine, 5-aminosalicylic acid, cyclosporine, activated protein C, 
timolol gel) (Gameiro 2015, Reichrath 2005, Cabalag 2015, Cozzani 2014, Kim 2014, 
Moreira 2017). The treatment for more aggressive disease includes steroids, cyclosporine, 
azathioprine, sulfasalazine, dapsone, thalidomide, minocycline, clofazimine, methotrexate, 
mycophenolate mofetil, tacrolimus, intravenous immunoglobulin, cyclophosphamide, 
systemic antibiotics with anti-inflammatory activity (tetracyclines, vancomycin, rifampicin, 
and mezlocillin), and biologicals such as anakinra (anti-Il1 Receptor), especially with PAPA 
syndrome, anti-TNF alpha, especially with inflammatory bowel disease (etanercept reported 
not be effective), and ustekinumab (anti IL12, IL-23). 
The assessment of the response to therapy is hampered by the small number of study reports; 
most have been case reports or case series. 
3.2.3 
Rationale for Dosing Regimen 
In study IFX-1-P2.3, IFX-1 was administered in a dose of 800 mg per week for 8 weeks in 
subjects with hidradenitis suppurativa. As a result, a sustained hidradenitis suppurativa 
clinical response was observed. This started on Day 
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simulated patients were above the critical exposure if treated with 2400 mg IFX-1 every 
2 weeks. At this dose, only 0.3% and 0.1% of simulated patients were above the steady state 
AUC and Cmax NOAEL values, respectively. 
The time to ulcer healing in pyoderma gangrenosum varies in different trials of infliximab 
and other biologicals (Adişen et al. 2008, Foss et al. 2008, Brooklyn et al. 2006, Guenova et 
al. 2011, Kolios et al. 2015). However, an effect is likely to be seen after 6 to 8 weeks of 
treatment. The time to healing seems to correlate to ulcer size and is considered to be less 
than 2 months for ulcers smaller than 6 cm2. 
Therefore, this study will explore IFX-1 doses of 800 mg, 1600 mg, and 2400 mg given every 
2 weeks. All doses are covered by the NOAEL of 50 mg/mL. 
3.3 
Benefit/Risk Assessment 
IFX-1 has been investigated in a number of Phase II studies in which complement activation 
plays a role in the disease. Furthermore, considerations on risk-benefit-related aspects are 
derived from nonclinical data and clinical Phase I data in healthy subjects. 
3.3.1 
Expected Benefits 
The subjects participating in this study who are treated with IFX-1 may benefit from an 
improvement in symptoms and wound healing. 
3.3.2 
Potential Risks 
No obvious findings relevant to the safety of IFX-1 were detected during the extensive 
nonclinical in vitro/ex vivo and in vivo testing. In addition, IFX-1 has been demonstrated to 
be safe and well tolerated in healthy human subjects administered IFX-1 intravenously at 
single doses of up to 4 mg/kg. 
Furthermore, the safety of IFX-1 has been investigated in 3 Phase II studies. One study was 
conducted in 48 subjects with early septic organ dysfunction treated with up to 3 doses of 
4 mg/kg IFX-1 given over 4 days. A second study was conducted in 82 subjects undergoing 
complex cardiac surgery treated with single doses of up to 8 mg/kg IFX-1. The third study 
was conducted in 12 subjects with moderate to severe hidradenitis suppurativa treated with 
9 weekly infusions of 800 mg IFX-1. Overall, IFX-1 was safe and well tolerated in all these 
studies, and no additional risks associated with the administration of IFX-1 were observed. 
The potential risks associated with the intravenous administration of IFX-1 due to its mode of 
action include the following: 
Infections: A theoretical risk of infection exists due to the inhibition of C5a, therefore, 
investigators (and other health care professionals) should be vigilant for signs and symptoms 
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Meningitis/meningococcal septicemia: current data does not suggest that subjects treated with 
IFX-1 are at significantly increased risk of infection with N. meningitides and to date, no 
cases of meningitis or meningococcal septicemia have been reported in clinical studies with 
IFX-1. Therefore, mandatory vaccination or concomitant broad-spectrum antibiotic treatment 
is not warranted based on the mode of action for IFX-1. However, until a larger number of 
subjects have been exposed to IFX-1, investigators should be vigilant for signs of 
N. meningitides infection. 
Anaphylactic reactions and acute systemic allergic hypersensitivity: because IFX-1 is an 
antibody/protein, a general risk for anaphylactic reactions and acute systemic allergic 
hypersensitivity exists. Subjects who are included in this study are treated with IFX-1 at the 
study site so that adequate treatment and care is available in case of an anaphylactic reaction. 
To date, no anaphylactic reactions have been reported after administration of IFX-1 in 
clinical Phase I and Phase II studies. 
3.3.3 
Risk Associated with Lack of Efficacy 
No deterioration in health status is expected following the administration of IFX-1 in 
pyoderma gangrenosum. Nevertheless, deterioration can occur due to the fluctuating nature 
of the disease. In case of a lack of efficacy with IFX-1 treatment, subjects will continue to 
experience their typical symptoms. 
3.3.4 
Risk-Benefit Conclusion 
It is hypothesized that treatment with IFX-1 could block the C5a-mediated inflammatory 
effect and support wound healing. Thus, reducing the pain and consequent physical 
impairment associated with the lesions of pyoderma gangrenosum, and even improving the 
disease status. 
The hypothesized benefit of treatment with IFX-1, therefore, outweighs the potential risks for 
the subjects participating in this study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of IFX-1 may be found in the investigator’s brochure. 
4 
OBJECTIVES AND ENDPOINTS 
The objectives and endpoints are presented in the Synopsis (Objectives and Endpoints). 
5 
STUDY DESIGN 
5.1 
Overall Design 
Figure 1 
Study Design 
 
 


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Screening  
(Day -7 to  
-35) 
 
Treatment Period 
(Day 1 to Day 189) 
 
Observation Period (End 
of treatment +60 days) 
 
 
 
 
 
 
 
 
 
 
 
 
Initial dose 
(Day 1, 4, 8) 
 
Maintenance 
(Day 15 to 43) 
 
 
Uptitration 
(Day 57 to 169) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
800 mg Q2W 
(9 doses) 
 
 
Group 1 
(N = 6) 
 
800 mg 
(3 doses) 
 
800 mg Q2W 
(3 doses) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1600 mg Q2W 
(9 doses) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1600 mg Q2W 
(9 doses) 
 
 
Group 2 
(N = 6) 
 
800 mg 
(3 doses) 
 
1600 mg Q2W 
(3 doses) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2400 mg Q2W 
(9 doses) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group 3 
(N = 6) 
 
800 mg 
(3 doses) 
 
2400 mg Q2W 
(3 doses) 
 
 
2400 mg Q2W 
(9 doses) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: last day of dosing of IFX-1 is on Day 169 
Q2W = every 2 weeks 
This is an open-label explorative study. 
Subjects will be examined and receive IMP (IFX-1) according to the Schedule of 
Assessments (Section 2). IFX-1 will only be administered at a treatment visit. 
After completion of treatment with IMP (last IMP is given on Visit V15), subjects should 
complete an EOT visit at Day 
 (Visit V16). Subjects who discontinue early should, if 
possible, also complete the EOT visit. Thereafter, subjects should receive treatment for 
pyoderma gangrenosum at the discretion of the investigator. 
Subjects will be followed up for an additional 
days after EOT at Visit Ob1 (after 
 days) 
and Visit Ob2 (after 60 days) for safety reason. Visit Ob2 is the final visit in the study. 


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The allowed time windows for Visits V1 to V6 are ±2 days. All other visits have allowed 
time windows of ±5 days. There must be at least 48 hours between each dose of IFX-1 
(Section 34). Visits should be scheduled appropriately. 
5.2 
Study Sites, Study Subject, and Expected Duration 
This study is planned to be a multi-center study with about 18 subjects treated with IMP 
(IFX-1). 
The study start is defined as the date of the first visit of the first subject enrolled (signature of 
the informed consent form by the first subject), and the end of the study is defined as the date 
of the last visit of the last subject participating, as recorded in the Case Report Form (CRF). 
The estimated recruitment period is approximately 6 to 12 months. 
The study duration for an individual subject includes screening (14 days range 7 to 35 days), 
the treatment period (189 days ±5 days; the last day of dosing of IFX-1 is Day 169), and the 
observational follow up (60 days ±5 days). 
5.3 
End of Study Definition 
A subject is considered to have completed the study if all phases of the study have been 
completed including the last visit. 
The end of the study is defined as the date of the last visit of the last subject in the study. 
6 
STUDY POPULATION 
6.1 
Inclusion Criteria 
The inclusion criteria are presented in the synopsis (Study Population Inclusion Criteria). 
6.2 
Exclusion Criteria 
The exclusion criteria are presented in the synopsis (Study Population Exclusion Criteria). 
6.3 
Lifestyle Restrictions 
6.3.1 
Meals and Dietary Restrictions 
No restrictions pertaining to meals and dietary restrictions apply during the study. 
6.3.2 
Caffeine, Alcohol, and Tobacco 
No restrictions pertaining to caffeine, alcohol, or tobacco restrictions apply during the study. 






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The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all IMP received. Any discrepancies must be reported and 
resolved before use of the IMP. 
At each study site, authorized personnel will check the IMP for any loss, damage, or 
tampering and confirm receipt. Records of the receipt of IMP have to be maintained. 
Any technical complaints arising from defects in the quality of the IMP, or defects in the 
packaging or labeling of the IMP, must be reported to Almac or the sponsor at the earliest 
opportunity and the IMP should not be used. 
The authorized personnel at each site will be responsible for receipt adequate handling, 
storage, dispensing and preparation of the IMP, and local drug accountability as well as 
recording of the accurate administration of the IMP (i.e., complete administration of IMP, 
including flushing of the infusion line) used for each subject. 
The IMP must be stored at the site between 2°C and 8°C and should not be frozen. To record 
the temperature at the site, an established and validated local temperature management 
system with temperature logs should be used. If this is not possible, the responsible site 
personnel will maintain temperature records for the entire duration of the study. A template 
for the temperature records will be provided by the sponsor or sponsor’s designee. At a 
minimum, the daily (working day) minimum and maximum temperatures must be 
documented. 
Only subjects enrolled in the study may receive IMP and only authorized site staff may 
administer IMP. All IMP must be stored in a secure, temperature controlled, and monitored 
(manual or automated) area with access limited to the investigator and authorized site staff in 
accordance with the labeled storage conditions, separated from normal hospital inventories, 
and in compliance with applicable regulatory requirements. 
7.1.6 
Preparation and administration 
The IFX-1 for infusion will be reconstituted (prepared) under controlled conditions at the 
study site or at the study site’s pharmacy, in accordance with local regulations/requirements 
for aseptic reconstitution. 
The IMP will be diluted in sterile sodium chloride. The total volume in the infusion bag for 
each infusion should be approximately 
mL. 
The reconstituted IFX-1 should be used within 4 hours after dilution when stored at room 
temperature. Otherwise, the reconstituted IFX-1 has to be stored at 
 
) and used within 24 hours; if the reconstituted IFX-1 solution is stored in a fridge, it 
must be left to acclimatize to room temperature prior to administration. Details on 
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The number of unused, partially used, and empty vials will be documented accurately, and 
the vials will be kept at the site until the drug accountability documentation has been checked 
by the study monitor (Section 33). 
The IMP will be infused intravenously over a period of 30 to 60 minutes (± 10 min) via an 
intravenous line. Sites should use the supplied intravenous lines. The infusion may be briefly 
(<30 min) interrupted for technical reasons, or for reinsertion of the intravenous line. 
At the end of the infusion, the intravenous line will be briefly flushed with approximately 
10 mL of sterile sodium chloride to ensure that any IMP remaining in the intravenous line is 
administered. 
After each of the first 2 infusions of IMP administered, subjects must remain at the study site 
for at least 30 minutes after end of IMP administration; appropriate treatment for potential 
infusion-related reactions must be available during this time. 
Each administration of IMP will be recorded in detail in the source documentation and in the 
CRF. 
7.1.7 
Drug Accountability 
The investigator/institution is responsible for IMP accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
During the study, all IMP vials will be reconciled against the current inventory and the 
dispensing records as a component of the monitoring visits. 
IMP administration data kept at the site will be monitored throughout the study by the 
monitor. After completion of the study, copies of all records regarding the IMP will be 
provided to the sponsor, who will decide on the return or destruction of any unused IMP. 
If any unused IMP should be destroyed at the site (according to institutional policies, copies 
of which must be supplied to the sponsor or sponsor’s designee before destruction takes 
place, and in compliance with the current applicable regulatory requirements) after drug 
accountability has been assessed by the study monitor, this destruction must be documented. 
If unused IMP cannot be destroyed at the site, it needs to be returned to the depot. 
7.1.8 
Treatment Compliance 
If a subject misses a visit or a subject appears at the study center for a scheduled infusion but 
the infusion cannot be administered for any reason, the visit can be repeated within 3 days 
and the infusion given. Otherwise, the infusion will be considered as omitted and documented 
accordingly in the CRF. 


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Subjects who omit more than 2 scheduled (consecutive or non-consecutive) infusions will be 
discontinued from the study and will undergo the End of Treatment visit (Visit V16) and the 
2 observation visits. 
7.1.9 
Overdose of IMP 
At least 48 hours must have elapsed between each dose of IFX-1. Visits should be scheduled 
appropriately. Any second administration within this time, or any administration that is 
greater than the scheduled dose will be considered an overdose. The consequences of an 
overdose with IFX-1 are not known. InflaRx does not recommend specific treatment in case 
of an overdose. 
Overdoses must be recorded as TEAEs. 
In the event of an overdose, the investigator/treating physician should: 
1. Contact the sponsor or sponsor’s designee immediately. 
2. Closely monitor the subject for any adverse events or SAEs and laboratory abnormalities 
for at least 7 days. If more than 130% of the dose is given, the patient should be kept in 
hospital overnight. 
3. Obtain a plasma sample for IFX-1 concentrations if requested by the sponsor or 
sponsor’s designee (determined on a case-by-case basis). 
4. Document the quantity of the excess dose of the overdose in the CRF. 
5. If there are any symptoms, treatment should be initiated as deemed medically appropriate 
by the investigator. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the sponsor or sponsor’s designee based on the clinical evaluation of the 
subject. 
7.2 
Prior and Concomitant Therapy and Procedures 
7.2.1 
Recording of prior and concomitant therapy and procedures 
Any medication or vaccine (including procures such as laser- or photo-therapy, over-the-
counter or prescription medicines, vitamins, and/or herbal supplements) that the subject has 
used in the 3 months, or biologicals (see 81 for Prohibited Biologics) used within 12 months, 
before screening, is receiving at the time of screening, or receives during the study must be 
recorded in the source data and CRF along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose, frequency, and route of administration 


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The sponsor or sponsor’s designee should be contacted if there are any questions regarding 
concomitant or prior therapy. 
7.2.2 
Allowed Concomitant Therapy 
Wound care for pyoderma gangrenosum 
Wound care is performed at the scheduled visits, and 2 to 3 times a week depending on 
necessity according to the standard of care. 
Further details of wound care are given in 82. 
Concomitant use of wound care dressings on pyoderma gangrenosum ulcers is permitted with 
absorptive dressings, with or without antiseptics. However, the allowed antiseptics are limited 
(see 82). No topical therapy is allowed. Standard compression therapy throughout the study is 
required (Shavit and Alavi 2019). 
Antibiotic therapy for pyoderma gangrenosum 
Oral antibiotic therapy for treatment of superinfection of pyoderma gangrenosum wounds is 
permitted. 
Analgesic therapy for pyoderma gangrenosum 
Short-acting opioid or non-opioid analgesic therapy may be initiated at any time during the 
study. If possible, analgesic therapy should be avoided on the day of pain assessments until 
the assessments are made. 
Subjects will be required to report any analgesics that are taken. All use of analgesics and any 
dose adjustments will be recorded in the source documentation and in the CRF. 
7.2.3 
Prohibited Therapy 
The following therapies are prohibited for all subjects from screening until Visit EOT or 
discontinuation from the study: 
• Subject has received a live attenuated vaccine within 3 months prior to screening or 
plans to receive a live attenuated vaccine during the study or up to 4 weeks after the 
last study product administration. 
• New therapy with biologicals (see 81 for Prohibited Biologics). Biologicals used for 
an underlying disease at a stable dose may be continued 
• Any other systemic medication for pyoderma gangrenosum, including, but not limited 
to methotrexate, cyclosporine, retinoids, and fumaric acid esters 
• Oral or injectable corticosteroids (more than 10 mg prednisone or prednisone 
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• Non-stable, chronic use of high dose oral opioid analgesics 
• New prescription topical therapies for pyoderma gangrenosum 
• Over-the-counter topical antiseptic washes, creams, ointments, gels, and liquids 
containing antibacterial agents to treat pyoderma gangrenosum 
The following is prohibited for all subjects from screening until Visit Ob2 or discontinuation 
from the study: 
• Any investigational agent 
The investigator should contact the sponsor or sponsor’s designee if there are any questions 
regarding prior or concomitant therapy. 
7.3 
Treatment After the End of the Study 
No treatment with IFX-1 is foreseen after Visit EOT. The further treatment of the pyoderma 
gangrenosum is at the discretion of the investigator. 
8 
DISCONTINUATION/WITHDRAWAL CRITERIA 
Each early discontinuation of individual subject participation, irrespective of the reason for 
discontinuation, must be documented by the investigator. If possible, the date, circumstances, 
and reason for discontinuation should be documented. 
The investigator will attempt to complete all procedures usually required for Visit EOT for 
subjects discontinuing. See the Schedule of Assessments (Section 2) for data to be collected 
at the time of study discontinuation and follow-up and for any further evaluations that need to 
be completed. 
8.1 
Discontinuation of the Study 
The study may be discontinued by the sponsor at any site if any of the following criteria are 
met: 
• The study protocol is not adequately adhered to (protocol violations) despite training 
of the study site personnel 
• The data quality is deficient 
• The recruitment is inadequate 
Additionally, the entire study can be discontinued at all sites by the sponsor at any time for 
medical or ethical reasons. 
The investigator(s) will be notified in writing, outlining the reasons for discontinuation, and 
the investigator(s) must promptly inform all participating subjects. Detailed instructions on 
further assessments will be provided. 


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All study materials, except documents needed for archiving requirements, will be returned to 
the sponsor, including all records regarding the IMP, and the sponsor will decide on whether 
any unused IMP should be returned or destroyed. The sponsor or sponsor’s designee will 
ensure that any outstanding data clarification issues and queries are resolved and that all 
study records at the study site are complete. 
In accordance with applicable regulatory requirements, the sponsor or sponsor’s designee will 
promptly inform the competent regulatory authorities of the discontinuation and its reason(s), 
and the investigator or sponsor or sponsor’s designee will promptly inform the IRB. 
The approval of the study can be rescinded, or the study can be discontinued by a competent 
authority or a responsible IRB. 
8.2 
Discontinuation of the IMP 
Subjects must be discontinued from treatment with the IMP because of: 
• Unacceptable toxicity or TEAE, as determined by the investigator 
• Anaphylactic or other serious allergic reaction 
• Serious infection, including meningitis and sepsis 
• If, in the investigator’s opinion, continued administration of IMP could be detrimental 
to the subject’s well-being 
• Use of prohibited treatment that in the opinion of the investigator or sponsor or 
sponsor’s designee necessitates the subject being removed 
• Biopsy confirmation of any malignancy 
• Pregnancy 
• Abnormal liver function meeting Hy’s Law criteria (62). 
8.3 
Withdrawal from the Study 
A subject may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, compliance, 
or administrative reasons. 
Subjects may withdraw their consent at any time without giving reasons. Nevertheless, they 
should be asked about the reason(s) for discontinuation after being informed that they do not 
need to do so. Information as to when they withdrew consent must be documented. 
If the subject withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a subject withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the source data. 


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8.4 
Lost to Follow-Up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. The date of being lost to 
follow-up is defined as the last date with any assessment of the subject. 
The following actions must be taken if a subject fails to return to the study site for a required 
study visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 
• Before a subject is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the subject (e.g., 3 telephone calls at 3 different 
times on consecutive days or local equivalent methods). These contact attempts 
should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
9 
STUDY ASSESSMENTS AND PROCEDURES 
9.1 
Procedures at visits 
Study procedures and their timing are summarized in the Schedule of Assessments 
(Section 2). 
Immediate safety concerns should be discussed with the sponsor or sponsor’s designee 
promptly upon occurrence or awareness to determine if the subject should continue or 
discontinue IMP. 
Adherence to the study design requirements, including those specified in the Schedule of 
Assessments (Section 2), is essential and required for study conduct. 
9.1.1 
Screening 
Screening is the predetermined series of procedures with which each investigator selects an 
appropriate and representative sample of subjects for enrollment into the study. 
The screening procedures will be conducted within 
) before first 
administration of IMP. 
The investigator will maintain a screening log to record details of all subjects screened and to 
confirm eligibility or record reasons for screening failure, as applicable. Subjects who fail 
screening may be re-screened once at a later date. 


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All screening evaluations must be completed and reviewed to confirm that potential subjects 
meet all eligibility criteria. The data for the inclusion and exclusion criteria must be reported 
in the source data and CRF. 
The investigator may pre-screen subjects for study inclusion and exclusion criteria without 
first obtaining written informed consent for participation in the current study on the basis of 
either of the following situations: 
• Pre-existing data (e.g., for study inclusion and exclusion criteria, as available in 
medical records held by the investigator) 
• Initial contact (e.g., routine visit, phone call) where only routine and/or non-study 
specific questions are allowed 
Procedures conducted as part of the subject’s routine clinical management (e.g., blood count) 
and obtained before signing of the informed consent form may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the Schedule of Assessments (Section 2). 
After subjects have provided written informed consent, they will be assessed at the screening 
visit to determine if all inclusion criteria and no exclusion criteria are met. All subjects must 
provide written informed consent before any study-specific assessments or procedures are 
performed. 
The following procedures will be conducted and documented at the Screening visit: 
• Initiate and complete informed consent procedure and document process 
• Record demographic and baseline characteristics 
• Record relevant medical and surgical history during the 6 months before Screening 
• Initiate documentation of concomitant medications 
• Assess target ulcer (degree of erythema and border elevation) 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Perform a physical examination 
• Record body weight 
• Record vital signs 
• Record a 12 lead ECG 
• Perform a chest X-ray. An historical X-ray can be used if taken within 6 months prior 
to screening 
• Take photograph of target ulcer for area and volume measurements 
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◦ 
Safety laboratory parameters (clinical chemistry and hematology) 
◦ 
Human immunodeficiency virus, hepatitis B virus, and hepatitis C virus test 
◦ 
Pregnancy test for women of childbearing potential 
◦ 
QuantiFERON-TB gold test for the presence of tuberculosis 
• Take urine for urinalysis 
• Use a standard dressing and compression therapy for the target ulcer 
• Record Adverse Events 
9.1.2 
Start of IMP: Visit V1 (Day 1) 
The following will be performed at Visit V1: 
• Review all inclusion and exclusion criteria 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Document concomitant medications 
• Record adverse events 
• Record body weight 
• Record vital signs 
• Perform a physical examination 
• Assess target ulcer (degree of erythema and border elevation) 
• Take photograph of target ulcer for area and volume measurements. This photograph 
is the baseline for the recording of the Physician’s Global Assessment at subsequent 
visits. 
• Record a 12 lead ECG 
• Take blood for 
◦ 
Immunology 
◦ 
Anti-drug antibody, antineutrophil cytoplasmic antibody, and antinuclear antibody 
• Take a sample of the target ulcer fluid if wound is open and liquid is available 
• Take a biopsy of the target ulcer 
• Perform a urine pregnancy test for a woman of childbearing potential 
• Take a stool sample for the measurement of calprotectin 
• Use a standard dressing and compression therapy for the target ulcer 
If the subject fulfills all of the inclusion criteria, does not meet any of the exclusion criteria, 
and written informed consent is available, the subject will be started on IMP. 


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• Assign subject to treatment 
• Administer IMP 
• Update recording of adverse events 
Subjects enrolled into the study will be issued a subject card with relevant contact details, 
including emergency contact details. 
If the subject meets an exclusion criterion or another reason for non-inclusion in the study is 
present after obtaining informed consent, the subject will not be enrolled into the study and 
will be deemed as screen failure. 
9.1.3 
Treatment visits (Visits V2, V3, V5, V7, V8, V9, V11 to V15) 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Document concomitant medications 
• Record adverse events 
• Record vital signs 
• Record the Physician’s Global Assessment 
• Assess target ulcer (degree of erythema and border elevation) 
• Take photograph of target ulcer for area and volume measurements 
• Use a standard dressing and compression therapy for the target ulcer 
• Preform urine pregnancy test for a woman of childbearing potential (Visits V8, V12, 
and V14) 
• Administer IMP 
• Update recording of adverse events 
9.1.3.1 
Treatment visit V7 
In addition to the assessments and procedures outlined in the Schedule of Assessments 
(Section 19), the dose of IFX-1 will be assessed and increased in subjects of Group 1 and 
Group 2 if the dose escalation criteria are met (Section 31). 
9.1.4 
Treatment visits (Visits V4 and V6) 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Document concomitant medications 


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• Record adverse events 
• Record vital signs 
• Record the Physician’s Global Assessment 
• Take photograph of target ulcer for area and volume measurements 
• Assess target ulcer (degree of erythema and border elevation) 
• Take a sample of the target ulcer fluid if wound is open and liquid is available 
• Use a standard dressing and compression therapy for the target ulcer 
• Take blood for 
◦ 
Safety laboratory parameters (clinical chemistry and hematology) 
◦ 
IFX-1 concentrations 
◦ 
Immunology 
◦ 
Anti-drug antibody 
• Take a urine sample for urinalysis 
• Perform a urine pregnancy test for a woman of childbearing potential 
• Take a stool sample for the measurement of calprotectin 
• Administer IMP 
• Update recording of adverse events 
9.1.5 
Mid visit: Visit V10 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Document concomitant medications 
• Record adverse events 
• Perform a physical Examination 
• Record vital signs 
• Record body weight 
• Record the Physician’s Global Assessment 
• Take photograph of target ulcer for area and volume measurements 
• Assess target ulcer (degree of erythema and border elevation) 
• Take a sample of the target ulcer fluid if wound is open and liquid is available 
• Use a standard dressing and compression therapy for the target ulcer 


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• Take blood for 
◦ 
Safety laboratory parameters (clinical chemistry and hematology) 
◦ 
Pregnancy test for a woman of childbearing potential 
◦ 
IFX-1 concentrations 
◦ 
Immunology 
◦ 
Anti-drug antibody 
• Take a urine sample for urinalysis 
• Take a stool sample for the measurement of calprotectin 
• Administer IMP 
• Update recording of adverse events 
9.1.6 
End of treatment visit: Visit 16 (Day 189) 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Document concomitant medications 
• Perform a physical Examination 
• Record vital signs 
• Record body weight 
• Record 12 lead ECG 
• Record the Physician’s Global Assessment 
• Take photograph of target ulcer for area and volume measurements 
• Assess target ulcer (degree of erythema and border elevation) 
• Take a sample of the target ulcer fluid if wound is open and liquid is available 
• Use a standard dressing and compression therapy for the target ulcer 
• Take blood for 
◦ 
Safety laboratory parameters (clinical chemistry and hematology) 
◦ 
Pregnancy test for a woman of childbearing potential 
◦ 
IFX-1 concentrations 
◦ 
Immunology 
◦ 
Anti-drug antibody 
• Take a urine sample for urinalysis 


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• Take a stool sample for the measurement of calprotectin 
• Record adverse events 
9.1.7 
Observation visits 
9.1.7.1 
Visit Ob1 (End of treatment +30 days) 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Document concomitant medications 
• Record vital signs 
• Record the Physician’s Global Assessment 
• Take photograph of target ulcer for area and volume measurements 
• Assess target ulcer (degree of erythema and border elevation) 
• Take blood for 
◦ 
IFX-1 concentrations 
◦ 
Immunology 
◦ 
Anti-drug antibody 
• Record adverse events 
9.1.7.2 
Final Visit (End of Trial): Visit Ob2 (End of treatment +60 days) 
The following assessments and procedures will be performed as outlined in the Schedule of 
Assessments (Section 19): 
• Record Dermatology Life Quality Index 
• Record pain intensity using a numeric rating scale 
• Document concomitant medications 
• Perform a physical Examination 
• Record vital signs 
• Record body weight 
• Record the Physician’s Global Assessment 
• Take photograph of target ulcer for area and volume measurements 
• Assess target ulcer (degree of erythema and border elevation) 
• Take blood for 
◦ 
Safety laboratory parameters (clinical chemistry and hematology) 
◦ 
Pregnancy test for a woman of childbearing potential 


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◦ 
IFX-1 concentrations 
◦ 
Immunology 
◦ 
Anti-drug antibody 
• Take a urine sample for urinalysis 
• Record adverse events 
9.1.8 
Unscheduled visits 
Unscheduled visits to the study site will be arranged as needed for subjects who require 
additional follow-up assessments (e.g., due to an SAE, abnormal laboratory safety findings, 
loss of response). 
At a minimum, the following assessments and procedures will be performed at each 
unscheduled visit: 
• 
Vital signs 
• 
Documentation of adverse events 
• 
Documentation of concomitant therapy 
 
9.2 
Background characteristics 
9.2.1 
Demographics and Baseline Characteristics 
The following demographic data and baseline characteristics will be documented at 
screening: 
• Age 
• Gender 
• Race and ethnicity 
• Body weight (For weight measurements, the subject is allowed to wear light indoor, 
daytime clothing with no shoes.) 
• Height 
9.2.2 
Medical History 
Relevant medical (and surgical history), including date of diagnosis of pyoderma 
gangrenosum, in the investigator’s opinion will be recorded in the CRF at screening. The 
medical history will be reviewed and updated on Day 1 to ensure that the subject remains 
qualified for the study. 


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9.2.3 
Concomitant medications 
All prior and concomitant therapy will be documented, as described in Section 34. 
9.3 
Efficacy Assessments 
Efficacy will be assessed on the basis of the following variables: 
• Wound assessment (Physician’s Global Assessment, erythema, border elevation) 
• Photographic documentation 
• Dermatology Life Quality Index 
• Numeric Rating Scale for pain 
9.3.1 
Wound Assessments 
The investigator will score the degree of wound healing, erythema, border elevation and the 
presence of remission 
Physician’s Global Assessment 
The following scores will be used to rate overall efficacy (Foss 2008): 
Severity score Description 
0 
Completely clear: except for possible residual hyperpigmentation 
1 
Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky 
erythema and/or very small ulceration 
2 
Marked improvement: significant improvement (about 75%); however, a small amount of 
disease remaining (i.e. remaining ulcers, although have decreased in size, minimal erythema 
and/or barely perceptible border elevation) 
3 
Moderate improvement: intermediate between slight and marked; representing about 50% 
improvement 
4 
Slight improvement: some improvement (about 25%); however, significant disease remaining 
(i.e. remaining ulcers with only minor decrease in size, erythema or border elevation) 
5 
No change from baseline 
6 
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Wound erythema 
Wound erythema will be assessed as follows (Foss 2008): 
Severity rating (score) Description 
None (0) 
No erythema 
Slight (1) 
Mild pink color 
Moderate (2) 
Moderate pink color 
Severe (3) 
Reddish color 
Very severe (4) 
Dark red or violaceous 
Border elevation 
Border elevation will be assessed as follows (Foss 2008): 
Severity rating (score) Description 
None (0) 
Border is flat with ulcer and surrounding skin, no elevation 
Slight (1) 
Slight elevation of border above ulceration and surrounding skin 
Moderate (2) 
Noticeable elevation of border above ulceration and surrounding skin 
Severe (3) 
Significant elevation of border above ulceration and surrounding skin 
Very severe (4) 
Border rolled high above ulceration and surrounding skin 
9.3.2 
Photographic documentation 
Photographs taken of the affected wound areas will be taken during the study at the times 
specified in the Schedule of Assessments (Section 19). The photographic documentation will 
be used to estimate the area and volume of the wound. 
9.3.3 
Dermatology Life Quality Index 
The Dermatology Life Quality Index is an established and widely used patient-reported 
outcome instrument for assessing the impact on health-related quality of life due to 
dermatological conditions in clinical studies. The questionnaire will be completed by the 
subject. 
A score is documented for each of the 10 items, ranging from 0 to 3 for each item. Items 
include, for example: 
• Over the last week, how itchy, sore, painful, or stinging has your skin been? 
• Over the last week, has your skin prevented you from working or studying? 
• Over the last week, how much of a problem has the treatment for your skin been, for 
example by making your home messy, or by taking up time? 


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The total score is the sum of the responses to all 10 items, ranging from 0 to 30. A higher 
score corresponds to worse Health-related quality of life. Guidelines with regard to the 
scoring of each question and the handling of incorrectly completed questionnaires are taken 
from the Dermatology Life Quality Index manual 
(http://sites.cardiff.ac.uk/dermatology/quality-of-life/dermatology-quality-of-life-index-
dlqi/dlqi-instructions-for-use-and-scoring/). 
To avoid biasing the subject’s response, the subject should complete the questionnaire at the 
study site before any other assessments and before any interaction with the study site 
personnel has occurred. 
9.3.4 
Numeric Rating Scale for Pain 
The numerical rating scale (NRS) is perhaps the most common pain assessment tool used. It 
is an 11-point scale (from 0 represent no pain to 10 representing the worst pain the subject 
can imagine). Subjects are asked to rate the intensity of their pain “right now” verbally with a 
number. The value is recorded in the CRF. The validity of the NRS has been well established 
and it has been shown to be easy to use. 
9.4 
Safety Assessments 
Planned time points for all safety assessments are provided in the Schedule of Assessments 
(Section 2). 
The following safety variables will be collected: 
• Safety laboratory parameters 
• Vital signs 
• 12-lead electrocardiogram (ECG) 
• Physical examination 
• QuantiFERON-TB Gold test 
• Adverse events 
• Pregnancy test 
• Chest X-ray 
9.4.1 
Safety Laboratory Assessments 
See 62 for the list of safety laboratory tests to be performed and the Schedule of Assessments 
(Section 2) for the timing and frequency of the tests. 
The safety laboratory assessments will be performed by a central laboratory. 
Urinalysis will be centrally performed using a dipstick. 


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The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the adverse event section of the 
CRF. The laboratory reports must be filed with the source documents. 
All abnormal laboratory values will require a comment in the CRF according to the following 
classification: 
• NCS = not clinically significant 
• CS = clinically significant 
• Error (e.g., laboratory error, improper sample preparation, hemolysis, or delayed 
transit to laboratory) 
Clinically significant abnormal laboratory findings are those which are not associated with 
the underlying disease, unless judged by the investigator to be more severe than expected for 
the subject’s condition. 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within 30 days after the last dose of IMP should be repeated until 
the values return to normal or baseline, or are no longer considered clinically significant by 
the investigator or sponsor. 
If such values do not return to normal/baseline within a period of time judged reasonable by 
the investigator, the etiology should be identified, and the sponsor or sponsor’s designee 
notified. 
All protocol-required laboratory assessments, as defined in 62, must be conducted in 
accordance with the laboratory manual and the Schedule of Assessments (Section 2). 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in subject management or are considered 
clinically significant by the investigator (e.g., SAE or adverse event or stopping IMP), then 
the results must be recorded in the CRF. 
9.4.2 
Vital Signs 
Vital signs will be measured in a semi-supine position after 5 minutes of rest and will include 
temperature, systolic and diastolic blood pressure, pulse and respiratory rate. Blood pressure 
and pulse measurements will be assessed with a completely automated device. Manual 
techniques will be used only if the automated device is not available and will be measured in 
the following way: Three readings of blood pressure and pulse will be taken. The first reading 
should be rejected. The second and third readings should be averaged to give the 
measurement to be recorded in the CRF. 


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9.4.3 
12-lead electrocardiograms 
12-lead ECG data will be collected for screening and routine safety monitoring. 
A single 12-lead ECG will be obtained as outlined in the Schedule of Assessments 
(Section 2) using an ECG machine that automatically calculates the heart rate and measures 
PR, QRS, QT, and QTc (Bazett) intervals. 
Subjects can have a repeat ECG examination at any time during the study if considered 
necessary by the investigator. 
The investigator will interpret each ECG. Any clinically significant and non-clinically 
significant findings will be recorded in the source documentation. The ECGs will be assessed 
to decide if changes from baseline represent an adverse event. 
9.4.4 
Physical Examination 
A complete physical examination will include, at a minimum, assessments of the 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
An abnormality noted after starting treatment with IMP (Visit V1) will be evaluated by the 
investigator for whether it constitutes an adverse event. 
9.4.5 
QuantiFERON-TB gold test 
The QuantiFERON-TB Gold is a simple blood test that aids in the detection of 
Mycobacterium tuberculosis. It is an IFN-gamma release assay and is unaffected by previous 
Bacille Calmette-Guerin (BCG) vaccination. It cannot distinguish between active tuberculosis 
disease and latent tuberculosis infection. 
9.4.6 
Chest X-ray 
A standard chest X-ray will be performed at screening to exclude tuberculosis. An historical 
X-ray can be used if taken within 6 months prior to screening. 
9.4.7 
Suicidal Risk Monitoring 
No suicidal risk monitoring will be performed as IFX-1 is not centrally active. 
9.4.8 
Adverse Events 
The definitions of an adverse event, adverse event of special interest, and SAE can be found 
in 69. 


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Adverse events will be reported by the subject (or, when appropriate, by a caregiver, 
surrogate, or the subject’s legally authorized representative). 
The investigator and any designees are responsible for detecting, documenting, recording, 
and reporting (to the sponsor) adverse events, adverse events of special interest, or SAEs. 
They are also responsible for following up all adverse events until their resolution or until a 
steady state of the event is reached. 
9.4.8.1 
Time Period and Frequency for Collecting adverse events and SAE 
Information 
All adverse events and SAEs will be collected from the signing of the informed consent until 
the final visit at the time points specified in the schedule of assessments (Section 19). 
All SAEs will be recorded and reported to the sponsor or sponsor’s designee within 24 hours, 
as indicated in 69. The investigator will submit any updated SAE data to the sponsor or 
sponsor’s designee within 24 hours of it being available. 
If the investigator learns of any SAE, including a death, at any time after a subject has been 
discharged from the study, and he/she considers the event to be reasonably related to the IMP 
or study participation, the investigator must promptly notify the sponsor or sponsor’s 
designee. 
The method of recording, evaluating, and assessing causality of adverse events and SAEs and 
the procedures for completing and transmitting SAE reports are provided in 69. 
9.4.8.2 
Method of Detecting Adverse Events and SAEs 
The investigator must take care not to introduce bias when detecting adverse events or SAEs. 
Open-ended and non-leading verbal questioning of the subject is the preferred method to 
inquire about adverse event occurrences. 
9.4.8.3 
Follow-up of adverse events and SAEs 
After the initial adverse event or SAE report, the investigator is required to proactively follow 
each subject at subsequent visits/contacts. All SAEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the subject is lost to follow-up. Further 
information on follow-up procedures is given in 69. 
9.4.8.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor or sponsor’s designee of a SAE is 
essential so that legal obligations and ethical responsibilities towards the safety of subjects 
and the safety of an IMP under clinical investigation are met. 


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The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of an IMP under clinical investigation. The sponsor will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB, and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary (see 69). 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then 
file it along with the investigator’s brochure and will notify the IRB, if appropriate according 
to local requirements. 
9.4.8.5 
Pregnancy 
Details of all pregnancies in female subjects and, if indicated, female partners of male 
subjects will be collected after the start of IMP and until the final visit. 
If a pregnancy is reported, the investigator should inform the sponsor or sponsor’s designee 
within 24 hours of learning of the pregnancy and should follow the procedures outlined in 77. 
Pregnancy will not be considered as an adverse event or SAE, but an abnormal outcome (e.g., 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) is 
considered an SAE. 
9.4.9 
Safety review 
An ongoing safety review will also be performed. The decision to go to the next dose group 
will be made by the sponsor. The decision to start dose Group 2 will be based on safety data 
from at least 5 patients on IFX-1 800 mg, and to start Group 3 on at least 5 patients on IFX-1 
1600 mg for at least 1 month. 
9.5 
Immunostaining of biopsy 
At baseline, a small biopsy of the target pyoderma gangrenosum ulcer will be taken and sent 
to a central laboratory. 
9.6 
IFX-1 concentrations 
Blood samples will be collected for measurement of plasma concentrations of IFX-1 as 
specified in the Schedule of Assessments (Section 2). Instructions for the collection and 
handling of biological samples will be provided by the sponsor or sponsor’s designee. The 
actual date and time (24-hour clock time) of each sample will be recorded. 
The plasma concentrations will be used for modeling and simulation. 


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Each plasma sample will be divided into 2 aliquots (1 sample for concentration measurement, 
and 1 sample for back-up). Samples collected for analyses of IFX-1 concentrations may also 
be used to evaluate safety or efficacy aspects related to concerns arising during or after the 
study. 
9.7 
Immunology and other assessments of blood, ulcer fluid, biopsy and 
stool samples 
Venous blood samples will be collected for the measurement of: 
• Anti-drug antibody, antineutrophil cytoplasmic antibody, and antinuclear antibody 
formation 
• Immunology: 
◦ 
 
 
 
 
 
 
 
Fluid draining from the target ulcer, only if wound is open and liquid is available, will be 
collected for analysis of: 
• Immunology: 
◦ 
 
 
 
 
A biopsy will be collected from the border tissue of the target ulcer for analysis for: 
• 
 
 
 
The investigators will be supplied with the necessary sampling tubes 
 etc.) and 
instructed to send the samples to a central laboratory from where they will be forwarded to 
the analyzing laboratories. Further details are given in a laboratory manual. 
Remaining samples will be stored for future research at a suitable storage facility (as 
documented in the trial master file) and analyses may be performed on biomarker variants 
that are later identified. Samples may be used for research to develop methods, assays, 
prognostics and/or companion diagnostics related to the disease process and pathways 
associated with disease state, and/or mechanism of action of the IFX-1. 


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9.8 
Genetic evaluations 
Genetics are not evaluated in this study. 
9.9 
Health Economics 
Health Economics are not evaluated in this study. 
9.10 
Blood Sampling Volumes 
The following table gives an estimation of the blood sampling volumes take during the study. 
These may vary depending on local sampling requirements and techniques. 
 
Table 1 Estimated Blood Sampling Volumes 
Reason for sample 
Number of 
samples 
Volume per sample 
(mL) 
Total volume 
(mL) 
Clinical chemistry (including serology and 
pregnancy test) and hematology 
6 
11.5 mL at Screening 
6.5 mL at other visits 
44 
IFX-1 concentration 
6 
3 
18 
Complement factors 
7 
6 
42 
Other immunology 
7 
3 
21 
QuantiFERON-TB gold test 
1 
4 
4 
Anti-drug antibody 
7 
7 mL at Basaseline,  
5 mL at other visits 
37 
Antineutrophil cytoplasmic antibody and 
antinuclear antibody 
1 
7 
7 
Total: 
 
 
173 
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, will not exceed approximately 200 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples. 
If values are out of range during screening, a single retest is allowed. 
10 
STATISTICAL CONSIDERATIONS 
10.1 
Sample Size Determination 
The sample size for this study is not based on statistical consideration and no formal sample 
size estimation has been performed. In total, 18 subjects will be enrolled in the study. It is 
expected that at least 15 subjects will undergo 3 months treatment (i.e., evaluable). As the 


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study is a pilot study in the indication of pyoderma gangrenosum and conducted as an open 
label study, approximately 5 evaluable subjects per initial dosing group seems to be sufficient 
to explore the safety and tolerability of IFX-1 administered over 189 days to subjects with 
pyoderma gangrenosum. 
10.2 
Analysis Sets 
For purposes of analysis, the following analysis sets are defined: 
Analysis Set 
Description 
Enrolled 
All subjects who sign the ICF 
Safety Set (SAF) 
All subjects who received at least 1 dose of IMP. 
Per Protocol Set (PPS) 
Subjects who completed at least 3 months of treatment and 
who had no major protocol deviation. 
10.3 
Statistical Analyses 
A statistical analysis plan will be developed and finalized before database lock and will 
describe the analysis sets to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data. This section is a summary of the planned statistical 
analyses of the primary and secondary endpoints. 
10.3.1 Safety Analyses 
The primary objective of this study is to explore the safety of IFX-1 administered in subjects 
with pyoderma gangrenosum. Safety will be described by the following endpoints: 
• TEAEs, defined as adverse events that start at or after the first administration of IMP 
• Related TEAEs 
• Serious TEAEs 
• Adverse events of special interest 
TEAEs will be analyzed according to the number and percentage of subjects who had an 
adverse event as well as the number of TEAEs with the respective MedDRA System Organ 
Class and Preferred Term. Related TEAEs and serious TEAEs will be analyzed in the same 
way. Additionally, the number and percentage of subjects with adverse events will be further 
grouped by severity and relationship. The maximum severity/relationship per subject and 
preferred term will be counted in these summary tables. 
All safety analyses will be performed on the SAF. Analyses will generally be performed for 
the entire SAF as well as the 3 dosing groups separately. Additional stratifications based on 
actual dosing and IMP compliance will be defined in the statistical analysis plan. 


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10.3.2 Efficacy Analyses 
The efficacy of IFX-1 for the treatment of skin lesions due to pyoderma gangrenosum is one 
key secondary objective of this study. Further additional clinical outcome measures will also 
be investigated. The efficacy endpoints include: 
• The responder rate based on the Physician’s Global Assessment at Visits V4, V6, 
V10, and V16 (EOT). Response is defined as a Physician’s Global Assessment of ≤3 
at the target ulcer 
• Time to complete closure of pyoderma gangrenosum target ulcer as assessed by the 
investigator 
• Percentage change in wound area and volume assessed by measurement of 
photographs of the target ulcer between selected visits (i.e., change between Visits V1 
and V4, V1 and V6, V6 and V10, V10 and V16, and V1 and V16) 
• Rate of change calculated per day in the area of the target ulcer derived from the 
photographic measurements 
• Number of subjects with a decrease in area of the target ulcer of 50% or more at 
Visit V16 compared to baseline derived from the photographic measurements 
• Number of subjects with a decrease in area of the target ulcer of 100% at Visit V16 
compared to baseline derived from the photographic measurements 
• A wound healing assessment based on the investigators rating of the target ulcer’s 
erythema and border elevation at Visits V4, V6, V10, and V16 (EOT) 
Continuous variables, such as the target ulcer area and ulcer volume, will be analyzed by 
absolute values and changes from baseline, if applicable. Basic descriptive statistics (e.g., 
number of observations (n), mean, standard deviation, minimum, median, maximum, lower 
quartile, upper quartile) will be displayed by visit. All efficacy endpoints will be analyzed 
descriptively only. Therefore, p-values or confidence intervals resulting from possible 
statistical models or tests will be interpreted descriptively only. No statements concerning 
statistical significance are valid. 
The number and percentage of subjects in each category will be displayed by visit for 
categorical or binary variables, such as the responder rate based on the Physician’s Global 
Assessment or the number of subjects with remission. 
The time to complete closure will be analyzed with Kaplan-Meier methods using the date of 
first IMP administration as reference time point. The date of complete closure represents the 
event date. Subjects who do not experience complete closure of the target ulcer will be 
censored at the date of their last assessment. 
All efficacy analyses will be performed on the SAF and on the PPS. Analyses will generally 
be performed for the entire study SAF and PPS as well as the 3 dosing groups separately. 
Additional stratifications based on actual dosing and IMP compliance will be defined in the 


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statistical analysis plan. Additional further details on the statistical analysis will be specified 
in the SAP. 
10.3.3 Pain and Quality of Life Analyses 
Pain will be assessed by a: 
• NRS at Screening, and Visits V1, V4, V6, V10, V16 (EOT), and Ob2 
and quality of life by the: 
• Dermatology Life Quality Index score at Screening, and Visits V1, V4, V6, V10, V16 
(EOT), and Ob2 
Basic descriptive statistics (e.g., number of observations (n), mean, standard deviation, 
minimum, median, maximum, lower quartile, upper quartile) will be displayed for the 
absolute values by visit and for the change of baseline at each visit for each scale. 
The number and percentage of subjects in each answer category will be displayed for each of 
the 10 Dermatology life quality index items. 
All analyses will be conducted on the SAF. Analyses will generally be performed for the 
entire SAF as well as the 3 dosing groups separately. Additional stratifications based on 
actual dosing and IMP compliance will be defined in the statistical analysis plan. 
10.3.4 Analyses of Concentrations of IFX-1 
Concentrations of IFX-1 will be summarized by time point. Derived parameters will be 
analyzed by displaying basic statistics (e.g., number of observations (n), mean, standard 
deviation, coefficient of variation, minimum, median, maximum, geometric mean, geometric 
coefficient of variation). All concentration parameters will be analyzed on the SAF including 
all values and subjects that are assessed as evaluable by the pharmacokinetic specialist. 
Analyses will generally be performed for the entire SAF as well as the 3 dosing groups 
separately. Additional stratifications based on actual dosing and IMP compliance will be 
defined in the statistical analysis plan. 
10.3.5 Other Analyses 
The following parameters will be analyzed descriptively as exploratory endpoints on the 
SAF. 
Safety parameters: 
• Safety laboratory parameters will be analyzed by displaying basic summary statistics 
(e.g., for continuous variables, number of observations (n), mean, standard deviation, 
minimum, median, maximum, lower quartile, upper quartile) for absolute values and 
changes from baseline by visit. 


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• Anti-drug antibody from blood samples at time points described in the Schedule of 
Assessments will be analyzed by the number and percentage of subjects presenting 
anti-drug antibody as per time point. 
• The number of subjects with abnormal physical examination parameters will be 
displayed by visit. 
• Immunology and other assessments on blood, ulcer fluid, biopsies, and stools will be 
analyzed by displaying basic summary statistics. 
10.3.6 Interim Analyses 
Interim analyses will be performed after each initial dosing group of 6 subjects has completed 
Visit V10. The interim analysis will comprise adverse events, Physician’s Global 
Assessment, and photographic documentation of area and volume. 
Statistics for the above parameters will be generated as for the final analysis. 
The statistical analysis plan will describe the planned interim analyses in detail. 
11 
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APPENDICES 




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Appendix 2 
Regulatory and Ethical Considerations 
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
• 
Applicable International Council for Harmonisation Guidelines for GCP 
• 
Applicable laws and regulations 
The protocol, protocol amendments, informed consent form (ICF), investigator’s brochure, 
and other relevant documents (e.g., advertisements) must be submitted to an IRB by the 
investigator and reviewed and approved by the IRB before the study is initiated. 
The study can only start after obtaining a positive evaluation by the applicable IRB and 
approval from the applicable regulatory authority. The written approval of the applicable IRB 
and the responsible regulatory authority must be filed in the trial master file. Additionally, 
each study site must receive a copy of these documents to be filed in the investigator site file. 
Any amendments to the protocol will require IRB approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study subjects. 
The investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB 
• 
Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 CFR, ICH guidelines, the IRB, European regulation 536/2014 for clinical studies 
(if applicable), and all other applicable local regulations 
Financing and Insurance 
The study is financed by the sponsor. 
The subjects are covered by an applicable insurance policy for participation in a clinical 
study. A copy of the insurance policy and the insurance conditions will be filed in the 
investigator site file. 


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Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the course of the study 
and for 1 year after completion of the study. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the study, the purposes, 
the procedures involved, the expected duration, the potential risks and benefits involved, and 
any discomfort it may entail to each study subject or his/her legally authorized representative 
and answer all questions regarding the study. 
Subjects must be informed that their participation is voluntary. Subjects will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB and study site. 
The informed consent must be given by means of standard written statements, written in non-
technical language. The subjects should read the informed consent form and consider their 
decision before signing and dating the document. A copy of the signed document must be 
given to the subject. No subject can be involved in the study if he/she is related to the 
investigator, any member of the team at the study site, or the sponsor. 
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
Subjects must re-consent to the most current version of the ICF during their participation in 
the study. 
A copy of the ICF must be provided to the subject. 
Subjects who are rescreened are required to sign a new ICF. 
Subjects will need to consent to photographical documentation of affected areas. 
Data Protection 
Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 


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The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. 
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
The sponsor will ensure that all safeguards are in place to minimize any eventual risk of 
breaches, and complies otherwise with the requirements of European Union General Data 
Protection Regulation (GDPR, Regulation (EU) 2016/679). The sponsor will regularly check 
all procedures relevant to the processing of personal data, as to ensure privacy by design and 
compliance with GDPR. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before 
submission. This allows the sponsor to protect proprietary information and to provide 
comments. 
The sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 
multisite studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
The sponsor will provide the relevant study protocol information in a public database (e.g., 
ClinicalTrials.gov, https://clinicaltrials.gov/) before or at commencement of the study. The 
sponsor may also provide study information for inclusion in national registries according to 
local regulatory requirements. 
If a potential subject contacts the sponsor regarding participation in the study, the investigator 
agrees that the sponsor may forward the study site and contact details to the subject. Based on 
the inclusion and exclusion criteria for the study, the investigator will assess the suitability of 
the subject for enrollment into the study. 
Results of this study will be disclosed according to the relevant regulatory requirements. All 
publications in peer-reviewed medical journals resulting from this study will be listed in the 
original study protocol registration record (e.g., on ClinicalTrials.gov). 


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Monitoring 
Monitoring of the study sites will be performed by a contract research organization 
designated by the sponsor and will be based on the contract research organization’s 
monitoring standard operating procedures as well as the study specific monitoring manual. 
The clinical monitor, as a representative of the sponsor, has the obligation to follow the study 
closely. The monitor will visit the study site at periodic intervals in addition to maintaining 
necessary telephone calls and written contact as appropriate. The monitor will maintain a 
working knowledge of the study through observation, review of study records and source 
documentation, and discussion of the conduct of the study with the investigator and study site 
personnel. Source data verification of the eligibility criteria as described in the monitoring 
manual will be performed for all subjects. 
The monitor will report via the project manager of the sponsor-designated contract research 
organization to the sponsor who carefully monitors all aspects of the study for compliance 
with applicable government regulations, with respect to current ICH guidelines for GCP and 
current standard operating procedures. 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator 
is responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source data documents. 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during 


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the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
Source Documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data reported on the CRF or entered in the CRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Source data comprise data in medical records, ECG assessments, and wound assessment 
records. 
Audits 
In order to guarantee that the conduct of the study is in accordance with ICH guidelines for 
GCP and the national laws, audits may be performed at the study sites to be carried out by an 
independent auditor. In addition, for-cause audits may be scheduled. 
The investigator agrees to give the auditor access to all relevant documents for review. 
Inspections 
According to the corresponding ICH guidelines for GCP, inspections of the study sites may 
be performed by the local or federal authorities at any time during or after completion of the 
study. 
The investigator agrees to give the inspectors access to all relevant documents for review. 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 


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Reasons for the early closure of a study site by the sponsor or investigator may include but 
are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB or 
local health authorities, the sponsor’s procedures, or GCP guidelines 
• 
Inadequate recruitment of subjects by the investigator 
• 
Discontinuation of further IMP development 
 












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◦ 
Has occurred before administration of the IMP in comparable severity and/or 
frequency 
• Unlikely related (must meet at least first two criteria listed below) 
This category applies to events that are unlikely related to the administration of the IMP. 
The relationship of an event to the sIMP can be considered probably not related if: 
◦ 
The event does not follow a reasonable temporal sequence from 
administration of the drug 
◦ 
The event could readily have been a result of the patient’s clinical state or 
other underlying medical condition environmental or toxic factors, or other 
modes of therapy administered to the patient 
◦ 
The event does not follow a known response pattern to the suspected drug 
◦ 
The event does not reappear or worsen when the IMP is re-administered 
• Possibly related (must meet at least first two criteria listed below) 
This category applies to events that are unlikely to be related to the administration of the 
IMP, but the possibility cannot be ruled-out with certainty. The relationship of an event to 
the IMP can be considered possibly related if: 
◦ 
The event follows a reasonable temporal sequence from administration of the 
IMP 
◦ 
The event could readily have been a result of the patient’s clinical state, 
environmental or toxic factors, or other modes of therapy administered to the 
patient 
◦ 
The event follows a known response pattern to the suspected IMP 
• Probably related (must meet at least first three criteria listed below) 
This category applies to events that are considered with a high degree of certainty to be 
related to the administration of the IMP. The relationship of an event to the IMP drug can 
be considered probably related if: 
◦ 
The event follows a reasonable temporal sequence from administration of the 
IMP 
◦ 
The event could not be reasonably explained by the known characteristics of 
the patient’s clinical state, environmental or toxic factors, or other modes of 
therapy administered to the patient 
◦ 
The event disappears or decreases upon cessation of IMP or reduction in dose 
◦ 
The event follows a known response pattern to the suspected IMP 
• Definitely related (must meet at least first three criteria listed below) 
This category applies to events that are determined with certainty to be related to the 
administration of the IMP. The relationship of an event to the IMP can be considered 
definitely related if: 






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Appendix 4 
Contraceptive Guidance and Collections of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered women of child-bearing potential: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s review of the subject’s medical 
records, medical examination, or medical history interview. 
Postmenopausal female: 
− 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. 
Note: Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-hormonal highly effective contraception methods. 
Contraception Guidance 
Male subjects 
Male subjects who have not had a vasectomy must, during the entire study participation and 
for at least one month after last administration of study drug: 
• either abstain from reproductive sexual intercourse or use a condom during 
intercourse 
• not donate sperm. 
Female subjects 
Female subjects of childbearing potential must not donate eggs and must agree to use a 
highly effective method of contraception consistently and correctly as described in Table 3. 


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Table 3 
Highly Effective Contraceptive Methods 
Note: Subjects must have been on a stable dose of hormonal contraceptives for at least 
4 weeks before Day 1. 
Highly Effective Contraceptive Methods That Are User Dependent a  
(failure rate of <1% per year when used consistently and correctly) 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: b 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly Effective Methods That Are User Independent a 
Implantable progestogen only hormonal contraception associated with inhibition of 
ovulation: b 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner: 
A vasectomized partner is a highly effective contraception method provided that the partner 
is the sole male sexual partner of the woman of child-bearing potential and the absence of 
sperm has been confirmed. If not, an additional highly effective method of contraception 
should be used. 
Sexual abstinence: 
Sexual abstinence is considered a highly effective method only if defined as refraining 
from heterosexual intercourse during the entire period of risk associated with the IMP. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the subject. 


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a Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for subjects 
participating in clinical studies. 
b Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the 
efficacy of the contraceptive method. In this case, two highly effective methods of contraception 
should be utilized during the treatment period and for at least 30 days after the last dose of IMP. 
Pregnancy Testing 
Women of child-bearing potential should only be included after a confirmed menstrual period 
and a negative highly sensitive urine pregnancy test. 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
Collection of Pregnancy Information 
Male Subjects with Partners who Become Pregnant 
The investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. This applies only to 
male subjects who receive IMP. 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours of learning of the partner’s pregnancy. The female 
partner will also be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and child will be forwarded to the sponsor. Generally, the follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of fetal status (presence or absence of anomalies) or 
indication for the procedure. 
Female Subjects who Become Pregnant 
The investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within 24 hours of learning of a subject’s pregnancy. The 
subject will be followed to determine the outcome of the pregnancy. The investigator will 
collect follow-up information on the subject and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
While pregnancy itself is not considered to be an adverse event or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an adverse event or 
SAE. A spontaneous abortion is always considered to be an SAE and will be reported as 


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such. Any post-study pregnancy related SAE considered reasonably related to the IMP by the 
investigator will be reported to the sponsor as described in Section 52. While the investigator 
is not obligated to actively seek this information in former study subjects, he or she may learn 
of an SAE through spontaneous reporting. 
Any female subject who becomes pregnant while participating in the study will discontinue 
IMP. 


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Appendix 5 
Prohibited biologics 
Note: Biologicals used for an underlying disease at a stable dose may be continued. 
Class 
Drug 
Time use 
prohibited before 
screening 
Anti-TNF 
Etanercept 
1 month 
Infliximab, golimumab, certolizumab pegol, 
adalimumab 
3 months 
IL-17 
Brodalumab, ixekizumab, secukinumab 
3 months 
Other biologics 
Ustekinumab 
6 months 
Alefacept, efalizumab, guselkumab, tocilizumab 
3 months 
Tildrakizumab, risankizumab 
5 months 
Briakinumab 
6 months 
Rituximab, alemtuzumab, abatacept, visilizumab, 
natlizumab, belimumab 
12 months 
Anakinra 
1 month 
Systemics 
Apremilast, tofacitinib, methotrexate, cyclosporin, 
azathioprine, thioguanine 
1 month 
 


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Appendix 6 
Permitted wound care 
 
Dressings 
• Foams 
• Superabsorbants 
• Calcium alginate 
• Gelling fibers (hydrofibers) 
Compression therapy 
• Coban2 
• Profore 
• Compression stockings 
• Viscopaste and Easifix 
Antiseptics 
• Iodine derivatives 
• Silver dressings 
• Polyhexamethylene biguanide 
hydrochloride/polyhexanide/polyaminopropyl biguanide 
(PHMB) and Dialkylcarbamoylchloride (DACC) 
 


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Appendix 7 
Amendment 01 
Rationale for Amendment 01 
Amendment 01 was enacted to: 
• Enable the exploration of a dose range of IFX-1 and also to allow the dose to be 
increased in individual patients during study. 
• Increase the number of patients in the study from 12 to a possible 18. 
• Allow screening to take 7 to 35 days instead of 9 to 19 days. 
• Move laboratory tests from screening to the Baseline visit for tests not required for 
screen failures. 
• Add live attenuated vaccination to the list of prohibited medications. 
• Remove analyses of blood and ulcer fluid that will not be performed due to feasibility 
and analytical hurdles of small volumes. 
• Replace incorrect reference to analysis at a local safety laboratory by analysis at a 
central laboratory. 
• Correct the total amount of blood taken. 
• Add contraceptive guidance for male subjects. 
• Standardize definitions of relationship to IMP. 
• Correct inconsistencies in the protocol. 
Corrections to spelling and punctuation are not listed. 
 


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List of changes 
Section 
Original text 
Amended text 
Title page 
Protocol signatures 
10 Synopsis of Study 
Open label exploratory phase IIa trial to 
investigate the safety and efficacy of 
IFX-1 in treating subjects with Pyoderma 
Gangrenosum 
Open label exploratory phase IIa trial to 
investigate the safety and efficacy of IFX-1 
in treating subjects with Pyoderma 
Gangrenosum (OPTIMA) 
Sponsor Signatory: 
Othmar Zenker, MD 
Chief Medical Officer 
Ronald Rosenburg, MD, PhD 
Program Director Dermatology 
Signature of 
Coordinating 
Investigator: 
Afsaneh Alavi MD, Msc, FRCPC 
 
Coordinating Investigator 
Assistant Professor of Dermatology 
 
York Dermatology Center 
250 Harding Blvd. West, 
Suite 312, 
Richmond Hill, 
Ontario, L4C 9M7, 
Canada 
Afsaneh Alavi MD, Msc, FRCPC 
 
Coordinating Investigator 
Assistant Professor of Dermatology 
University of Toronto 
76 Grenville Street 
Toronto, Ontario 
M5S 1B2 
York Dermatology Center 
250 Harding Blvd. West, 
Suite 202, 
Richmond Hill, Ontario 
L4C 9M7, 
Canada 
10 Synopsis of Study 
Rationale 
... Several animal models have 
demonstrated a positive impact of a 
blockade of the C5a/C5aR signaling axis 
on acute and chronic inflammatory 
disease conditions. A recent open label 
study deploying IFX-1 in 12 subjects 
suffering from the chronic dermatologic 
disease hidradenitis suppurativa has 
revealed early evidence of disease 
modifying activity of IFX-1 in this 
neutrophil driven skin disorder. In this 
condition. IFX 1 treatment also leads to 
a sustained clinical response even after 
only 8 weeks of treatment. 
Rationale 
… Several animal models have 
demonstrated a positive impact of a 
blockade of the C5a/C5aR signaling axis 
on acute and chronic inflammatory 
diseases. A recent open label study 
deploying IFX-1 in 12 subjects suffering 
from hidradenitis suppurativa revealed 
early evidence of disease modifying 
activity of IFX-1 in this neutrophil driven 
skin disorder, with a sustained clinical 
response even after only 8 weeks of 
treatment. 
10 Synopsis of Study 
Objectives and Endpoints: 
Occurrence, nature and intensity of 
treatment emergent adverse events 
(TEAEs), related TEAEs, and serious 
TEAEs 
Objectives and Endpoints: 
Occurrence, nature and intensity of 
treatment emergent adverse events 
(TEAEs), related TEAEs, serious TEAEs, 
and adverse events of special interest 
10 Synopsis of Study 
Objectives and Endpoints: 
• Mean change from baseline in pain 
assessed by Numeric Rating Scale (NRS) 
at Visits V4, V6, V10, and V16 (EOT) 
(investigator assessment) 
• Mean change from baseline in 
Dermatology Life Quality Index (DLQI) 
at Visits V4, V6, V10, and V16 (EOT) 
(investigator assessment) 
 
Objectives and Endpoints: 
• Mean change from baseline in pain 
assessed by Numeric Rating Scale (NRS) at 
Visits V4, V6, V10, and V16 (EOT) 
• Mean change from baseline in 
Dermatology Life Quality Index (DLQI) at 
Visits V4, V6, V10, and V16 (EOT) 
10 Synopsis of Study 
Scientific exploratory parameters 
Scientific exploratory parameters 


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Fluid draining from the target ulcer, if 
applicable, for analysis of: 
    • Concentrations of IFX 1 
    • Immunology: 
        ◦ Complement factors C3a, C5a 
        ◦ IL-1beta, IL-6, IL-8, IL-12p40, 
IL-12p19, IL-13, IL-17, IL-36 
        ◦ IFN-a, TNF-alpha 
        ◦ Elastase, calprotectin, other 
matrix metalloproteins 
    • Bacteria using a bacterial culture and 
polymerase chain reaction 
Biopsies will be collected from the 
border tissue of the target ulcer for 
analysis for: 
    • C1q, C3, C5b 9 
    • IL-1beta, IL-6, IL-8, IL-17, IL-36 
    • TNF-alpha 
Fluid draining from the target ulcer, if 
available, for analysis of: 
 
    • Immunology: 
         
        ◦ IL-1beta, IL-6, IL-8, IL-12p40, IL-
12p19, IL-13, IL-17, IL-36 
        ◦ IFN-a, TNF-alpha 
 
 
    • Bacteria using a bacterial culture and 
polymerase chain reaction 
Biopsies will be collected from the border 
tissue of the target ulcer for analysis for: 
 
 
    • IL-1beta, IL-6, IL-8, IL-17, IL-36 
    • TNF-alpha 
10 Synopsis of Study 
Scientific exploratory parameters 
Absolute values and changes from 
baseline will be evaluated for the above 
parameters. 
Scientific exploratory parameters 
Absolute values and changes from the 
baseline value will be evaluated for the 
above parameters. 
10 Synopsis of Study 
Number of Subjects: 
This is planned to be a multi-center study 
with 12 subjects treated with IMP (IFX-
1). 
Subjects discontinuing treatment will not 
be replaced. It is expected that 
approximately 10 subjects will undergo 
at least 3 months treatment. 
Number of Subjects: 
This is planned to be a multi-center study 
with about 18 subjects treated with IMP 
(IFX-1). 
Subjects discontinuing treatment will not 
be replaced. It is expected that 
approximately 15 subjects will undergo at 
least 3 months treatment. 
10 Synopsis of Study 
Treatment Groups and Duration: 
The study duration for an individual 
subject includes screening (14 days 
±5 days), the treatment period (189 days 
±5 days), and the observational follow 
up (60 days ±5 days). 
Treatment Groups and Duration: 
The study duration for an individual subject 
includes screening (14 days range 7 to 
35 days), the treatment period (189 days 
±5 days), and the observational follow up 
(60 days ±5 days). 
10 Synopsis of Study 
Treatment Groups and Duration: 
All subjects will receive 800 mg IFX-1 
per dose (for a maximum of 15 doses in 
total). 
Treatment Groups and Duration: 
All subjects will receive IFX-1 at a 
maximum of 15 dosing visits. 
There will be 3 dosing groups (Group 1, 
Group 2, and Group 3) of 6 subjects each. 
Each group of subjects is recruited 
sequentially. The next dose group will be 
initiated if the previous dose was 
considered safe and well tolerated. If 
dosing in Group 2 cannot be initiated, then 
a further 6 patients will be recruited in 
Group 1. 
10 Synopsis of Study 
Study Population 
Exclusion Criteria: 
5. One of the following abnormal 
laboratory findings at screening: 
Hemoglobin <7 g/mL 
5. One of the following abnormal 
laboratory findings at screening: 
Hemoglobin <7 g/dL 
 
 


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7. No evidence of active tuberculosis on 
a chest X ray taken within 1 year prior to 
screening or a positive QuantiFERON®
TB gold test at screening 
7. Evidence of active tuberculosis 
 
9. An ankle brachial index of less than 
0.8 or toe pressure of less than 80 mmHg 
in subjects with a compromised vascular 
system (e.g., diabetic subjects) at 
screening 
9. An ankle brachial index of less than 0.8 
or toe pressure of less than 80 mmHg in 
subjects with a compromised vascular 
system (e.g., diabetic subjects) within 
previous year or at screening 
 
10. Chronic infection requiring 
suppressive anti-infective therapy (such 
as latent tuberculosis, pneumocystis, 
aspergillosis, cytomegalovirus, herpes 
simplex virus, herpes zoster and atypical 
mycobacteria) 
10. Infection requiring suppressive anti-
infective therapy (such as latent 
tuberculosis, pneumocystis, aspergillosis, 
cytomegalovirus, herpes simplex virus, 
herpes zoster and atypical mycobacteria) 
 
12 Any drug treatment for pyoderma 
gangrenosum including corticosteroids 
(>10 mg), intralesional steroids, 
cyclosporine A, biologicals and 
immunosuppressives (with the exception 
of antibiotics for wound superinfection) 
used within a time of 5 half-lives of the 
drug before screening (see Appendix 5) 
Any drug treatment for pyoderma 
gangrenosum including corticosteroids 
(>10 mg prednisone or prednisone 
equivalent), intralesional steroids, 
cyclosporine A, biologicals and 
immunosuppressives (with the exception of 
antibiotics for wound superinfection) used 
within a time of 5 half-lives of the drug 
before screening (see Appendix 5) 
 
22. Female subjects of childbearing 
potential unwilling to follow the 
contraceptive guidance in Appendix 4 
during the treatment period and for at 
least 30 days after the last dose of IMP 
22. Male and female subjects of 
childbearing potential unwilling to follow 
the contraceptive guidance in Appendix 4 
during the treatment period and for at least 
30 days after the last dose of IMP 
10 Synopsis of Study 
Investigational medical product (IMP), 
dose, and mode of administration 
The IMP will be provided in 10 mL glass 
vials containing 100 mg of IFX 1. For 
each dose, 800 mg of IFX-1 will be 
diluted with approximately 250 ml of 
0.9% sodium chloride and given to the 
subject as a single intravenous dose over 
30 to 60 minutes during a site visit. 
Subjects will receive a total of 15 doses 
of IMP (IFX 1 800 mg). The first 
3 doses will be given in the first week  
on Day 1, Day 4, and Day 8. The 
remaining doses will be given thereafter 
every 2 weeks starting from Day 15. The 
starting dose of IFX 1 is 800mg. 
Investigational medical product (IMP), 
dose, and mode of administration 
The IMP (IFX-1) will be provided in 
10 mL or 20 mL glass vials at a 
concentration of 10 mg/mL (i.e., 100 mg 
per 10 mL vial or 200 mg per 20 mL vial) 
for reconstitution and intravenous 
administration. For each dose, the required 
amount of IFX-1 will be diluted with 0.9% 
sodium chloride to a total volume of 
approximately 250 mL and given to the 
subject as a single intravenous dose over 30 
to 60 minutes during a site visit. 
All subjects will receive IFX-1 800 mg 
three times during the first week (Days 1, 4, 
and 8). 
Starting at Day 15: 
    • Subjects in Group 1 will continue to 
receive IFX-1 800 mg at 2 weekly intervals. 
    • Subjects in Group 2 will receive IFX-1 
1600 mg at 2 weekly intervals. 
    • Subjects in Group 3 will receive IFX-1 
2400 at 2 weekly intervals. 


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At Day 57 (Visit V7), subjects in Groups 
1 and 2 may have their dose increased to 
IFX-1 1600 mg or 2400 mg, respectively, if 
there are no safety concerns and the 
Physician Global Assessment (main 
efficacy parameter) is ≥4. 
Subjects will receive a total of 15 doses of 
IFX-1. The first 3 doses will be given in the 
first week on Day 1, Day 4, and Day 8. The 
remaining doses will be given thereafter 
every 2 weeks starting from Day 15. 
10 Synopsis of Study 
Statistical methods 
… 
An interim analysis will be performed on 
a minimum of 6 subjects who complete 
Visit V10 at Day 99 to assess the 
progress of the study. 
 
... 
Statistical methods 
... 
Interim analyses will be performed after 
each initial dosing group of 6 subjects has 
completed Visit V10. The interim analysis 
will comprise adverse events, Physician’s 
Global Assessment, and photographic 
documentation of area and volume. 
… 
Statistical analyses will generally be 
performed for the entire study population 
as well as the 3 dosing groups separately. 
Additional stratifications based on actual 
dosing and IMP compliance will be defined 
in the statistical analysis plan. 
19 Schedule of 
Assessments 
Screening Visit V0 Day -14 
±5 
Screening Visit V0 Day 14 
7 to 35 
 
Visit V15 Day 179 
Visit V15 Day 169 
 
 
[Tx: Added dose modification for visit V7] 
[Safety: Added Chest X-ray at Visit V0] 
[Moved all biomarkers from Screening to 
Visit V1] 
[Deleted measurement of antinuclear 
antibody from all but Visit V1] 
 
Footnotes 
b Subjects with a compromised 
vascular system (e.g., diabetic subjects) 
 
Footnotes 
b Subjects with a compromised vascular 
system (e.g., diabetic subjects), within 
previous year or at screening 
[added footnote “d” for Visit V2: 
d Only for subjects in Group 1 and Group 
2] 
21 Study Rationale 
Neutrophilic dermatoses are a spectrum 
of inflammatory disorders characterized 
by skin lesions resulting from a 
neutrophil-rich inflammatory infiltrate in 
the absence of infection. The exact 
molecular pathophysiology of the 
neutrophilic dermatoses has long been 
poorly understood. Interestingly, 
neutrophil-rich cutaneous inflammation 
is also a cardinal feature of several auto-
inflammatory diseases with skin 
Neutrophilic dermatoses are a spectrum of 
inflammatory disorders characterized by 
skin lesions resulting from a neutrophil-rich 
inflammatory infiltrate in the absence of 
infection. Neutrophil-rich cutaneous 
inflammation is also a cardinal feature of 
several auto-inflammatory diseases with 
skin involvement, the latter being caused 
by aberrant innate immune responses. 


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involvement, the latter being caused by 
aberrant innate immune responses. 
22 IFX-1 
IFX-1 is an IMP and is not approved in 
any country worldwide. To date, IFX-1 
has been investigated in 1 Phase I study 
in healthy subjects and in 3 Phase II 
studies in subjects with early septic 
organ dysfunction, in subjects 
undergoing complex cardiac surgery, and 
in subjects with moderate to severe 
hidradenitis suppurativa. 
 
 
 
 
 
 
 
… 
Further details on IFX-1 are given in the 
Investigator’s Brochure, the current 
version of which is available in the 
investigator site file. 
IFX-1 is an IMP and is not approved in any 
country worldwide. To date, IFX-1 has 
been investigated in 1 Phase I study in 
healthy subjects and in 4 Phase II studies in 
subjects with early septic organ 
dysfunction, in subjects undergoing 
complex cardiac surgery, and in subjects 
with moderate to severe hidradenitis 
suppurativa: 
… 
Study IFX-1-P2.4 (subjects with moderate 
to severe hidradenitis suppurativa): in this 
Phase II study, 177 subjects were treated 
with either placebo or one of 4 different 
dose regimens of IFX-1 (400 or 800 mg 
every four weeks and 800 or 1200 mg every 
two weeks). The IFX-1 treatment was well 
tolerated and although most subjects 
experienced TEAEs, these were for the 
most part non-serious and similar in all 
treatment groups. IFX-1 treatment was 
associated with low immunogenicity. 
Further details on IFX-1 are given in the 
investigator’s brochure (the current version 
is available in the investigator site file). 
24 Rationale for 
Dosing Regimen 
Like hidradenitis suppurativa, pyoderma 
gangrenosum is also considered to be a 
leukocytosis driven auto-inflammatory 
disease. As a dose of 800 mg was 
efficacious in this subject population, it 
is likely that the same dose could also be 
efficacious in pyoderma gangrenosum 
with the same auto-inflammatory 
pathology. Therefore this dose will be 
used in this study. 
Like hidradenitis suppurativa, pyoderma 
gangrenosum is also considered to be a 
neutrophil driven auto-inflammatory 
disease. As a dose of 800 mg was 
efficacious in the subject population of 
IFX-1-P2.3, it is likely that the same dose 
could also be efficacious in pyoderma 
gangrenosum with the same auto-
inflammatory pathology. Therefore, this 
dose is used as the starting dose in this 
study. 
However, a recently completed Phase II 
study in moderate to severe hidradenitis 
suppurativa indicates that higher doses 
may be necessary to treat leukocytosis in 
the skin. In this study IFX-1-P2.4 (SHINE), 
177 patients were treated with either 
placebo or one of 4 different dose regimens 
of IFX-1. The study failed to meet its 
primary endpoint, a dose-dependent drug 
effect on the HS Clinical Response Score 
(HiSCR) after 16 weeks of treatment. The 
percentages of subjects with HiSCR were 
similar in all dose groups, with 46.0% for 
placebo, 38.1% for 400 mg every four 
weeks, 48.6% for 800 mg every four weeks, 
35.9% for 800 mg every two weeks, and 
45.0% for 1200 mg every two weeks. 


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However, there was a statistically 
significant reduction of draining fistulas 
relative to baseline in the high dose IFX-1 
group when compared to placebo (63.2% 
vs 18.0% reduction; p=0.0359) at week 16. 
In addition, the total abscess and 
inflammatory nodule count was reduced 
compared to placebo in all IFX-1 treatment 
groups (26.5% reduction under placebo 
and 32.7%, 54.6%, 44.9%, 47.7% 
respectively in the IFX-1 groups). 
Abscesses (20.4% reduction under placebo 
vs 31.1% reduction under high dose at 
week 16) and inflammatory nodule counts 
(30.7% reduction under placebo vs 40.7% 
reduction under high dose at week 16) were 
also reduced over time. Hence, although 
the primary endpoint was not met, 
additional post-hoc analyses of the 
obtained data at week 16 indicate a robust 
anti-inflammatory activity in the high dose 
IFX-1 treatment group across numerous 
efficacy measures. 
Therefore, in this study (IFX-1-P2.7), the 
dose of 800 mg every 2 weeks in Group 1 is 
lower than the effective dose in IFX-1-P2.3 
which was 800 mg every week. It is also 
lower than effective dose in IFX-1-P2.4, 
which was 1200 mg every two weeks. 
Population/pharmacokinetic analyses and 
simulations of data from the IFX-1-P2.3 
and 
IFX-1-P2.4 studies showed a well-defined 
dose exposure relationship across doses of 
400, 800, 1200, 1600, 2000, 2400, 2800, 
and 3200 mg, given every 2 or 4 weeks. 
These analyses show that after 16 weeks 
(112 days) of treatment, only 55% of 
simulated patients were above the critical 
efficacy exposure when given 800 mg IFX-
1 every 2 weeks. In contrast, 99% of 
simulated patients were above the critical 
exposure if treated with 2400 mg IFX-1 
every 2 weeks. At this dose, only 0.3% and 
0.1% of simulated patients were above the 
steady state AUC and Cmax NOAEL 
values, respectively. 
The time to ulcer healing in pyoderma 
gangrenosum varies in different trials of 
infliximab and other biologicals (Foss et al. 
2008, Adişen et al. 2008, Foss et al. 2008, 
Brooklyn et al. 2006, Guenova et al. 2011, 
Kolios et al. 2015). However, an effect is 
likely to be seen after 6 to 8 weeks of 
treatment. The time to healing seems to 
correlate to ulcer size and is considered to 


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be less than 2 months for ulcers smaller 
than 6 cm2. 
Therefore, this study will explore IFX-1 
doses of 800 mg, 1600 mg, and 2400 mg 
given every 2 weeks. All doses are covered 
by the NOAEL of 50 mg/mL 
27 Overall Design 
Figure 1 Study Design 
 
Figure 1 Study Design 
[New flow chart inserted to include dose 
groups and dose modification] 
27 Overall Design 
The allowed time windows for Visits V1 
to V6 are ±2 days. All other visits have 
allowed time windows of ±5 days. 
The allowed time windows for Visits V1 
to V6 are ±2 days. All other visits have 
allowed time windows of ±5 days. There 
must be at least 48 hours between each 
dose of IFX-1 (Section 7.1.9). Visits should 
be scheduled appropriately. 
29 Study Sites, Study 
Subject, and Expected 
Duration 
This study is planned to be a multi-center 
study with 12 subjects treated with IMP 
(IFX-1). 
... 
The study duration for an individual 
subject includes screening (14 days 
±5 days), the treatment period (189 days 
±5 days), and the observational follow 
up (60 days ±5 days). 
This study is planned to be a multi-center 
study with about 18 subjects treated with 
IMP (IFX-1). 
… 
The study duration for an individual subject 
includes screening (14 days range 7 to 
35 days), the treatment period (189 days 
±5 days; the last day of dosing of IFX-1 is 
Day 169), and the observational follow up 
(60 days ±5 days). 
30 Screening Failures 
Re-screened subjects will be reported 
with the same subject number as for the 
initial screening. 
Re-screened subjects will receive the next 
available subject number. 
30 Treatment 
Administered 
Unit dose strength(s)/ Dosage level(s): 
10 mL glass vials at a concentration of 
10 mg/mL (total 100 mg per vial) 
 
Dosing instructions: IFX-1 800 mg will 
be diluted with approximately 250 ml of 
0.9% sodium chloride and given as a 
single intravenous dose over 30 to 
60 minutes 
 
Packaging and labeling: 
The cartons will be labeled with a unique 
(medication) number (“medcode”). The 
vials within a carton will be labeled with 
the same (medication) number as the 
carton in which they are packed. 
The labels are part of the Clinical Trial 
Application documentation. 
 
Manufacturer: 
Celonics on behalf of InflaRx 
Unit dose strength(s)/ Dosage level(s): 
10 mL and 20 mL glass vials at a 
concentration of 10 mg/mL 
 
Dosing instructions: The required dose of 
IFX-1 will be diluted with 0.9% sodium 
chloride to a total volume of approximately 
250 ml and given as a single intravenous 
dose over 30 to 60 minutes 
 
The cartons will be labeled with a unique 
number (medication or kit number). The 
vials within a carton will be labeled with 
the same (medication) number as the carton 
in which they are packed. 
 
Manufacturer: 
Celonics and WuXi on behalf of InflaRx 
31 Dosing groups 
No dose modification of IFX 1 is 
foreseen in this study. 
There will be 3 dosing groups (Group 1, 
Group 2, and Group 3) of 6 subjects each. 
Each group of subjects is recruited 
sequentially. The next dose group will be 


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initiated if the previous dose was 
considered safe and well tolerated. If 
dosing in Group 2 cannot be initiated, then 
a further 6 patients will be recruited in 
Group 1. 
All subjects will receive IFX-1 800 mg 
three times during the first week (Days 1, 4, 
and 8). 
Starting at Day 15: 
    • Subjects in Group 1 will continue to 
receive IFX-1 800 mg at 2 weekly intervals. 
    • Subjects in Group 2 will receive IFX-1 
1600 mg at 2 weekly intervals. 
    • Subjects in Group 3 will receive IFX-1 
2400 at 2 weekly intervals. 
At Day 57 (Visit V7), subjects in Groups 
1 and 2 may have their dose increased to 
IFX-1 1600 mg or 2400 mg, respectively, if 
there are no safety concerns and the 
Physician Global Assessment (main 
efficacy parameter) is ≥4. 
32 Preparation and 
administration 
The IMP will be prepared at the study 
site or site pharmacy under controlled 
conditions and in compliance with rules 
governing preparations. The amount of 
IMP for a single infusion is 800 mg IFX
1. The IMP will be diluted in sterile 
sodium chloride. The total volume in the 
infusion bag for each infusion should be 
approximately 250 mL. Details of IMP 
preparation and application will be 
outlined in the pharmacy manual. 
The IFX-1 for infusion will be reconstituted 
(prepared) under controlled conditions at 
the study site or at the study site’s 
pharmacy, in accordance with local 
regulations/ requirements for aseptic 
reconstitution. 
The IMP will be diluted in sterile sodium 
chloride. The total volume in the infusion 
bag for each infusion should be 
approximately 250 mL. 
The reconstituted IFX-1 should be used 
within 4 hours after dilution when stored at 
room temperature. Otherwise, the 
reconstituted IFX-1 has to be stored at 2°C 
to 8°C (35.6°F to 46.4°F) and used within 
24 hours; if the reconstituted IFX-1 
solution is stored in a fridge, it must be left 
to acclimatize to room temperature prior to 
administration. Details on reconstituting 
the IFX-1 will be provided in the Pharmacy 
Manual. 
The number of unused, partially used, and 
empty vials will be documented accurately, 
and the vials will be kept at the site until 
the drug accountability documentation has 
been checked by the study monitor (Section 
7.1.7). 
32 Preparation and 
administration 
The IMP will be infused over a period of 
30 to 60 minutes (± 10 min) via an 
intravenous line. Sites may use their own 
intravenous lines. 
The IMP will be infused intravenously over 
a period of 30 to 70 minutes via an 
intravenous line. Sites should use the 
supplied intravenous lines. 
34 Overdose of IMP 
For this study, any dose of IFX 1 greater 
than 800 mg within a 2 day time period 
At least 48 hours must have elapsed 
between each dose of IFX-1. Visits should 


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will be considered an overdose. The 
consequences of an overdose with IFX-1 
are not known. InflaRx does not 
recommend specific treatment for an 
overdose. 
 
 
 
… 
2. Closely monitor the subject for any 
adverse events or SAEs and laboratory 
abnormalities for at least 7 days. 
be scheduled appropriately. Any second 
administration within this time, or any 
administration that is greater than the 
scheduled dose will be considered an 
overdose. The consequences of an overdose 
with IFX-1 are not known. InflaRx does 
not recommend specific treatment in case 
of an overdose. 
… 
2. Closely monitor the subject for any 
adverse events or SAEs and laboratory 
abnormalities for at least 7 days. If more 
than 130% of the dose is given, the patient 
should be kept in hospital overnight. 
35 Allowed 
Concomitant Therapy 
Wound care for pyoderma gangrenosum 
 
Further details of wound care are given 
in Appendix 6. 
… 
Standard compression therapy 
throughout the study is required. 
Wound care for pyoderma gangrenosum 
Wound care is performed at the scheduled 
visits, and 2 to 3 times a week depending 
on necessity according to the standard of 
care. 
Further details of wound care are given in 
Appendix 6. 
… 
Standard compression therapy throughout 
the study is required (Shavit and Alavi 
2019). 
35 Prohibited Therapy The following therapies are prohibited 
for all subjects from screening until 
Visit EOT or discontinuation from the 
study: 
 
… 
Oral or injectable corticosteroids 
 
… 
Over-the-counter topical antiseptic 
washes, creams, soaps, ointments, gels, 
and liquids containing antibacterial 
agents to treat pyoderma gangrenosum 
The following therapies are prohibited for 
all subjects from screening until Visit EOT 
or discontinuation from the study: 
Subject has received a live attenuated 
vaccine within 3 months prior to screening 
or plans to receive a live attenuated 
vaccine during the study or up to 4 weeks 
after the last study product administration. 
… 
Oral or injectable corticosteroids (more 
than 10 mg prednisone or prednisone 
equivalent) 
… 
Over-the-counter topical antiseptic washes, 
creams, ointments, gels, and liquids 
containing antibacterial agents to treat 
pyoderma gangrenosum 
38 Screening 
The screening procedures will be 
conducted within 14 days (±5 days) 
before first administration of IMP. 
The screening procedures will be 
conducted within 14 days (range 7 to 
35 days) before first administration of IMP. 
38 Screening 
The following procedures will be 
conducted and documented at the 
Screening visit: 
… 
    • Measure ankle brachial index/toe 
pressure in subjects with a compromized 
cardiovascular system 
    • Record a 12 lead ECG 
 
The following procedures will be 
conducted and documented at the 
Screening visit: 
 
… 
    • Measure ankle brachial index/toe 
pressure in subjects with a compromized 
cardiovascular system (unless performed in 
the previous year) 


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    • Take blood for 
        ◦ Safety laboratory parameters 
(clinical chemistry and hematology) 
        ◦ Human immunodeficiency virus, 
hepatitis B virus, and hepatitis C virus 
test 
        ◦ Pregnancy test for women of 
childbearing potential 
        ◦ QuantiFERON-TB gold test for 
the presence of tuberculosis 
        ◦ Immunology 
        ◦ Anti drug antibody, antineutrophil 
cytoplasmic antibody, and antinuclear 
antibody 
    • Take a sample of the target ulcer 
fluid, if applicable 
    • Take a biopsy of the target ulcer 
    • Take urine for urinalysis 
    • Record a 12 lead ECG 
    • Chest X-ray 
    • Take blood for 
        ◦ Safety laboratory parameters 
(clinical chemistry and hematology) 
        ◦ Human immunodeficiency virus, 
hepatitis B virus, and hepatitis C virus test 
        ◦ Pregnancy test for women of 
childbearing potential 
        ◦ QuantiFERON-TB gold test for the 
presence of tuberculosis 
    • Take urine for urinalysis 
40 Start of IMP: Visit 
V1 (Day 1) 
The following will be performed at Visit 
V1: 
… 
    • Record a 12 lead ECG 
    • Perform a urine pregnancy test for a 
woman of childbearing potential 
The following will be performed at Visit 
V1: 
… 
    • Record a 12 lead ECG 
    • Take blood for 
        ◦ Immunology 
        ◦ Anti-drug antibody, antineutrophil 
cytoplasmic antibody, and antinuclear 
antibody 
    • Take a sample of the target ulcer fluid 
if wound is open and liquid is available 
    • Take a biopsy of the target ulcer 
    • Perform a urine pregnancy test for a 
woman of childbearing potential 
41 Treatment visit V7 [New section] 
9.1.3.1 Treatment visit V7 
In addition to the assessments and 
procedures outlined in the Schedule of 
Assessments (Section 2), the dose of IFX-1 
will be assessed and increased in subjects 
of Group 1 and Group 2 if the dose 
escalation criteria are met (Section 7.1.2). 
41 Treatment visits 
(Visits V4 and V6) 
42 Mid visit: Visit 
V10 
43 End of treatment 
visit: Visit 16 (Day 
189) 
Take a sample of the target ulcer fluid, if 
applicable 
Take a sample of the target ulcer fluid if 
wound is open and liquid is available 
43 End of treatment 
visit: Visit 16 (Day 
189) 
Take a biopsy of the target ulcer 
Use a standard dressing and compression 
therapy for the target ulcer 
 
Use a standard dressing and compression 
therapy for the target ulcer 
41 Treatment visits 
(Visits V4 and V6) 
    • Take blood for 
        ... 
   • Take blood for 
        ... 
        ◦ Anti-drug antibody 


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42 Mid visit: Visit 
V10 
43 End of treatment 
visit: Visit 16 (Day 
189) 
44 Visit Ob1 (End of 
treatment +30 days) 
44 Final Visit (End of 
Trial): Visit Ob2 (End 
of treatment +60 days) 
 
        ◦ Anti-drug antibody, antineutrophil 
cytoplasmic antibody, and antinuclear 
antibody 
47 Dermatology Life 
Quality Index 
To avoid biasing the subject’s response, 
the subject should complete the 
questionnaire in the diary at the study 
site before study site personnel perform 
any other assessments and before any 
interaction with the study site personnel 
has occurred. 
To avoid biasing the subject’s response, the 
subject should complete the questionnaire 
at the study site before study site personnel 
perform any other assessments and before 
any interaction with the study site 
personnel has occurred. 
48 Numeric Rating 
Scale for Pain 
It is an 11-point scale (from 0 represent 
no pain to 10 representing the worst pain 
the subject can imagine). Subjects are 
asked to rate the intensity of their pain 
“right now” verbally with a number or 
by pointing to the number that represents 
their pain intensity. 
It is an 11-point scale (from 0 represent no 
pain to 10 representing the worst pain the 
subject can imagine). Subjects are asked to 
rate the intensity of their pain “right now” 
verbally with a number. 
48 Safety Assessments Safety will be assessed on the basis of 
the following variables: 
The following safety variables will be 
collected: 
… 
Chest X-ray 
48 Safety Laboratory 
Assessments 
The safety laboratory assessments will 
be performed by a local laboratory. 
Urinalysis will be locally performed 
using a dipstick. 
The safety laboratory assessments will be 
performed by a central laboratory. 
Urinalysis will be centrally performed 
using a dipstick. 
50 12-lead 
electrocardiograms 
Digital ECG wave forms will be 
centrally archived. 
 
50 Physical 
Examination 
A brief physical examination will 
include, at a minimum, assessments of 
the skin, lungs, cardiovascular system, 
and abdomen (liver and spleen). 
 
50 Adverse events 
The definitions of an adverse event or 
SAE can be found in Appendix 3. 
… 
The investigator and any designees are 
responsible for detecting, documenting, 
and recording events that meet the 
definition of an adverse events or SAE. 
They are responsible for following up 
adverse events that are serious, 
considered related to the IMP or study 
procedures, or that caused the subject to 
discontinue the IMP or study. 
The definitions of an adverse event, 
adverse event of special interest, and SAE 
can be found in Appendix 3. 
… 
The investigator and any designees are 
responsible for detecting, documenting, 
recording, and reporting (to the sponsor) 
adverse events, adverse events of special 
interest, or SAEs. They are also 
responsible for following up all adverse 
events until their resolution or until a 
steady state of the event is reached. 


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51 Time Period and 
Frequency for 
Collecting adverse 
events and SAE 
Information 
Investigators are not obligated to actively 
seek adverse event or SAE information 
from former study subjects. However, if 
the investigator learns of any SAE, 
including a death, at any time after a 
subject has been discharged from the 
study, and he/she considers the event to 
be reasonably related to the IMP or study 
participation, the investigator must 
promptly notify the sponsor or sponsor’s 
designee. 
If the investigator learns of any SAE, 
including a death, at any time after a 
subject has been discharged from the study, 
and he/she considers the event to be 
reasonably related to the IMP or study 
participation, the investigator must 
promptly notify the sponsor or sponsor’s 
designee. 
[9.4.8] Chest X-ray 
[New section] 
A standard chest X-ray will be performed 
at screening. 
52 Safety review 
[New section] 
An ongoing safety review will also be 
performed. The decision to go to the next 
dose group will be made by the sponsor. 
The decision to start dose Group 2 will be 
based on safety data from at least 
5 patients on IFX-1 800 mg, and to start 
Group 3 on at least 5 patients on IFX-1 
1600 mg for at least 1 month. 
52 Immunostaining of 
biopsy 
At screening, a small biopsy of the target 
pyoderma gangrenosum ulcer will be 
taken and sent to a central laboratory for 
immunostaining. 
At baseline, a small biopsy of the target 
pyoderma gangrenosum ulcer will be taken 
and sent to a central laboratory. 
53 Immunology and 
other assessments of 
blood, ulcer fluid, 
biopsies and stool 
samples 
Venous blood samples will be collected 
for the measurement of: 
... 
Fluid draining from the target ulcer, if 
applicable, will be collected for analysis 
of: 
    • Immunology: 
        ◦ Complement factors C3a, C5a 
        ◦ IL-1beta, IL-6, IL-8, IL-12p40, 
IL-12p19, IL-13, IL-17, IL-36 
        ◦ IFN-a, TNF-alpha 
        ◦ Elastase, calprotectin, other 
matrix metalloproteins 
    • Bacteria using a bacterial culture and 
polymerase chain reaction 
Biopsies will be collected from the 
border tissue of the target ulcer for 
analysis for: 
    • C1q, C3, C5b 9 
    • IL-1beta, IL-6, IL-8, IL-17, IL-36 
    • TNF-alpha 
Venous blood samples will be collected for 
the measurement of: 
… 
Fluid draining from the target ulcer, only if 
wound is open and liquid is available, will 
be collected for analysis of: 
    • Immunology: 
        
        ◦ IL-1beta, IL-6, IL-8, IL-12p40, IL-
12p19, IL-13, IL-17, IL-36 
        ◦ IFN-a, TNF-alpha 
 
    • Bacteria using a bacterial culture and 
polymerase chain reaction 
A biopsy will be collected from the border 
tissue of the target ulcer for analysis for: 
 
    • IL-1beta, IL-6, IL-8, IL-17, IL-36 
    • TNF-alpha 
53 Immunology and 
other assessments of 
blood, ulcer fluid, 
biopsies and stool 
samples 
Complement factors C3a and C5a will be 
analyzed at InflaRx with an ELISA test 
system. All other analyses will be 
performed by a specialized laboratory. 
Samples will be stored and analyses may 
be performed on biomarker variants that 
are later identified. 
The investigators will be supplied with the 
necessary sampling tubes (citrate, EDTA 
etc.) and instructed to send the samples to a 
central laboratory from where they will be 
forwarded to the analyzing laboratories. 
Further details are given in a laboratory 
manual. 


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Remaining samples will be stored for future 
research at a suitable storage facility (as 
documented in the trial master file) and 
analyses may be performed on biomarker 
variants that are later identified. 
54 Blood Sampling 
Volumes 
 
Estimated Blood Sampling Volumes 
Total 221 
The maximum amount of blood collected 
from each subject over the duration of 
the study, including any extra 
assessments that may be required, will 
not exceed approximately 250 mL. 
[Sample volumes for tests amended] 
Estimated Blood Sampling Volumes 
Total 173 
The maximum amount of blood collected 
from each subject over the duration of the 
study, including any extra assessments that 
may be required, will not exceed 
approximately 200 mL. 
54 Sample Size 
Determination 
The sample size for this study is not 
based on statistical consideration and no 
formal sample size estimation has been 
performed. In total, 12 subjects will be 
enrolled in the study. It is expected that 
at least 10 subjects will undergo 
3 months treatment (i.e., evaluable). As 
the study is a pilot study in the indication 
of pyoderma gangrenosum and 
conducted as an open label study, 
approximately 10 evaluable subjects 
seems to be sufficient to explore the 
safety and tolerability of IFX-1 
administered over 189 days to subjects 
with pyoderma gangrenosum. 
The sample size for this study is not based 
on statistical consideration and no formal 
sample size estimation has been performed. 
In total, 18 subjects will be enrolled in the 
study. It is expected that at least 15 subjects 
will undergo 3 months treatment (i.e., 
evaluable). As the study is a pilot study in 
the indication of pyoderma gangrenosum 
and conducted as an open label study, 
approximately 5 evaluable subjects per 
initial dosing group seems to be sufficient 
to explore the safety and tolerability of 
IFX-1 administered over 189 days to 
subjects with pyoderma gangrenosum. 
55 Safety Analyses 
The primary objective of this study is to 
explore the safety of IFX-1 administered 
in subjects with pyoderma gangrenosum. 
Safety will be described by the following 
endpoints: 
    • TEAEs, defined as adverse events 
that start at or after the first 
administration of IMP 
    • Related TEAEs 
    • Serious TEAEs 
… 
All safety analyses will be performed on 
the safety analysis set. 
The primary objective of this study is to 
explore the safety of IFX-1 administered in 
subjects with pyoderma gangrenosum. 
Safety will be described by the following 
endpoints: 
    • TEAEs, defined as adverse events that 
start at or after the first administration of 
IMP 
    • Related TEAEs 
    • Serious TEAEs 
    • Adverse events of special interest 
… 
All safety analyses will be performed on 
the SAF. Analyses will generally be 
performed for the entire SAF as well as the 
3 dosing groups separately. Additional 
stratifications based on actual dosing and 
IMP compliance will be defined in the 
statistical analysis plan. 
56 Efficacy Analyses 
All efficacy analyses will be performed 
on the SAF and on the PPS. 
Further details on the statistical analysis 
will be specified in the SAP. 
All efficacy analyses will be performed on 
the SAF and on the PPS. Analyses will 
generally be performed for the entire study 
SAF and PPS as well as the 3 dosing 
groups separately. Additional 
stratifications based on actual dosing and 
IMP compliance will be defined in the 


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statistical analysis plan. Additional further 
details on the statistical analysis will be 
specified in the SAP. 
57 Pain and Quality of 
Life Analyses 
All analyses will be conducted on the 
SAF. 
All analyses will be conducted on the SAF. 
Analyses will generally be performed for 
the entire SAF as well as the 3 dosing 
groups separately. Additional 
stratifications based on actual dosing and 
IMP compliance will be defined in the 
statistical analysis plan. 
57 Analyses of 
Concentrations of 
IFX-1 
All concentration parameters will be 
analyzed on the SAF including all values 
and subjects that are assessed as 
evaluable by the pharmacokinetic 
specialist. 
All concentration parameters will be 
analyzed on the SAF including all values 
and subjects that are assessed as evaluable 
by the pharmacokinetic specialist. Analyses 
will generally be performed for the entire 
SAF as well as the 3 dosing groups 
separately. Additional stratifications based 
on actual dosing and IMP compliance will 
be defined in the statistical analysis plan. 
58 Interim Analyses 
An interim analysis will be performed on 
a minimum of 6 subjects on their data up 
to Visit 10. The interim analysis will 
comprise adverse events, physicians 
global assessment, and photographic 
documentation of area and volume. 
Interim analyses will be performed after 
each initial dosing group of 6 subjects has 
completed Visit V10. The interim analysis 
will comprise adverse events, Physician’s 
Global Assessment, and photographic 
documentation of area and volume. 
58 References 
[References added] 
Adişen E, Oztaş M, Gürer MA. Treatment 
of idiopathic pyoderma gangrenosum with 
infliximab: induction dosing regimen or on-
demand therapy? Dermatology (Basel) 
2008; 216(2): 163–5. 
 
Brooklyn TN, Dunnill MGS, Shetty A, 
Bowden JJ, Williams JDL, Griffiths CEM, 
et al. Infliximab for the treatment of 
pyoderma gangrenosum: a randomised, 
double blind, placebo controlled trial. Gut 
2006; 55(4): 505–9. 
 
Guenova E, Teske A, Fehrenbacher B, 
Hoerber S, Adamczyk A, Schaller M, et al. 
Interleukin 23 expression in pyoderma 
gangrenosum and targeted therapy with 
ustekinumab. Arch Dermatol 2011; 
147(10): 1203–5. 
 
Shavit E, Alavi A. Compression therapy for 
non-venous leg ulcers: Current viewpoint. 
Int Wound J 2019. 
69 Adverse Events: 
Definitions and 
Procedures for 
Recording, Evaluation, 
Definition of an Adverse Event 
An adverse event is any untoward 
medical occurrence in a patient or 
clinical study subject, temporally 
Definition of an Adverse Event 
An adverse event is any untoward medical 
occurrence in a patient or clinical study 
subject, whether or not considered related 
to the IMP. 


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Follow-up, and 
Reporting 
associated with the use of IMP, whether 
or not considered related to the IMP. 
NOTE: An adverse event can therefore 
be any unfavorable and unintended sign 
(including an abnormal laboratory 
finding), symptom, or disease (new or 
exacerbated) temporally associated with 
the use of IMP. 
NOTE: An adverse event can therefore be 
any unfavorable and unintended sign 
(including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated). 
Treatment emergent adverse events are 
adverse events that are temporally 
associated with the use of IMP. 
69 Adverse Events: 
Definitions and 
Procedures for 
Recording, Evaluation, 
Follow-up, and 
Reporting 
Appendix 3 Adverse Events: Definitions 
and Procedures for Recording, 
Evaluation, Follow-up, and Reporting 
 
Situations in which an untoward medical 
occurrence did not occur (social and/or 
convenience admission to a hospital). 
Appendix 3 Adverse Events: Definitions 
and Procedures for Recording, Evaluation, 
Follow-up, and Reporting 
 
Situations in which an untoward medical 
occurrence did not occur (social and/or 
convenience admission to a hospital) or 
planned hospitalizations due to a pre-
existing condition that has not worsened 
(e.g., elective surgery). 
69 Adverse Events: 
Definitions and 
Procedures for 
Recording, Evaluation, 
Follow-up, and 
Reporting 
[New section] 
Definition of an adverse events of special 
interest 
An adverse event of special interest is an 
adverse event of scientific and medical 
concern specific to the sponsor’s product 
or program, for which ongoing monitoring 
and rapid communication by the 
investigator to the sponsor could be 
appropriate. Such an event might require 
further investigation in order to 
characterize and understand it. 
    • Infusion-related reactions, including 
acute and delayed hypersensitivity and 
anaphylactic reactions during or after IFX-
1 infusion 
All patients should be observed closely 
during the IFX-1 administration and for 
30 minutes after the first 2 infusions. The 
IV line should remain open during the 
observation to allow for administration of 
IV drugs, if necessary. Medication for 
infusion-related reactions should be 
available for immediate use. Medical staff 
have to be trained in resuscitation and 
immediate intensive care has to be readily 
accessible in case of severe life-threatening 
events. Mild to moderate reactions may be 
treated by slowing or interruption of the 
infusion, or with supportive treatment. 
For any potential infusion-related event, 
the investigator should check for a 
potentially developing or existing 
anaphylactic reaction. If an anaphylactic 
reaction is possible, appropriate immediate 
actions should be taken according to the 
severity or stage of the detected 
anaphylactic reaction as recommended by 


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existing guidelines for the treatment of 
anaphylactic reactions or, if established at 
the study sites, according to available 
standard operating procedures or other 
algorithms. 
    • Meningitis 
If there are signs of meningitis at any time 
during the study, the IMP should be 
discontinued if meningitis is confirmed. The 
patient must be closely monitored and the 
guidelines for treatment of meningitis 
should be followed. This includes lumbar 
puncture, blood culture testing, immediate 
start of treatment with dexamethasone and 
intravenous antibiotics (combination 
therapy with ampicillin and third 
generation cephalosporin), and a search 
made for the focus of the infection (e.g., 
computed tomography or magnetic 
resonance tomography). 
    • Meningococcal septicemia 
    • Invasive infection 
All adverse events of special interest will be 
recorded and reported as SAEs, and 
subject narratives will be generated. 
Further information may be requested from 
the investigator. 
 
Assessment of Causality 
    • The investigator is obligated to 
assess the relationship between IMP and 
each occurrence of each adverse 
event/SAE. 
    • A “reasonable possibility” of a 
relationship conveys that there are facts, 
evidence, and/or arguments to suggest a 
causal relationship, rather than a 
relationship cannot be ruled out. 
    • The investigator will use clinical 
judgment to determine the relationship. 
    • Alternative causes, such as 
underlying disease(s), concomitant 
therapy, and other risk factors, as well as 
the temporal relationship of the event to 
IMP administration will be considered 
and investigated. 
    • The investigator will also consult the 
IB in his/her assessment. 
    • For each adverse event/SAE, the 
investigator must document in the 
medical notes that he/she has reviewed 
the adverse event/SAE and has provided 
an assessment of causality. 
    • There may be situations in which an 
SAE has occurred and the investigator 
has minimal information to include in 
Assessment of Causality 
    • The investigator is obligated to assess 
the relationship between IMP the adverse 
event/SAE. 
    • A “reasonable possibility” of a 
relationship conveys that there are facts, 
evidence, and/or arguments to suggest a 
causal relationship, rather than a 
relationship cannot be ruled out. 
    • The investigator will use clinical 
judgment to determine the relationship. 
    • Alternative causes, such as underlying 
disease(s), concomitant therapy, and other 
risk factors, as well as the temporal 
relationship of the event to IMP 
administration will be considered and 
investigated. 
    • The investigator will also consult the 
IB in his/her assessment. 
    • For each adverse event/SAE, the 
investigator must document in the medical 
notes that he/she has reviewed the adverse 
event/SAE and has provided an assessment 
of causality. 
 
 
 
 


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the initial report to, for example, a 
regulatory agency. However, it is very 
important that the investigator always 
makes an assessment of causality for 
every event before the initial 
transmission of the SAE data. 
    • The investigator may change his/her 
opinion of causality in light of follow up 
information and send a SAE follow up 
report with the updated causality 
assessment. 
    • The causality assessment is one of 
the criteria used when determining 
regulatory reporting requirements. 
The causal relationship of adverse events 
to administration of the IMP will be 
assessed according to the following 
criteria: 
    • Not related 
        ◦ Event or laboratory test 
abnormality with a time to 
administration of the IMP that makes a 
relationship impossible 
        ◦ Is most likely explained by 
concurrent disease or other drugs or 
chemicals (either pathophysiologically or 
clinically) 
        ◦ Has occurred before 
administration of the IMP in comparable 
severity and/or frequency 
 
 
    • Unlikely related 
        ◦ Event or laboratory test 
abnormality with a time to 
administration of the IMP that makes a 
relationship improbable (but not 
impossible) 
        ◦ Disease or other drugs provide 
plausible explanations 
 
 
 
 
 
 
 
 
 
 
 
 
    • Possibly related 
        ◦ Event or laboratory test 
abnormality with reasonable time 
relationship to administration of the IMP 
 
 
 
 
 
 
 
 
 
 
 
 
The causal relationship of adverse events to 
administration of the IMP will be assessed 
according to the following criteria: 
    • Not Related (must meet at least one 
criterion listed below) 
This category applies to events that are due 
to extraneous causes and are not timely 
related to the administration of the IMP if: 
        ◦ Event or laboratory test abnormality 
with a time to administration of the IMP 
that makes a relationship impossible 
        ◦ Is most likely explained by 
concurrent disease or other drugs or 
chemicals (either pathophysiologically or 
clinically) 
        ◦ Has occurred before administration 
of the IMP in comparable severity and/or 
frequency 
    • Unlikely Related (must meet at least 
first two criteria listed below) 
This category applies to events that are 
unlikely related to the administration of the 
IMP. The relationship of an event to the 
sIMP can be considered probably not 
related if: 
        ◦ The event does not follow a 
reasonable temporal sequence from 
administration of the drug 
       ◦ The event could readily have been a 
result of the patient’s clinical state or other 
underlying medical condition 
environmental or toxic factors, or other 
modes of therapy administered to the 
patient 
        ◦ The event does not follow a known 
response pattern to the suspected drug 
        ◦ The event does not reappear or 
worsen when the IMP is re-administered 
    • Possibly Related (must meet at least 
first two criteria listed below) 
This category applies to events that are 
unlikely to be related to the administration 
of the IMP, but the possibility cannot be 
ruled-out with certainty. The relationship 


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        ◦ Could also be explained by 
disease or other drugs 
        ◦ Information on IMP withdrawal 
may be lacking or unclear 
 
 
 
 
 
 
 
 
 
 
    • Probably related 
        ◦ Event or laboratory test 
abnormality with reasonable time 
relationship to administration of the IMP 
        ◦ Unlikely to be attributed to disease 
or other drugs 
        ◦ Response to withdrawal clinically 
reasonable 
        ◦ Rechallenge not required 
 
 
 
 
 
 
 
 
    • Certainly related 
        ◦ Event or laboratory test 
abnormality with plausible time 
relationship to administration of the IMP 
        ◦ Cannot be explained by disease or 
other drugs 
        ◦ Response to withdrawal plausible 
(pharmacologically or pathologically) 
        ◦ Event definitive 
pharmacologically or 
phenomenologically (i.e., an objective 
and specific medical disorder or a 
recognized pharmacological 
phenomenon) 
        ◦ Rechallenge satisfactory, if 
necessary 
of an event to the IMP can be considered 
possibly related if: 
       ◦ The event follows a reasonable 
temporal sequence from administration of 
the IMP 
       ◦ The event could readily have been a 
result of the patient’s clinical state, 
environmental or toxic factors, or other 
modes of therapy administered to the 
patient 
       ◦ The event follows a known response 
pattern to the suspected IMP 
    • Probably Related (must meet at least 
first three criteria listed below) 
This category applies to events that are 
considered with a high degree of certainty 
to be related to the administration of the 
IMP. The relationship of an event to the 
IMP drug can be considered probably 
related if: 
       ◦ The event follows a reasonable 
temporal sequence from administration of 
the IMP 
       ◦ The event could not be reasonably 
explained by the known characteristics of 
the patient’s clinical state, environmental 
or toxic factors, or other modes of therapy 
administered to the patient 
        ◦ The event disappears or decreases 
upon cessation of IMP or reduction in dose 
        ◦ The event follows a known response 
pattern to the suspected IMP 
    • Definitely Related (must meet at least 
first three criteria listed below) 
This category applies to events that are 
determined with certainty to be related to 
the administration of the IMP. The 
relationship of an event to the IMP can be 
considered definitely related if: 
        ◦ The event follows a reasonable 
temporal sequence from administration of 
the IMP or IMP levels have been 
established in body fluids or tissues 
        ◦ The event could not be reasonably 
explained by the known characteristics of 
the patient’s clinical state, environmental or 
toxic factors, or other modes of therapy 
administered to the patient 
        ◦ The event disappears or decreases 
upon cessation of IMP or reduction in dose 
and, if applicable, appears upon re-
challenge 
        ◦ The event follows a known response 
pattern to the suspected IMP 
        ◦ There are exceptions when an event 
does not disappear upon discontinuation of 


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the IMP, yet IMP relatedness clearly exists; 
e.g., 1) tardive dyskinesia, 2) fixed drug 
eruptions 
77 Contraceptive 
Guidance and 
Collections of 
Pregnancy Information 
Definitions 
1. Postmenopausal female: 
• A postmenopausal state is defined as no 
menses for 12 months without an 
alternative medical cause. 
• Females on HRT and whose 
menopausal status is in doubt will be 
required to use one of the non-hormonal 
highly effective contraception methods. 
Definitions 
Postmenopausal female: 
• A postmenopausal state is defined as no 
menses for 12 months without an 
alternative medical cause. 
Note: Females on HRT and whose 
menopausal status is in doubt will be 
required to use one of the non-hormonal 
highly effective contraception methods. 
77 Contraceptive 
Guidance and 
Collections of 
Pregnancy Information 
Contraception Guidance 
... 
Female subjects 
Female subjects of childbearing potential 
are eligible to participate if they agree to 
use a highly effective method of 
contraception consistently and correctly 
as described in Table 3. 
Contraception Guidance 
Male subjects 
Male subjects who have not had a 
vasectomy must, during the entire study 
participation and for at least one month 
after last administration of study drug: 
• either abstain from reproductive sexual 
intercourse or use a condom during 
intercourse 
• not donate sperm. 
Female subjects 
Female subjects of childbearing potential 
must not donate eggs and must agree to use 
a highly effective method of contraception 
consistently and correctly as described in 
Table 3. 
77 Contraceptive 
Guidance and 
Collections of 
Pregnancy Information 
Table 3 
Highly Effective 
Contraceptive Methods 
Table 3 
Highly Effective Contraceptive 
Methods 
Note: Subjects must have been on a stable 
dose of hormonal contraceptives for at 
least 4 weeks before Day 1. 
81 Prohibited 
biologics 
 
Note: Biologicals used for an underlying 
disease at a stable dose may be continued. 
 
 


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Appendix 8 
Amendment 02 
Rationale for Amendment 02 
Amendment 02 was enacted to: 
• Allow subjects with lesions on other parts of the body than the legs to enter the trial.  
Pyoderma Gangrenosum is a rare disease, and focusing on lesions of the lower 
extremity adversely limits the potential size of the subject population. 
• To allow the use of stable chronic opioid medication. Ulceration in the patients with 
Pyoderma Gangrenosum causes debilitating pain, and these patients are in need of 
strong pain relief. 
• Correct inconsistencies in the protocol. 
Corrections to spelling and punctuation are not listed. 


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List of changes 
Section 
Original text 
Amended text 
Protocol signatures 
Sponsor Signatory: 
Ronald Rosenburg, MD, PhD# 
... 
07745 Jena, Germany 
Ronald Rosenburg, MD, PhD# 
… 
07745 Jena, Germany 
telephone: 0049 89 414 189 7825 
Abbreviations and Definitions of 
Terms 
 
Q2W    Every 2 weeks 
10 Synopsis of Study 
Study Population Inclusion 
Criteria: 
5. In addition, the subject must 
fulfill at least 3 of the following 
6 criteria at screening: 
History of 
... 
Multiple ulcerations (at least 1 
occurring on the lower leg) 
Cribriform or “wrinkled paper” 
scar(s) at sites of healed ulcers 
5. In addition, the subject must 
fulfill at least 3 of the following 
6 criteria at screening: 
History of 
... 
Multiple ulcerations 
Cribriform or “wrinkled paper” 
scar(s) at sites of healed ulcers 
 
 
6. Subject has a minimum of 1 
evaluable ulcer (≥2 cm2) on the 
lower extremity at screening 
6. Subject has a minimum of 1 
evaluable ulcer (≥2 cm2) at 
screening 
Study Population Exclusion 
Criteria: 
Evidence of active tuberculosis 
Evidence of active  or latent 
tuberculosis 
 
9. An ankle brachial index of less 
than 0.8 or toe pressure of less 
than 80 mmHg in subjects with a 
compromised vascular system 
(e.g., diabetic subjects) within 
previous year or at screening 
9. Subjects with Ulceration due to 
medical causes other than 
pyoderma gangrenosum  (e.g. 
diabetic ulceration) 
 
17. Known hypersensitivity to any 
excipient of the IMP 
17. Known hypersensitivity to 
polysorbate 80 (excipient of the 
IMP) 
19 Schedule of Assessments 
[deleted measurement of “Ankle 
brachial index/toe pressure”] 
 
 
 
[Added footnote  “b” to chest X-
ray] 
[Footnotes] 
a Only if wound still open 
b Subjects with a compromised 
vascular system (e.g., diabetic 
subjects), within previous year or 
at screening 
c This photograph is the 
Baseline for subsequent 
Physician’s Global Assessments 
d Only for subjects in Group 1 
and Group 2 
a Only if wound still open 
b An historical X ray may be 
used if taken within 6 months 
prior to screening 
c This photograph is the 
Baseline for subsequent 
Physician’s Global Assessments 
d Only for subjects in Group 1 
and Group 2 
27 Overall Design 
Screening Day 14 
Screening Day -7 to Day -35 
[Initial dose] 
800 mg 
Q2W 
(3 doses) 
800 mg 
(3 doses) 
34 Recording of prior and 
concomitant therapy and 
procedures 
Any medication or vaccine 
(including procures such as laser- 
or photo-therapy, over-the-counter 
or prescription medicines, 
vitamins, and/or herbal 
supplements) that the subject has 
Any medication or vaccine 
(including procures such as laser- 
or photo-therapy, over-the-counter 
or prescription medicines, 
vitamins, and/or herbal 
supplements) that the subject has 


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used in the 3 months81 before 
screening, is receiving at the time 
of screening, or receives during 
the study must be recorded in the 
source data and CRF along with 
used in the 3 months, or 
biologicals (see 81 for Prohibited 
Biologics) used within 12 months, 
before screening, is receiving at 
the time of screening, or receives 
during the study must be recorded 
in the source data and CRF along 
with 
35 Allowed Concomitant Therapy 
Analgesic therapy for pyoderma 
gangrenosum 
 
Analgesic therapy may be initiated 
at any time during the study with 
non opioid analgesic if a subject’s 
pain worsens after Day 1. All non
opioid analgesics (including 
tramadol) are allowed at the 
recommended or prescribed dose. 
Analgesic therapy for pyoderma 
gangrenosum 
 
Short-acting opioid or non-opioid 
analgesic therapy may be initiated 
at any time during the study. If 
possible, analgesic therapy should 
be avoided on the day of pain 
assessments until the assessments 
are made. 
35 Prohibited Therapy 
The following therapies are 
prohibited for all subjects from 
screening until Visit EOT or 
discontinuation from the study: 
... 
oral opioid analgesics 
The following therapies are 
prohibited for all subjects from 
screening until Visit EOT or 
discontinuation from the study: 
... 
Non-stable, chronic use of high 
dose oral opioid analgesics 
38 Screening 
The following procedures will be 
conducted and documented at the 
Screening visit: 
... 
• Record vital signs 
• Measure ankle brachial index/toe 
pressure in subjects with a 
compromized cardiovascular 
system (unless performed in the 
previous year) 
• Record a 12 lead ECG 
• Chest X-ray 
• Take photograph of target ulcer 
for area and volume 
measurements 
The following procedures will be 
conducted and documented at the 
Screening visit: 
… 
• Record vital signs 
• 
• Record a 12 lead ECG 
• Perform a chest X-ray. An 
historical X-ray can be used if 
taken within 6 months prior to 
screening 
• Take photograph of target ulcer 
for area and volume 
measurements 
50 Chest X-ray 
[moved from section 9.4.8] 
A standard chest X-ray will be 
performed at screening to exclude 
active tuberculosis. 
A standard chest X-ray will be 
performed at screening to exclude  
tuberculosis. An historical X-ray 
can be used if taken within 6 
months prior to screening. 
54 Blood Sampling Volumes 
… 
Repeat or unscheduled samples 
may be taken for safety reasons or 
for technical issues with the 
samples. 
 
… 
Repeat or unscheduled samples 
may be taken for safety reasons or 
for technical issues with the 
samples. 
If values are out of range during 
screening, a single retest is 
allowed. 
 

ICF_003.pdf: 
InflaRx 
IFX-1-P.2.7 
Informed Consent Form 
Version 7.0, 14 May 2020 
Page 1 of 23 
 
SUBJECT INFORMATION & INFORMED CONSENT FORM 
Study Title:  
Open label exploratory phase IIa trial to investigate the safety and efficacy 
of IFX-1 in treating Subjects with Pyoderma Gangrenosum (OPTIMA) 
Short Title:  
Exploratory study of IFX-1 in Pyoderma Gangrenosum 
Study No.:  
IFX-1-P.2.7 
Sponsor:  
InflaRx, Winzerlaer Strasse 2, 07745 Jena, Germany 
Investigator:  
Dr. Afsaneh Alavi 
Address:  
 
 
Telephone Number:  
 
 
INTRODUCTION 
You are invited to participate in a drug research study for pyoderma gangrenosum. Participation in 
this study is voluntary (your choice). If you join this study, you can stop at any time. You have the 
right not to sign this consent form. If you do not sign, you cannot take part in this research study. If 
you decide to participate, you will be asked to sign and date at the end of this form. 
Please read the following information carefully. It contains important information to help you 
decide whether to participate in this research study. The study staff will have a detailed interview 
with you to inform you about the study and the possible benefits and risks of your participation. 
Ask questions about anything that is not clear at any time.  
You may take home an unsigned copy of this information to think about and discuss with your 
family, friends or family doctor before you make your decision to participate or not. 
For your information, this study is being paid for by InflaRx and the study doctor is paid by the 
sponsor to conduct this study. 
 


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WHAT IS A RESEARCH STUDY? 
A research study is an experiment whose purpose is to answer specific questions, such as: 
• Does this drug work? Is it safe? 
• What kind of treatment is better? 
Being in this study does not replace your regular medical care. 
WHY HAVE YOU BEEN INVITED TO TAKE PART IN THIS STUDY? 
You have been invited to take part in this study because you have been diagnosed with an ulcerative 
form of pyoderma gangrenosum. 
Pyoderma gangrenosum is a rare skin condition that causes painful ulcers (open sores). It is usually 
treatable but could take some time to heal and may leave some scarring. Pyoderma gangrenosum 
usually appears suddenly as either a small pimple, red bump or blood blister. The reaction may 
sometimes be triggered by minor skin damage or an injury – for example, it may develop around a 
wound, a needle prick, or an insect bite. 
The skin then breaks down into a painful ulcer with a purple or blue edge that may ooze fluid. The 
ulcer can grow quickly and several ulcers may develop in the area. If the ulcer gets infected, 
patients also feel unwell and develop a high temperature (fever). Pyoderma gangrenosum usually 
occurs on the legs, although it can affect any area of skin. It sometimes develops around an injury or 
surgical wound. 
The exact cause of pyoderma gangrenosum is not understood, but it's thought to be a reaction to a 
disease or illness. However, many people have no related condition and there is no obvious reason 
for it. 
When the affected skin tissue is tested, it usually has a high concentration of neutrophils (white 
blood cells), which are a sign of inflammation. In pyoderma gangrenosum, the body appears to have 
an overactive inflammatory system. This means pyoderma gangrenosum may be related to over 
activity of the immune system. 
WHAT MEDICATION IS BEING TESTED? 
IFX-1 is an antibody that is being developed for the treatment of various diseases in which an 
overactive inflammatory system plays a role. It blocks certain pathways in the activation of 
inflammation. This treatment is administered via intravenous infusions. 
IFX-1 has not been approved as a treatment for any disease in any country and it is not available to 
people who are not participating in research studies like this one. Thus, its use in this research study 
is considered experimental. 


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WHAT IS THE PURPOSE OF THE STUDY? 
The overall purpose of this study is to assess the safety, tolerability and effectiveness of different 
doses of IFX-1 in subjects with the ulcerative form of pyoderma gangrenosum over an extended 
period of time. 
In addition, this study will investigate some additional scientific measures that may give an insight 
into how the drug is working. 
The study will also investigate antibodies produced by your body in response to the study drug and 
their effect on its effectiveness and safety. 
HOW MANY PATIENTS WILL TAKE PART IN THE STUDY? 
This study is being conducted in a few research centers in Canada (and potentially the USA) and is 
expected to enroll approximately 18 subjects. 
HOW LONG WILL YOU BE IN THE STUDY? 
If you decide to participate in this study, your participation in this study is anticipated to be 
approximately 9 months. 
The study will consist of a visit for screening, then about  to  weeks later you will be started on 
the intravenous infusions of IFX-1. You need to return 
 times at 
 days, and then every 
2 weeks for further infusions. At the end of the study, there will be 2 further visits after 30 days and 
60 days to see how you are getting on. 
WHAT WILL HAPPEN DURING THE STUDY? 
If you decide to take part in this study, you will be asked to sign this informed consent form before 
any study-related procedures are performed. A flow chart summarizing the study procedures can be 
found at the end of this section. 
An overview of what is done at each study visit is given below. 
Screening Visit (Visit is expected to take approximately 3 hours) 
The screening visit will be performed to see if you are suitable for the study. If you agree to be in 
this study, the following tests and evaluations will be performed at this visit. Depending on when 
your last visit to the doctor was, you may not need to have all of the following procedures 
performed: 
• Review criteria to see if you qualify. 
• Demographics – your date of birth, gender, race, ethnicity, and disease status. 


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• Review of your health and all medications (including prescription, over the counter, and 
herbal remedies) you are currently taking. 
• Complete physical examination including measurement of vital signs (blood pressure, pulse 
rate, breathing rate and body temperature). 
• Your weight will be measured. 
• An ECG (electrocardiogram), a test of the electrical activity of your heart will be performed. 
• A chest X-ray will be performed (unless a recent one is available) to see if you have any 
problems with you lungs such as tuberculosis. 
• A test for tuberculosis will be performed to check to see if you have tuberculosis. 
• Blood and urine samples will be collected for safety laboratory testing (i.e, liver or kidney 
function).  
• If you are a woman who can have a child, a pregnancy test on a blood sample will be 
performed. Results of the pregnancy test must be negative for you to participate in this 
study. 
• Blood samples will be also taken to check if you have AIDS or hepatitis. A positive HIV or 
Hepatitis test result will be reported to health authorities as required by local law and you 
may be referred to public health for counseling. 
• The severity of your pyoderma gangrenosum will be evaluated visually by the study doctor 
using different clinical assessments. 
• A digital colour photograph of one of your ulcers will be taken. Any identifying features 
will be blurred or covered, your face will not be shown and people who see the photographs 
will not be able to recognise you. The purpose of the photograph is to show your pyoderma 
gangrenosum before and after the trial treatment, and how it may be changing during the 
trial.  
• You will be asked to complete a questionnaire about your overall health and quality of life. 
• The ulcer will be dressed using a standard dressing and compression. 
 
Visit V1 (Visit is expected to take approximately 3 hours) 
At visit V1 it will be confirmed that you are suitable for the study. The following tests and 
evaluations will be performed at Visit V1: 
• If there are any updates or new information for your medical history, this information will 
be collected.  
• Review of your health and all medications you are currently taking. 
• You will be asked to complete a questionnaire about your overall health and quality of life. 
• Complete physical examination including measurement of vital signs (blood pressure, pulse 
rate, breathing rate and body temperature). 


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• Your weight will be measured. 
• An ECG will be performed. 
• As applicable, a urine pregnancy test will be performed. 
• A stool sample will be given for scientific evaluation. 
• You will be questioned about any changes to your health and side-effects (adverse events) 
that might have occurred since the last visit. 
• The photograph of the ulcer will be repeated. 
• A small sample of tissue will be cut from your ulcer (biopsy). The biopsy site will first be 
carefully cleaned and disinfected. A local anaesthetic will then be injected just under your 
skin, using a thin needle, so that you will not feel any pain during the biopsy procedure. The 
injection may cause a burning and painful feeling for a few seconds. The biopsy will then be 
taken using a 4.5 mm hollow needle (biopsy punch). Some bleeding is to be expected. The 
wound will be closed with a single stitch, if necessary, and bandaged. If a stitch is used, it 
will be removed at your next trial visit. When the wound is completely healed, only a thin 
scar, maximum 2 mm long, is likely to visible on the skin.  
The purpose of the skin biopsy is to assess and describe the pyoderma gangrenosum of your 
lesions.  
• A stool sample will be collected to look at various aspects of the inflammatory process.  
• If your ulcer is draining fluid, some fluid will be collected from your ulcer to look at various 
aspects of the inflammatory process. 
• The ulcer (open sore) will be dressed using a standard dressing and compression. 
• Blood samples will be also taken to look at various aspects of the inflammatory process, to 
see if your body is producing antibodies against IFX-1. 
• The first dose of IFX-1 will be given into a vein over 30 to 60 minutes. 
• You will be observed for about 30 minutes following the infusion for any reaction to the 
study drug. 
 
Treatment Period (Visit V2 to Visit V15 and End of Treatment (EOT) Visit) 
(Visits expected to take approximately up to 3 hours) 
The following tests and evaluations will be performed at each of the above planned study visits 
during the treatment period: 
• Review of your health and all medications you are currently taking. 
• Measurement of vital signs. 
• Assessments of the ulcer will be made. 
• A photograph of the ulcer will be taken. 


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• You will be questioned about any changes in your health or side-effects (adverse events) 
that might have occurred since the last visit. 
• The ulcer will be dressed using a standard dressing and compression. 
• IFX-1 will be given into a vein over 30 to 60 minutes (except for Visit EOT).  
• At Visit V2 you will be observed for about 30 minutes following the infusion for any 
reaction to the study drug. 
• Pregnancy tests (either urine or blood) will be performed every 4 weeks. 
At Visits V4, V6, V10, and EOT the following tests and evaluations will also be performed: 
• You will be asked to complete a questionnaire about your overall health and quality of life. 
• If your ulcer is draining fluid, some fluid will be collected from your ulcer for scientific 
evaluations. 
• Blood and urine samples will be collected for safety laboratory testing (side-effects that can 
be tested in your blood/urine). 
• Blood will be taken to measure the concentration of IFX-1. 
• Blood samples will be also taken for scientific evaluations. 
• A stool sample will be given for scientific evaluation. 
At Visit V10 and EOT the following tests and evaluations will also be performed: 
• Complete physical examination including measurement of vital signs (blood pressure, pulse 
rate, breathing rate and body temperature). 
• Your weight will be measured. 
At Visit EOT the following evaluation will also be performed: 
• ECG (electrocardiogram). 
At Visit V7, the dose of IFX-1 may be increased by the investigator. 
Follow-Up Period (Visits expected to take approximately 1 – 2 hours) 
You will also return to the study clinic 30 days and 60 days after the last dose of study medication 
for the 2 observation visits. These will be your last visits. 
The following procedures (see flow chart) will be performed during the follow-up period: 
• Review of your health and all medications you are currently taking. 
• You will be asked to complete a questionnaire about your overall health and quality of life. 
• Complete physical examination including measurement of vital signs (blood pressure, pulse 
rate, breathing rate and body temperature). 


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• Your weight will be measured. 
• Assessments of the ulcer will be made. 
• A photograph of the ulcer will be taken. 
• Pregnancy test (either urine or blood). 
• Blood and urine samples will be collected for safety laboratory testing. 
• Blood will be taken to measure the concentration of IFX-1. 
• Blood samples will be also taken for scientific evaluations. 
• The ulcer will be dressed using a standard dressing and compression. 
• You will be questioned about any changes to your health or side-effects (adverse events) 
that might have occurred since the last visit.


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STUDY FLOW CHART 
Visit 
Screening 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
EOT 
Ob1 
Ob2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Body weight 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Quality of life questionnaire 
X 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Pyoderma gangrenosum 
assessments 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Photograph of ulcer 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ulcer biopsy 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Collection of ulcer fluid 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
12 lead ECG 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Chest X-ray 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety laboratory blood tests 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
X 
HIV and hepatitis serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tuberculosis test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
IFX-1 concentrations 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Immunology Blood 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
X 
Urinalysis 
X 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
X 
Stool sample 
 
X 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Tolerability and adverse event 
assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Standard dressing and 
compression therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
IFX-1 administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Possible dose increase 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 


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Unscheduled visits 
At any time during the study, your study doctor may ask you to attend the study clinic to repeat any 
of the above tests if he/she feels it is necessary for your safety and well-being. In some cases, it may 
be necessary to take additional blood samples (e.g., for safety tests). If this occurs, the total blood 
volume taken may be increased. 
How much blood will be taken from you during the study? 
The total amount of blood taken from you will not exceed 
mL (about 
tablespoons). This is 
about half of the amount of blood taken if you donate blood. The maximum at any single visit will 
be 75 mL (about 5 tablespoons). 
WHAT HAPPENS IF YOU STOP THE STUDY EARLY? 
If you stop taking the study medication early and you cannot or will not continue in the study, you 
will be asked to return for an End of Treatment (EOT) visit. If you decide to stop the study during a 
planned study visit, you will have the End of Treatment (EOT) visit instead of your planned visit. 
You will have the applicable procedures listed above for the Follow-up Period performed for your 
EOT visit. 
WHAT WILL YOU HAVE TO DO?  
In order for this study to provide good information about how the study drug works in subjects with 
your condition, you will be expected to do the following: 
• Attend all study visits and have any assessments scheduled (as documented above). Missing 
scheduled study visits and/or injections may lead to invalid research data and you may be 
discontinued from the study and unable to receive any more treatments. 
• Tell the study doctor if you experience any side effects or any health problems, even if you 
do not know if it is related to the study. 
• Tell the study doctor about any therapies you are currently taking, including over the 
counter medications, herbal or alternative remedies, and if you have any changes in or start 
any new medications. Any drug interactions need to be documented. 
• Follow the directions of the study doctor and study team, including use of appropriate birth 
control. 
• If you are a woman of childbearing potential you must agree to use highly effective methods 
of contraception as discussed with your study doctor. 
• If you are a man and you have a female partner who is able to have children, you must 
accept to use contraception (condom), as discussed with your study doctor.  
• Carry your subject card with you as long as you are in the study and show it to any medical 
staff that may be involved in your healthcare. 


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• Refrain from participating in other research studies while you are in this study. 
• Tell the study doctor or study team if you wish to stop being in the study. 
WHAT ARE THE POSSIBLE ADVANTAGES/BENEFITS, AND POSSIBLE 
DISADVANTAGES, RISKS OR DISCOMFORTS OF TAKING PART IN 
THIS STUDY? 
You may or may not receive a direct health benefit from participating in this study. It is possible 
that the symptoms of your condition will not improve during the study or may even worsen. 
The ability of IFX-1 to treat your pyoderma gangrenosum ulcers has not yet been demonstrated. It 
is important for you to understand that your condition may improve, remain the same, or worsen. 
Treatment with this study drug may also involve risks to your future health that we currently don’t 
know about. 
Participating in a clinical research study involves some unforeseeable risks of side effects that could 
occur.  
You will have the opportunity to discuss any questions you might have about the severity and 
frequency of risks and other potential discomforts. In addition to the side effects listed, there is 
always the risk of developing side effects which are not known at this time. 
If you are not sure what the side effects described below are, ask your study doctor to explain them 
to you. 
If you suffer any of these side effects (or any others not listed) or you think you are experiencing a 
side effect, during this study, please tell your study doctor immediately (see ‘Who should I contact 
for more information?’).  
You will be monitored carefully to check for these risks. Your study participation may be stopped if 
any signs that the drug is harmful to you or other damage occurs. You need to tell your study doctor 
or a member of the study team immediately if you experience any side effects. 
Any side effects or other health issues occurring during the study will be followed up by the study 
doctor. 
The information we get from this study may help improve the treatment of people with the same 
condition in the future. 
Study Drug Risks: 
As of 01 November 2019, approximately
 people (
 healthy adults and 
 patients) have 
received IFX-1 in 5 other research studies. Based on the study data available, IFX-1 was well 


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tolerated when administered to healthy subjects and patients with hidradenitis suppurativa (also 
known as acne inversa) or other conditions. 
 
Taking the study drug in this study may cause you to have one or more of the side effects as listed 
below.  
The following side effects were reported as possibly related to IFX-1: 
Common (may affect up to 1 in 10 people):  
• impaired healing,  
• headache. 
Uncommon (may affect up to 1 in 100 people):  
• leukocytosis (high level of white blood cells),  
• atrial fibrillation (rapid and irregular heart beating),  
• nausea,  
• acute (severe and sudden) liver failure,  
• liver damage,  
• nasopharyngitis (common cold),  
• C-reactive protein (unspecific inflammatory blood marker) level increased,  
• blood pressure decreased,  
• heart rate decreased,  
• pulmonary embolism (blockade of a lung artery by a blood clot),  
• hypertension (high blood pressure).  
Risks related to how IFX-1 works:  
The potential risks associated with IV administration of IFX-1 due to how it works include the 
following: 
• There is a theoretical risk of an increased rate of infections with IFX-1. Current data do not 
suggest that subjects treated with IFX-1 are at significantly increased risk of infection, but it 
could happen.  
• Meningitis can rapidly become life-threatening or fatal especially if not recognized and treated 
early. It happens when the lining that covers the brain and spinal cord (called the "meninges") 
gets inflamed or infected. If you experience any of the following symptoms, you should 
immediately call your study doctor. If you cannot reach your study doctor, go to an emergency 
department immediately: 


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Fever (but some people have a temperature that is lower than normal instead of a fever); 
headache; stiff neck; nausea or vomiting; acting confused, or being hard to wake up; having 
light bother a person's eyes; a rash that looks like red or purple spots on the skin that do not go 
away when touched; seizures (waves of abnormal electrical activity in the brain. They can make 
people pass out, or move or behave strangely). 
• Development of anti-drug antibodies may result in lack of effectiveness or could lead to allergic 
reactions. 
• Hypersensitivity (allergic) / Anaphylactic reactions: Because IFX-1 is an antibody/protein, a 
general risk for allergic reactions exists. An allergic reaction may cause symptoms such as rash, 
difficulty breathing, drop in blood pressure and if severe (called anaphylactic reaction), could be 
life threatening. Administration of IFX-1 in clinical Phase I and II studies has been associated 
with a low frequency of infusion-related reactions. 
• Since IFX-1 works, in part, in the same way to an already approved medicine, eculizumab, 
some known side effects of eculizumab could also occur during treatment with IFX-1. These 
side effects include: leukopenia (decreased level of white blood cells), thrombocytopenia 
(decreased level of platelets in blood), anaphylactic reactions, diarrhea, vomiting, swelling, 
infusion-related reactions, chest discomfort, fever, and chills.  
Allergic Reactions: 
All drugs have a potential risk of an allergic reaction. Allergic reactions may vary from mild (rash, 
hives, itching) to severe reactions such as anaphylaxis (which may include difficulty breathing, 
swelling of the face or throat, low blood pressure, or loss of consciousness). A severe allergic 
reaction requires immediate medical treatment and could result in permanent disability or death. It 
is important to tell your study doctor about any past allergic reactions that you may have had to 
other drugs including antibody drugs (which are usually given by IV or injection under the skin).  
If you seek medical care for a possible severe allergic reaction, please request the treating health 
care provider to contact the study physician. 
Overdose 
The consequences of an overdose with IFX-1 are not known 
Infusion of study drug 
It is possible that you may have an infusion-related reaction (e.g. local pain, swelling, reddening). 
Blood Sampling 
Blood draws may cause pain, bleeding, and/or bruising at the puncture site. Furthermore, there is a 
small risk of light-headedness and/or fainting. In rare cases, the puncture site can also become 
infected or nerves may be damaged, inducing long-lasting abnormal sensations (paresthesia), 
impaired sensation of touch and persistent pain. Frequent blood collection may cause anemia (low 
red blood cell count), which may create a need for blood transfusions. 


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Electrocardiogram (ECG) 
Skin irritation is rare but could occur during an ECG from the electrodes or gel that is used. To do 
the ECG, you will have pads placed on different parts of your chest. There is no pain or discomfort 
during an ECG; however, removing the pads may cause some irritation to your skin. 
Ulcer biopsies 
The injection of the local anaesthetic may cause a burning and a painful feeling for a few seconds. 
Some bleeding is to be expected. The biopsy may be painful.  
Questions/Questionnaires 
Answering the study doctor or study staff’s questions and filling out questionnaires could lead you 
to feel uncomfortable or upset. Please tell the study doctor or study staff if you feel uncomfortable 
or upset at any time during your study visit. You have the right to refuse to answer any questions. 
Blood pressure test (a measure of the pressure in your arteries as the heart pumps)  
The squeezing of an inflated blood pressure cuff on your arm may be uncomfortable. It usually 
takes only a few seconds.  
Women of childbearing potential 
Currently we are not fully aware of the effects of the study drug on unborn babies, or pregnant or 
breastfeeding women. If you are pregnant, or may become pregnant, treatment with the study drug 
may lead to new, previously unknown, side effects that we currently don’t know about and this may 
involve risks to you or your unborn baby. Because of this, women who can have children must have 
a negative pregnancy test at the start of the study. A serum or urine pregnancy test will be 
performed approximately monthly during the study. 
If your partner is not sterilized (i.e. vasectomy), you must agree to use a highly effective method of 
contraception such as combined (estrogen and progesterone containing) hormonal contraception 
during the entire study participation and for at least one month after last administration of study 
drug. 
Highly effective birth control includes:  
• oral contraceptive pill (estrogen and progestogen containing or progestogen only) 
• combined (estrogen and progestogen containing) vaginal hormone ring 
• combined (estrogen and progestogen containing) hormone contraceptive transdermal patch  
• progestogen only hormonal injections 
• progestogen contraceptive implant in combination with intrauterine device (IUD), 
intrauterine hormone-releasing system (IUS) or bilateral tubal occlusion 


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A vasectomized partner is a highly effective contraception method provided that the partner is the 
sole male sexual partner of the woman of child-bearing potential and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used. 
Sexual abstinence is accepted as highly effective method of contraception only if defined as 
refraining from heterosexual intercourse during the entire study participation and for at least one 
month after last administration of study drug, and if it is your preferred and usual lifestyle.  
If you become pregnant during the study or within 1 month of you stopping the study drug or 
treatment, you should immediately tell the study doctor. You will be asked by the study doctor to 
monitor your pregnancy throughout, and until conclusion. Information will be collected if you give 
permission. 
If you are currently breastfeeding, you cannot participate in the study. 
As a precaution, please do not donate eggs during the entire study participation and for at least one 
month after last administration of study drug.  
Men of childbearing potential 
We do not know if taking the study drug will affect sperm. As a result, men who have not had a 
vasectomy must either (a) abstain from reproductive sexual intercourse or (b) use a condom during 
intercourse. These precautions should be taken during the entire study participation and for at least 
one month after last administration of study drug. 
As a precaution, please do not donate sperm during the entire study participation and for at least one 
month after last administration of study drug. 
WHAT HAPPENS IF YOU DO NOT TAKE PART IN THE STUDY? 
Your participation in this study is voluntary. You do not have to be in this clinical study to receive 
treatment. If you choose not to participate in this study, there will be no negative consequences for 
the healthcare you receive, and your access to regular medical care will not be affected. 
WHAT ALTERNATIVE TREATMENTS ARE AVAILABLE? 
Most people with pyoderma gangrenosum need to take steroids, either applied to the ulcer or by 
mouth. Some people need to take immunosuppressants. for other conditions (an immunosuppressant 
is any drug or substance that suppresses the immune response). As pyoderma gangrenosum is 
thought to be caused by an overactive immune system, these may be able to reduce pain and help 
the ulcers to heal. 
Your doctor can provide you with medical treatments for pyoderma gangrenosum, which includes, 
but is not limited to:  


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• Corticosteroids. These drugs may be applied to the skin, injected into the wound or taken by 
mouth (prednisone). Using corticosteroids for a long time or in high doses may cause 
serious side effects. Because of this your doctor may prescribe steroid-sparing (nonsteroidal) 
drugs if you need long-term treatment. 
• Steroid-sparing drugs. An effective nonsteroidal drug is cyclosporine. Other options include 
mycophenolate (Cellcept), immunoglobulins, dapsone, infliximab (Remicade) and 
tacrolimus (Protopic), which is a calcineurin inhibitor. Depending on the type of drug used, 
it may be applied to the wounds, injected or taken by mouth. 
• Pain medication. Depending on the extent of your wounds, you may benefit from pain 
medication, especially when dressings are being changed.  
• In addition to applying medicine directly to your wounds, your doctor or wound care 
specialist will cover them with a non-sticky, moist (not wet or dry) dressing and, perhaps, an 
elasticized wrap. You may be asked to keep the affected area elevated. 
Each of these alternative treatments have some benefits and some risks. Please talk to the study 
doctor about your options before you decide whether you will take part in this study. The study 
doctor will further discuss with you the risks and benefits of the alternative treatments. 
WHAT IF NEW INFORMATION ABOUT THE STUDY BECOMES 
AVAILABLE? 
Sometimes new information about the study is received. You will be told if any relevant new 
information becomes available that may affect your willingness to carry on taking part in the study. 
If this happens, your study doctor will contact you as soon as possible, and will discuss whether you 
should continue in the study. If you decide not to carry on, your study doctor will make 
arrangements for your care to continue. If you decide to continue in the study you may be asked to 
sign a new consent form. 
Also, if new information becomes available, your study doctor may stop your participation without 
your consent. If this happens the reasons will be explained and arrangements made for your care to 
continue. 
WILL YOU BE PAID FOR TAKING PART IN THIS STUDY? 
There will be no cost to you for taking part in this study. You will be provided with all study drugs, 
examinations and medical care related to the study at no cost to you.  
 
Reimbursement for travel is also possible. 
This will be paid upon study completion or discontinuation or per visit, whichever you choose. 
Your study doctor will explain this in more detail, including the method and frequency of 
reimbursement payments. 
COMPENSATION FOR RESEARCH RELATED INJURIES 
You may experience bad or harmful reactions or other injuries resulting from the study drug or a 
study procedure. The Sponsor will pay for the cost of medical treatment for any injury that is due to 


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treatment with the study drug or study procedure (that has been used as described in the study 
protocol) that are not covered by the public health care system. 
Any compensation payable for any injury caused to you by taking part in this study will be in line 
with local guidelines. The Sponsor will not compensate you where the injury has happened because 
a procedure has been carried out that is not in line with the study protocol or where the study doctor 
has not acted with the care or skill that is expected. .   
The Sponsor has taken out an insurance policy to cover compensation for any personal injury 
resulting from your taking the study drug, provided such personal injury is not due to fault or 
carelessness of the study doctor or his team. 
If you have medical insurance please check with your insurance company that taking part in this 
study will not affect your policy. 
You will not lose any of your legal rights or release the sponsor, the study doctor, or the research 
team from liability for mistakes or intentional misconduct by signing this consent document. 
If you are injured during this study, your study doctor will discuss with you the available medical 
treatment options. 
WILL YOUR TAKING PART IN THIS STUDY BE KEPT CONFIDENTIAL 
AND HOW WILL YOUR PERSONAL INFORMATION BE USED? 
This confidentiality section describes your rights and explains how your personal health information 
will be collected, used, and disclosed. 
To help answer the research questions, the study doctor and research team will collect certain 
personal health information about you from your original medical records and any data resulting 
from your participation in this study. Your personal health information will be collected, used and 
shared with others as explained in this section. If you don’t give this permission, you will not be 
able to participate in the study. 
The following are examples of personal health information that may be collected: 
• your name, address, telephone number, date of birth, medical record numbers and/or other 
identifying information. 
• results of tests and procedures such as physical examination details, as well as the results of 
any blood testing, x-rays, other medical procedures or tissue sample testing. 
• your biological samples. 
• information about your medical conditions and history including dates relating to various 
medical procedures.  
• photographs of your ulcers. You will not be able to be identified by these photographs as 
only the affected skin will be photographed. Tattoos or other identified marks will be 


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removed in photos to protect your identity. The photographs may be additionally used for 
the following purposes: 
- as part of scientific presentations to other researchers. 
- to be published in scientific books or journals. 
- as part of training materials for training and education purposes. 
If anyone uses the photographs in scientific meetings, journals, books or similar, or for 
training purposes, you will not be paid. The sponsor will own the rights to the photographs. 
Your identity will be protected to the extent possible, and your name will never be used if 
the photographs are published or shared with researchers or the general public. Please ask 
the trial staff if you would like to know more about how your information will be protected 
while you are participating in this trial. 
 
By signing this document, you are allowing InflaRx and anyone working on its behalf, the study 
doctor and his/her representatives, the research team, Research Review Board Inc. (the ethics 
committee that reviewed the ethical aspects of this study), and organizations that regulate research 
in Canada or other countries (such as the Food and Drug Administration [FDA] and the Health 
Products and Food Branch of Health Canada) to have access to your identifiable personal health 
information at the study site to verify that the data is correct and check that the study is being 
conducted properly. 
Your study records, biological samples and accompanying data will receive a unique code in place 
of information that can be used to identify you (such as your name or address). 
The sponsor will not be able to link the assigned code number with your identity. 
Your coded study records, samples and accompanying data will be transferred, stored and processed 
by the sponsor and anyone working on its behalf and the people and companies that it works with 
on the study, the ethics committee and/or organizations that regulate research. These organizations 
may be located outside of Canada, such as the United States, where data protection requirements 
may be less restrictive than in Canada. Once such coded information is transferred outside of 
Canada, it will be subject to the laws of that country where it is stored. That country may have laws 
that require that such coded information be disclosed to the government under different 
circumstances than would your country of residence. 
Recognizing that your privacy is important to you, the study doctor, the sponsor and anyone 
working on their behalf employs technical security measures to protect your personal information. 
The study doctor, the sponsor and anyone working on their behalf will take all reasonable steps to 
keep secure any personal information they hold about you against loss or theft, as well as 
unauthorized access, use, copying, modification, disclosure or disposal, and to keep this information 
accurate and up to date. Your study records, including confidential information about you collected 
during the study will be kept in a secure location. 


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After this study has been completed, it is possible that your coded health information may be used 
by the sponsor and/or people or companies working with the sponsor for further research relating to 
the study drug, your disease or similar diseases and medical conditions. 
Your personal health information will be kept as confidential as possible. If the results of the study 
are used or published in a study report or scientific presentation, your identity will remain 
confidential. By signing this informed consent form, you give permission for the collection, use and 
disclosure of your personal health information as described in this form or as permitted by law.  
Access to your personal health information begins as soon as you sign this form. Your personal 
health information will be kept for a minimum of 25 years, as required by Canadian law. 
You have the right to see and get a copy of your study records, subject to certain exceptions 
prescribed by law. However, by signing this informed consent, you agree that you may not get to 
see your records until after the study is over if this would impact the integrity of the study.  
With your permission, your primary care physician/family physician/other physicians may be 
informed if you agree to be in this study. If you grant permission the study doctor may contact your 
other physicians to obtain medical records. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time.  
WHAT WILL HAPPEN TO ANY SAMPLES YOU GIVE? 
As part of this study we are obtaining blood samples from you. They will be sent to central 
laboratories for analysis. They will only be used for tests and exams listed in this consent form. 
Additional blood samples collected for Anti-Drug Antibodies and for Biomarkers assessments will 
also be stored for possible future analysis for up to 20 years after the end of the study at InflaRx 
GmbH in Germany.  These will include analyses directly related to this study.  
Biomarkers are naturally occurring substances in the body which may affect how a disease responds 
to the study drug. Your blood samples may be analyzed for different types of biomarkers: proteins, 
peptides (pieces of proteins), or other types of factors like lipids (fat molecules) that could help 
predict how Pyoderma Gangrenosum disease develops or help understand why the disease may be 
more severe and how it responds to IFX-1. They may also be used for the development of 
diagnostic tests related to IFX-1.  
To protect your privacy, your samples will be labeled only with your study number and will be 
stored securely and confidentially. No genetic testing will be performed on your samples.  


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WHAT HAPPENS IF INFLARX WANTS TO PERFORM OTHER TESTS ON 
YOUR BLOOD SAMPLES AT A LATER TIME? 
Your permission will be required for carrying out any new analysis on the samples not connected to 
this study – you will be asked to agree in this consent form to allow further use of the samples. You 
have the right to refuse. This refusal will not stop your taking part in this study. 
These blood samples will be stored for possible future analysis for up to 20 years after the end of 
the study at a suitable storage facility. 
You can withdraw your consent for your samples to be used for future analyses. In this case your 
samples will be destroyed only after they are no longer needed for the main study. You would need 
to tell your study doctor that you are withdrawing your consent for your samples to be used for 
future analyses. This can be done at any time, for any reason. This will not affect your access to the 
care, medicine, and equipment you would otherwise be getting. Your study doctor will then tell the 
sponsor to destroy all your samples when they are no longer needed for the main study.  
If you withdraw your consent for samples to be kept and used after the study is over, it is possible 
that your study doctor may have already discarded the medical records that link your name to your 
study number. In this case, your samples would no longer be linked to you. It would not be possible 
to find your samples to destroy them. 
WHAT HAPPENS TO YOUR SAMPLES IF YOU WITHDRAW FROM THE 
STUDY? 
If you withdraw from the study, the samples and data collected prior to your withdrawal will still be 
used to assess the objectives of the study, to guarantee that your personal interests are not 
negatively affected, and to comply with the requirement to provide complete documentation when 
seeking marketing authorization.  
WHAT WILL HAPPEN IF YOU DON’T WANT TO CARRY ON WITH THE 
STUDY OR THE YOU ARE WITHDRAWN? 
Participation in the study is voluntary. You may refuse to participate in this study, and if you decide 
to participate you may stop at any time without further explanation. This will not affect your future 
treatment or your relationship with your study doctor. If you stop taking part, please tell your study 
doctor immediately. You will be asked to return to the study center for an end-of-study assessment 
If you take back your permission to collect, use, or disclose your personal information, you will be 
withdrawn from the study. If you want to stop participating in the study for any reason or want to 
take back your permission to collect, use or disclose your personal information, you must let the 
study doctor know. 


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IFX-1-P.2.7 
Informed Consent Form 
Version 7.0, 10-Feb-2020 
Page 20 of 23 
 
The study may be stopped early by the sponsor, the study doctor, Research Review Board Inc., or 
organizations that regulate research in Canada or other countries. Under certain circumstances, your 
study doctor might decide to stop your study drug or study participation early without your consent 
when, in the study doctor’s judgment, it is in your best health interest to do so or under certain 
circumstances listed below: 
• Your condition worsens or does not improve and an alternative treatment is medically 
indicated. 
• The study treatment or procedures are found to be unsafe or ineffective. 
• Your inability to take the study drug / participate as instructed. 
• Cancellation by the sponsor or regulatory authority (e.g., if new side effects become known 
that preclude continuation of the clinical study). 
• The study is stopped by the Research Review Board Inc. (RRB) (a group of people who 
review the research to protect your rights) or by a regulatory agency (such as Health 
Canada). 
• Or for other unforeseen reasons that make it necessary to stop your participation in the 
study. 
• If you are removed from the study, the study doctor will explain to you why you were 
removed. 
If you withdraw or are withdrawn from the study: 
• You can’t continue in the study. 
• We will stop collecting new information from you, except for long term follow up as may be 
described in this consent form or pregnancy follow up as described above in the event you 
become pregnant during the study, but will still use and disclose information that we 
gathered while you were a participant in the study. 
• There will not be any penalty or loss of benefits to which you are otherwise entitled. 
If you are withdrawn from the study because you become pregnant, with your permission we will 
continue to follow up and collect information about your pregnancy, as described in this consent 
form. If you do not want to be contacted by your study doctor or have your medical records 
reviewed to collect information on your pregnancy after you have stopped participation in the study, 
you should inform your study doctor about this when you are withdrawn from the study. 
WHAT IF YOU HAVE QUESTIONS AND WHO SHOULD YOU CONTACT 
FOR MORE INFORMATION? 
If you have any questions about your rights as a study patient, please contact your family doctor, 
lawyer, or the committee that reviewed the ethical aspects of this study: 
 


InflaRx 
IFX-1-P.2.7 
Informed Consent Form 
Version 7.0, 10-Feb-2020 
Page 21 of 23 
 
The Research Review Board (RRB) Inc. is a group of people who review research studies to protect 
the rights and welfare of research subjects and is not affiliated with the study doctor or the sponsor. 
If you have any questions concerning your participation in this study, or if at any time you feel you 
have experienced a research-related injury or reaction to the study drug, you may contact: 
Dr. Afsaneh Alavi 
 
In case of an emergency, you may contact Dr. Alavi at the above phone number or go to the nearest 
hospital emergency department. 
 


InflaRx 
IFX-1-P.2.7 
Informed Consent Form 
Version 7.0, 10-Feb-2020 
Page 22 of 23 
 
CONSENT FORM 
Your signature on this form indicates that you have understood to your satisfaction the information 
regarding participation in the research project and agree to participate as a subject. 
You are also authorizing study staff to use and disclose your health information for study purposes. 
In no way does this waive your legal rights nor release the investigators, sponsors, or involved 
institutions from their legal and professional responsibilities. You are free to withdraw from the 
study at any time without jeopardizing the health care you are entitled to receive. 
Do you give your permission to the study doctor to inform your 
family doctor of your participation in this clinical research 
study? 
 YES  NO 
Patient to initial 
Do you give your permission for your stored blood samples to 
be used for future research as described in the section “What 
happens if InflaRx wants to perform other tests on my blood 
samples at a later time”? 
 YES  NO 
Patient to initial 
Your continued participation should be as informed as your initial consent. You will be informed in 
a timely manner if information becomes available that may affect your willingness to continue 
participating in this study. You should also feel free to ask for clarification or new information 
throughout your participation. If you have further questions concerning matters related to this 
research, please contact the study doctor or study staff. 
You will receive a copy of this signed and dated informed consent form. 
Signature of Participant 
Name (printed) 
Date (dd/mmm/yy)* 
Signature of Person Conducting Consent 
Discussion 
Name (printed) 
Date (dd/mmm/yy)* 
If applicable per ICH Guideline Section 4.8.9: 
 
Signature of Witness 
Name (printed) 
Date (dd/mmm/yy)* 
*PLEASE PERSONALLY DATE YOUR SIGNATURE 


InflaRx 
IFX-1-P.2.7 
Informed Consent Form 
Version 7.0, 10-Feb-2020 
Page 23 of 23 
 
INVESTIGATOR’S STATEMENT 
I, or a member of my research staff, have carefully explained to the subject the nature and purpose 
of the above study. The subject signing this form has been given enough time and an adequate place 
to read and review this form. The subject has had an opportunity to ask questions and receive 
answers regarding the nature, risks, and benefits of participation in this research study. The subject 
appears to understand the nature and purpose of the study and the demands required of 
participation. 
 
Signature of Investigator 
Name (printed) 
Date (dd/mmm/yy)