Clinical trial NCT03512275
Conditions: Hidradenitis Suppurativa
Keywords: Hidradenitis Suppurativa
Sponsor: Janssen Research & Development, LLC
Start date: 2018-06-20; Completion date: 2019-01-14
Enrollment: 42 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Phase 2 study of bermekimab in patients with moderate to severe Hidradenitis Suppurativa.

Detailed description:
Phase 2, open label study of bermekimab in patients with moderate to severe Hidradenitis Suppurativa. The study is multicenter and will consist of two patient groups, each of which will receive a total of 13 X 400mg weekly subcutaneous injections of bermekimab: Group A (n=10) patients who have failed anti-TNF therapy, and Group B (n=10) patients who have had no prior treatment with biological agents that block TNF.

Patients will be followed for 13 weeks to allow for assessment of safety and preliminary efficacy.

Additionally, patients who had received the 200 mg weekly subcutaneous injections of bermekimab under the previous version of this protocol are eligible to begin receiving the 400 mg dose starting with his/her next scheduled visit, and for the remainder of his/her treatment plan.

XBiotech owned bermekimab and sponsored and completed study prior to Dec 30, 2019.

Arms: arm 1: N=10 patients that have had no prior treatment with biological agents that block TNF will receive a total of 13 X 400mg subcutaneous injections of bermekimab. Dosing will occur weekly for 12 weeks, inclusive of visit 1 and visit 13. arm 2: N=10 patients that have failed anti-TNF therapy will receive a total of 13 X 400mg subcutaneous injections of bermekimab. Dosing will occur weekly for 12 weeks, inclusive of visit 1 and visit 13.
Interventions: intervention 1: Bermekimab Monoclonal Antibody 400 mg
Intervention descriptions: intervention 1: subcutaneous injection

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Trial Protocol 
A Phase II, Open Label Study of Bermekimab in Patients with 
Moderate to Severe Hidradenitis Suppurativa 
SPONSOR 
XBiotech USA Inc 
 
 
 
 
 
 
 
 
30 August 2018 
NCT03512275


XBIOTECH USA INC.                                                                                           PROTOCOL 2018-PT045 Version 3.1 
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Table of Contents 
BASIC INFORMATION ................................................................................................................ 4 
INVESTIGATOR/SPONSOR SIGNATURES ............................................................................... 5 
CLINICAL PROTOCOL SYNOPSIS............................................................................................. 6 
ABBREVIATIONS ....................................................................................................................... 10 
1.  BACKGROUND ....................................................................................................................... 11 
1.1 OVERVIEW ......................................................................................................................... 11 
1.2 RATIONALE ........................................................................................................................ 12 
2.  INVESTIGATIONAL PRODUCT .......................................................................................... 14 
2.1 ACTIVE INGREDIENT, PHARMACOLOGIC CLASS, STRUCTURE ............................... 14 
2.2 DRUG PRODUCT (BERMEKIMAB 200 MG/ML) DESCRIPTION ................................... 16 
2.3 STORAGE ............................................................................................................................ 17 
2.4 STABILITY ........................................................................................................................... 17 
2.5 METHOD OF ADMINISTRATION ..................................................................................... 17 
2.6 AGENT ORDERING ............................................................................................................ 19 
2.7 POTENTIAL DRUG INTERACTIONS ................................................................................ 19 
2.8 PROHIBITED AND RESTRICTED THERAPIES ............................................................... 19 
3.  STUDY DESIGN AND OBJECTIVES ................................................................................... 19 
3.1 STUDY ENDPOINTS .......................................................................................................... 20 
4.  ELIGIBILITY CRITERIA ...................................................................................................... 21 
4.1 INCLUSION CRITERIA ...................................................................................................... 21 
4.2 EXCLUSION CRITERIA ..................................................................................................... 22 
5.   TREATMENT PLAN .............................................................................................................. 23 
5.1 STUDY PROCEDURES ...................................................................................................... 23 
5.2  STUDY CALENDAR ........................................................................................................... 33 
5.3 DISCONTINUATION OF THERAPY .................................................................................. 34 
5.4 TRIAL STOPPING RULES .................................................................................................. 34 
5.5 PATIENT CROSSOVER RULES ......................................................................................... 34 
6.  CORRELATIVE STUDIES ..................................................................................................... 35 
6.1 PHARMACOKINETICS (PK) SAMPLE COLLECTION .................................................... 35 
7.  ASSESSMENT OF SAFETY .................................................................................................. 35 
8.  STUDY VARIABLES .............................................................................................................. 35 
8.1 DEMOGRAPHIC AND DISEASE CHARACTERISTICS .................................................... 35 
8.2 STUDY ENDPOINTS .......................................................................................................... 36 
9.  ADVERSE EVENTS ................................................................................................................ 37 
9.1 DEFINITION OF ADVERSE EVENT (AE) ......................................................................... 37 
9.2 DEFINITION OF SERIOUS ADVERSE EVENT (SAE) ...................................................... 38 
9.3 RECORDING OF ADVERSE EVENTS ............................................................................... 38 
9.4   EVALUATING ADVERSE EVENTS .................................................................................. 39 
9.5 ASSESSMENT OF CAUSALITY .......................................................................................... 39 
9.6 REPORTING REQUIREMENTS ......................................................................................... 39 
9.7 REFERENCE SAFETY INFORMATION:  POTENTIAL ADVERSE REACTIONS ............ 40 


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10.  STATISTICAL PLAN ............................................................................................................ 41 
10.1 STATISTICAL HYPOTHESIS ............................................................................................ 41 
10.2 DETERMINATION OF SAMPLE SIZE ............................................................................. 41 
10.3 ANALYSIS SETS ................................................................................................................ 42 
10.3.1 SAFETY ANALYSIS SETS ............................................................................................................. 42 
10.4 PATIENT DISPOSITION .................................................................................................. 42 
10.5 STATISTICAL METHODS ................................................................................................ 42 
10.5.1 DEMOGRAPHY AND BASELINE CHARACTERISTICS .................................................. 42 
10.5.2 SAFETY ANALYSIS ........................................................................................................................ 43 
10.5.3 ANALYSIS OF SECONDARY ENDPOINTS: ......................................................................... 44 
10.5.4 PHARMACODYNAMICS (PK) ANALYSIS: ........................................................................... 44 
10.5.5 TREATMENT EXPOSURE ............................................................................................. 45 
11.  STUDY MANAGEMENT AND ADMINISTRATION ......................................................... 45 
11.1 ETHICAL CONDUCT OF STUDY (GCP) ........................................................................ 45 
11.2 IRB AND ETHICS COMMITTEE APPROVAL ................................................................. 45 
11.3 PROTOCOL MODIFICATIONS ....................................................................................... 46 
11.4 SUBJECT INFORMATION AND CONSENT .................................................................... 46 
11.5 DATA PROTECTION AND CONFIDENTIALITY ............................................................ 46 
11.6 STUDY REPORT AND PUBLICATIONS .......................................................................... 47 
11.7 STUDY FILES AND RETENTION OF RECORDS ........................................................... 47 
11.8 CASE REPORT FORMS .................................................................................................... 48 
11.9 DRUG ACCOUNTABILITY .............................................................................................. 48 
11.10   INSPECTIONS ............................................................................................................... 48 
11.11 ACCESS TO INFORMATION FOR MONITORING ....................................................... 49 
11.12 STUDY DISCONTINUATION ......................................................................................... 49 
REFERENCES ............................................................................................................................. 50 
 
 
 


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Basic Information 
 
STUDY TITLE: A Phase II, Open Label Study of Bermekimab in Patients with 
Moderate to Severe Hidradenitis Suppurativa  
 
INVESTIGATIONAL PRODUCT: 
Bermekimab 
 
IND NUMBER: 
 
 
 
112,459 
 
 
 
 
 
 
 
 
PROTOCOL NUMBER: 
 
 
2018-PT045  
 
 
 
 
PROTOCOL VERSION / DATE:  
3.1/ August 30th, 2018 
 
 
 
 
 
SPONSOR:  
 
 
 
XBiotech USA, Inc.  
5217 Winnebago Lane 
Austin, Texas 78744 U.S.A. 
Phone: 737-207-4600 
 
SPONSOR’S MEDICAL OFFICER: 
Mark Williams, M.D., MBA 
5217 Winnebago Lane 
Austin, Texas 78744 U.S.A. 
Phone: 737-207-4612 
 
 
STUDY CHAIR: 
Alice Gottlieb, M.D., Ph.D.  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Investigator/Sponsor Signatures 
 
STUDY TITLE:  A Phase II, Open Label Study of Bermekimab in Patients with Moderate 
to Severe Hidradenitis Suppurativa  
 
STUDY PRINCIPAL INVESTIGATOR SIGNATURE:  
I have read the protocol and appendices. I understand the contents and intend to comply fully with 
all requirements and the applicable current local and international regulations and guidelines. No 
changes will be made without formal authorization by XBiotech USA, Inc., in the form of a 
protocol amendment. 
 
INVESTIGATOR SIGNATURE: 
 
 
_____________________________________________  
Printed name of Investigator  
 
 
_____________________________________________  
Signature  
 
 
_____________________________________________  
Date  
 
SPONSOR SIGNATURE:  
 
XBiotech USA, Inc. 
 
 
____________________________________________  
Printed Name 
 
 
____________________________________________  
Signature 
 
 
____________________________________________  
Date 


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Clinical Protocol Synopsis 
 
Study Title: A Phase II, Open Label Study of Bermekimab in Patients with Moderate to Severe 
Hidradenitis Suppurativa 
 
 
 
Sponsor:   
 
 
 
 
XBiotech USA, Inc. 
 
Study Chair:   
Alice Gottlieb, M.D., Ph.D. 
 
Sample Size: 
 
20 Subjects  
 
Approximate Duration:  The duration of subject participation is approximately 16 weeks, 
including a 3 week screening period, and a 13 week treatment period.  
 
Study Objectives: 
Primary Endpoint(s): 
• 
Safety and Tolerability 
 
Secondary Endpoints: 
• 
Hidradenitis Suppurativa Clinical Response (HiSCR) from baseline (visit 1) to visit 13. 
• 
Assessment of Pharmacokinetics (PK)  
• 
Change in patient reported outcomes from baseline (visit 1) to visit 13 (VAS for disease, VAS 
for pain, DLQI). 
• 
Change in Physician’s Global Assessment (PGA), Disease Activity Score, and modified 
Sartorius score from baseline (visit 1) to visit 13. 
• 
Change in inflammatory lesion (abscesses and inflammatory nodules) count from baseline 
(visit 1) to visit 13. 
• 
Change from baseline (visit 1) to visit 13 in Hospital Anxiety Depression Scale (HADS).  
 
 
 


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Trial Design* 
 
A Phase II, Open Label Study of Bermekimab in Patients with Moderate to Severe Hidradenitis 
Suppurativa 
 
• 
Group A (n=10): patients that have failed anti-TNF therapy will receive a total of 13 X 400mg 
weekly subcutaneous injections of bermekimab.  
• 
Group B (n=10): patients that have no prior treatment with biological agents that block TNF 
will receive a total of 13 X 400mg weekly subcutaneous injections of bermekimab.  
 
*Restricted medications may be administered once during the study to alleviate acute 
exacerbation for HS symptoms.  
 
 
 


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Inclusion Criteria:  
No waivers/exemptions will be granted for protocol inclusion/exclusion criteria. 
 
Subjects are included in the study if they meet all of the following criteria: 
• 
Written informed consent provided by the patient. 
• 
Male or female, age ≥18 years. 
• 
For group A, patients must have received and failed anti-TNF therapy. For group B, subjects must 
not have received any prior treatment with any anti-TNF therapy. 
• 
Patients who have received 200mg dose of Bermekimab in this study are eligible to begin receiving 
400mg dose starting with the patient’s next scheduled visit for the remainder of his/her treatment 
plan. 
• 
Diagnosis of HS for at least 1 year prior to screening. 
• 
HS affecting at least two distinct anatomic areas, one of which is Hurley II or III stage. 
• 
A total body count of abscesses and inflammatory nodules (AN) of at least 3. 
• 
Full understanding of the procedures of the study protocol and willingness to comply with them. 
• 
In case of female patients of childbearing potential, willingness to use one method of contraception 
of high efficacy during the entire study period. This method can be hormonal contraceptives or one 
of the following: condoms, diaphragm, or an intrauterine device. Women of non-childbearing 
potential include those considered to have a medical history that indicates that pregnancy is not a 
reasonable risk, including post-menopausal women and those with a history of hysterectomy. 
 
 


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Exclusion Criteria: 
Subjects with ANY of the following will be excluded from the study: 
 
• 
Age below 18 years. 
• 
Receipt of oral antibiotic treatment for HS within 28 days prior to screening. 
• 
Receipt of prescription topical therapies for the treatment of HS within 14 days prior to screening, 
and/or systemic therapies for HS (immunosuppressants, corticosteroids, retinoids, or hormonal 
therapies) within 28 days prior to screening. 
• 
History of treatment with bermekimab for any reason EXCEPT patients previously treated with 
200mg bermekimab dose in the previous version(s) of this study. 
• 
History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine 
monoclonal antibodies. 
• 
Has received a live (attenuated) vaccine over the 4 weeks prior to screening. 
• 
New intake of opioid analgesics starting within 14 days prior to screening. 
• 
Major surgery (requiring general anesthesia or respiratory assistance) within 28 days prior to Day 0 
of start of study drug. 
• 
Hepatic dysfunction defined as any value of transaminases, of γ-glutamyl transpeptidase (γGT) or 
of total bilirubin > 3x upper normal limit. 
• 
Stage C Child-Pugh liver cirrhosis. 
• 
History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) 
or hepatitis C virus (HCV). 
• 
Neutropenia defined as <1,000 neutrophils/mm3. 
• 
Pregnancy or lactation. 
 
 


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Abbreviations 
 
AE 
 
Adverse event 
ALT 
 
Alanine aminotransferase (ALT, SGPT) 
PT/aPTT  
Prothrombin Time/Activated Partial Thromboplastin Time 
ALP 
 
Alkaline phosphate 
BMI 
 
Body mass index 
BP 
 
Blood pressure 
BSA 
 
Body Surface Area 
CBC 
 
Complete blood count 
CI 
 
Confidence interval 
CH 
 
Heavy chain constant region 
CL 
 
Light chain constant region 
eCRF 
 
Electronic Case report form 
CRA 
 
Clinical Research Associate 
CRP 
 
C-Reactive Protein 
CTCAE  
Common terminology criteria for adverse events 
DLQI 
 
Dermatology Life Quality Index 
EC 
 
Ethics Committee 
ELISA 
 
Enzyme-linked immunosorbent assay 
GCP 
 
Good clinical practice 
GLP 
 
Good laboratory practice 
GMP 
 
Good manufacturing practice 
HADS 
 
Hospital Anxiety Depression Scale 
HbA1c 
 
Hemoglobin A1c 
HBsAg  
Hepatitis B surface antigen 
HiSCR 
 
Hidradenitis Suppurativa Clinical Response Score 
HIV 
 
Human immunodeficiency virus 
IFN-γ 
 
Interferon Gamma 
IGA 
 
Investigator’s Global Assessment 
IgG 
 
Immunoglobulin G 
IL-1 α 
 
Interleukin-1 α 
IL-1β  
 
Interleukin-1 β 
IL-1 RA  
Interleukin-1 receptor antagonist 
IRB 
 
Institutional review board 
PK 
 
Pharmacokinetics 
PGA 
 
Physicians Global Assessment 
pI 
 
Isoelectric Point 
SAE 
 
Serious Adverse Event 
ULN 
 
Upper limit of normal 
UV 
 
Ultraviolet 
VAS 
 
Visual Analog Scale 
WOCBP  
Women of childbearing potential 
 


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1.  BACKGROUND 
1.1 Overview 
XBiotech USA, Inc. has developed a True Human monoclonal antibody, Bermekimab, that binds 
the cytokine IL-1α with high affinity and is an effective blocker of IL-1α biological activity. IL-
1α is a key mediator of sterile inflammatory responses and has been implicated in the pathology of 
advanced cancer, cardiovascular disease, and rheumatologic disease. Clinical evidence generated 
to date suggests that targeting IL-1α may be an effective treatment in undermining the 
inflammatory process that drives a wide array of diseases, including dermatologic conditions. 
 
The active ingredient in the drug product bermekimab is MABp1, a recombinant human IgG1 
monoclonal antibody specific for human interleukin-1α (IL-1α). The entire bermekimab heavy and 
light chain sequences are identical to those found in naturally-occurring human IgG1κ, with the 
light and heavy chain variable regions being identical to those originally expressed by a peripheral 
blood B lymphocyte that was obtained from a healthy individual. No in vitro affinity maturation or 
modifications have been made to improve its natural binding affinity (211 +/- 31 pM). We believe 
that a true human antibody should be effectively non-immunogenic in humans and thus exhibit 
optimal activity and pharmacokinetics.  XBiotech has conducted 10 clinical studies to date using 
the bermekimab antibody.  These studies have been conducted in a wide range of therapeutic areas, 
from cancer to healthy volunteers, and have included a several different dose levels and dosing 
schedules. Both intravenous and subcutaneous formulations have been explored for safety and 
evidence of efficacy. 
 
Three phase 2 studies sponsored by XBiotech have been completed in dermatologic indications 
(acne, psoriasis and pyoderma gangrenosum), along with one investigator sponsored study in 
Hidradenitis Suppurativa1,2,3.  Subjects with moderate to severe psoriasis experienced a rapid 
reduction in their psoriasis area and severity index (PASI), and subjects with acne vulgaris 
experienced reductions of inflammatory lesion counts, as well as reduced hospital anxiety and 
depression scores (HADS). In both of these trials, there were few adverse events, which were all 
grade 1 (mild) and the only events that appeared to be related to therapy were mild injection site 
reactions in two patients.  
 
The investigator initiated study enrolled patients with moderate to severe HS that were refractory 
to or not eligible for treatment with TNF blocking agents.  The study was double blind, randomized 


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and placebo controlled, and utilized the Hidradenitis Suppurativa Clinical Response (HiSCR) score 
as a primary endpoint. Ten patients were randomized to placebo and 10 patients to treatment with 
bermekimab.  A positive HiSCR score after 12 weeks was found in one (10%) and six (60%) 
patients respectively (OR: 13.50; 95%CIs: 1.19-152.61; p: 0.035). After withdrawal of therapy at 
week 12, a positive HiSCR score was found in nil (0%) of the placebo group and four (40%) of the 
treated patients after 24 weeks (p: 0.043).   
 
Endogenous anti-IL-1α antibodies are present in 5% to 28% of the general population4,5,6,7.  No 
negative correlations with disease have been noted for these individuals. To the contrary, the 
presence of natural anti-IL-1α antibodies has been associated with favorable outcomes, both with 
respect to rheumatoid arthritis and ischemic heart disease. Animal studies also indicate that IL-1α 
loss or antagonism does not result in harm. Moreover, the well-tolerated use of other approved 
biological agents that employ alternative other strategies to block IL-1 activity suggest that 
bermekimab’s targeting of IL-1α represents a safe treatment approach.  
 
1.2 Rationale 
 
Hidradenitis suppurativa (HS) is a common disorder affecting areas of the skin rich in apocrine 
glands. HS typically starts at adolescence. The clinical course is characterized by exacerbations and 
remissions of flare-ups. During these flare-ups the affected gland becomes swollen and then 
ruptures, with the discharge of purulent material. The duration of a flare-up is typically 3-5 days 
and is characterized by pain and difficulty in movement. Emotional stress is commonly associated 
with flare-ups, and flare-ups are commonly present in women before menses. As the disease 
progresses, fistulas are formed under the dermis. These fistulas often suppurate continuously8. This 
chronic inflammation and the accompanying pain account for the fact that HS is ranked first among 
skin disorders in terms of adversely affecting quality of life9. 
 
HS is a common disorder. Its prevalence in Europe is 0.97%3 whereas in Denmark this figure is 
reported to be 4%4. A recent review of electronic records in the United States revealed an incidence 
of 11.4 per 100,000 in the general population incidence10. The incidence was 2.5 times higher 
among African Americans than among white Americans11. 
 
Based on findings showing high expression of tumor necrosis factor-alpha (TNFα) in the lesions 
of patients12, the fully humanized monoclonal anti-TNF antibody adalimumab was studied for 


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treatment of HS. Two large-scale randomized clinical studies (RCT) were conducted, designated 
PIONEER I and PIONEER II, which shared a common study design. Following an initial loading 
dose of 160 mg and a second 80 mg dose after two weeks, adalimumab was administered 
subcutaneously at a dose of 40 mg every week, and efficacy was compared to that in placebo-
treated patients. The primary efficacy endpoint for both PIONEER studies was set at 12 weeks of 
treatment. This efficacy endpoint was the achievement of a positive hidradenitis suppurativa 
clinical response (HiSCR) score. After the initial 12-week treatment course, patients allocated to 
placebo were maintained to placebo whereas patients allocated to adalimumab were either switched 
to an open label extension (OLE) arm, or were further randomized to placebo, adalimumab 40 mg 
every other week or adalimumab 40 mg every week. Results showed that a positive HiSCR was 
found in 28.6% of placebo-treated patients and in 41% of adalimumab-treated patients of the 
PIONEER I study and in 27.6% of placebo-treated patients and in 58.9% of adalimumab-treated 
patients in the PIONEER II study13. As stated above, after the first 12 weeks of treatment patients 
initially treated with adalimumab could be further randomized and received another 12 weeks of 
treatment with placebo, 40mg adalimumab weekly or every other week. Analysis showed that 
approximately half of patients showed a positive initial response to treatment, and half of these 
maintained this response long-term. As also stated above, after the first 12 weeks of treatment, 88 
patients were switched to an OLE receiving 40 mg of adalimumab every week; positive HiSCR 
was achieved at weeks 120 and 168 in 56.8% and 52.3% respectively14. Adalimumab has been 
registered in both USA and Europe for moderate to severe HS based on the results of the two 
PIONEER studies. 
 
Adalimumab is an important advance for the treatment of HS. However, there remains considerable 
unmet need for patients with HS, including 41% to 58% of patients who have primary response 
failures after 12 weeks of adalimumab treatment and the 30-50% patients that have a positive initial 
response to treatment but relapse after 12 weeks of therapy. These primary and secondary failures 
to adalimumab treatment may reflect the biological heterogeneity of the HS.  About half of patients, 
for example, over-express TNFα in their lesions, whereas others have lesions better characterized 
by the production of cytokines like interleukin (IL)-1β and IL-1α15. In a small randomized study 
ten patients were allocated to treatment with placebo and nine patients to treatment with anakinra 
(IL-1 receptor antagonist targeting both IL-1β and IL-1α). A positive HiSCR score was achieved 
in 30% and 78% of patients, respectively (p: 0.039)16. These results suggested that inhibition of IL-
1 may be a promising treatment strategy, including that for patients evidencing primary or 
secondary failure of adalimumab.   


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An investigator initiated phase II RCT trial among patients not eligible for adalimumab (EudraCT 
number 2015-002321-20; ClinicalTrials.gov NCT02643654) was recently completed and showed 
promising results for activity of bermekimab in HS. Twenty patients with severe HS and with either 
primary or secondary failure of previous antiTNF agents, or who were unwilling to receive 
subcutaneous adalimumab treatment, were randomly allocated (1:1) to receive, in a blinded fashion, 
every other week treatment with placebo or bermekimab at a dose of 7.5 mg/kg IV. Treatment was 
administered intravenously for 12 weeks.  The primary efficacy endpoint was the positive HiSCR 
score, that was achieved among 10% of patients allocated to placebo and 60% of patients allocated 
to bermekimab. The odds ratio for positive HiSCR after 12 weeks of treatment was 13.50 (95% 
confidence intervals 1.19-152.51, p: 0.035). Analysis of the secondary endpoints showed some 
remarkable advantages of bermekimab treatment versus placebo treatment: a) blind follow-up for 
12 weeks after stopping treatment showed that clinical efficacy was sustained, in that a positive 
HiSCR score was found in 40% of the treatment group and 0% of patients receiving placebo (p: 
0.043); b) positive patient reported outcomes were found at week 12 in 70% and 30% respectively 
(p: 0.010); c) the median time to new HS flare-up was prolonged to 11 weeks and 7 weeks 
respectively; d) with the use of dermal ultrasound at week 12, a 20% or more decrease in total depth 
of involved skin lesions was found in 77.8% and 22.2%, respectively (p: 0.029); and e) serum IL-
8 was decreased at week 12 in 90% and 40% respectively (p: 0.029)17. 
 
In previous dermatology studies bermekimab was well tolerated and showed impressive therapeutic 
activity. Dose ranging for the subcutaneous formulation of bermekimab is now being studied in a 
12 week open label treatment regimen for HS in order to establish the basis for further randomized 
studies using subcutaneous administration. 
 
 
2.  INVESTIGATIONAL PRODUCT 
2.1 ACTIVE INGREDIENT, PHARMACOLOGIC CLASS, STRUCTURE 
The active ingredient in the drug product bermekimab is MABp1, a recombinant human IgG1 
monoclonal antibody specific for human interleukin-1α (IL-1α). The entire bermekimab heavy and 
light chain sequences are identical to those found in naturally-occurring human IgG1κ, with the 
light and heavy chain variable regions being identical to those originally expressed by a peripheral 
blood B lymphocyte that was obtained from a healthy individual. 


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Figure 2.1: Bermekimab Antibody 
 
 
 
The bermekimab primary glycoform has a molecular weight of 148.1 kilodaltons. Like all IgG1 
molecules, the heavy chains are joined at their hinge regions through two disulfide linkages, and 
each heavy chain is joined to one light chain through one disulfide linkage between their CH1 and 
CL domains respectively. 
 
The main isoform has a pI of about 9.2 and comprises about 70-80% of the total isoform population 
in all lots that have been manufactured to date, as determined by capillary isoelectric focusing. The 
heavy chain CH2 domains are glycosylated primarily with the oligosaccharide structure shown in 
Figure 2.1, as determined by mass spectroscopy of the cleaved glycans. The glycosylated residue 
(Asn-302 as numbered from the N-terminus of bermekimab) has been determined by peptide 
mapping to be in the same highly conserved N-linked glycosylation site as found in endogenous 
IgG1 (Asn-297 according to the generic numbering system). Similarly, the primary glycan, 
commonly referred to as G0F, is the same as that found on about 22% of endogenous human IgG 
molecules18.  
 
The entire bermekimab heavy and light chain sequences are identical to those found in naturally-
occurring human IgG1κ, with the light and heavy chain variable regions being identical to those 
originally expressed by a peripheral blood B lymphocyte that was obtained from a healthy 
individual.   
 
Endogenous anti-IL-1α antibody has been reported in 5% to 28% of healthy serum or plasma 
samples19,20. It has been measured in cord blood, children and adults21. The anti-IL-1α antibodies 


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measured in human plasma have been strictly of the IgG class, particularly IgG1, IgG2, and IgG4. 
Relatively equal distribution is seen in male and female plasma22. Binding affinities reported for 
endogenous anti-IL-1α antibodies, ranging from 4 to 16 pM.  
  
It is important to point out that affinity maturation had already taken place in the human host, and 
therefore no in vitro affinity maturation was required to increase the natural binding affinity of 
bermekimab. Also important is the fact that, unlike most other therapeutic IgG products, for which 
the Fc regions are derived from a rare human allele, XBiotech’s product includes a heavy chain in 
which the constant (CH) region represents an allele found in approximately 70% of the human 
population. These two features should make for a drug product with reduced potential for 
immunogenicity. 
 
2.2 Drug Product (Bermekimab 200 mg/ml) Description 
XBiotech’s dosage form is a sterile liquid formulation of 200 mg/mL bermekimab in a stabilizing 
isotonic subcutaneous formulation buffer at pH 6.2-6.5.   The drug product is packaged in pre-filled 
syringes. The syringes used are OMPI EZ-Fill Nexa, 2.25mL 27G, ½ inch length needle, or a 
comparable alternative.  The syringe is clear borosilicate type 1 glass containing 2mL of the 
formulation and is sealed using a West 1-3mL Novapure piston (plunger) with Flurotec coating. 
The needle is an AISI 304 stainless steel thin wall device. Drug product in syringes is stored at 
5±3°C and is recommended to be protected from light. 
 
Up to 6 syringes will be packaged in each carton. 
 
Composition Drug Product 200mg/mL in 2 mL syringes 
Ingredient 
Ingredient 
Function 
Grade 
Manufacturer 
Concentration 
Amount per 2 
mL syringe 
Bermekimab 
Antibody 
Active 
Substance 
GMP 
XBiotech USA 
Inc. 
200 mg/mL 
400 mg 
Trehalose 
Dihydrate 
Tonicity 
GMP, 
USP/NF, 
EP, low 
endotoxin 
Ferro-Pfanstiehl 
(USA) 
60 mg/mL 
120 mg 
Sodium 
Phosphate 
Dibasic 
pH Buffering 
Capacity 
GMP, EP, 
USP 
JT Baker (USA) 
12 mg/mL 
24 mg 
Citric Acid 
Monohydrate 
pH Buffering 
Capacity 
GMP, EP, 
USP, BP, 
JP 
Fisher (USA) 
2 mg/mL 
4 mg 
Water for 
Injection 
Solvent 
GMP, EP, 
USP 
Irvine Scientific 
(USA) 
q.s. 
q.s. 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 17 of 50 
 
Phosphoric Acid 
pH adjustment 
GMP, EP, 
USP 
JT Baker (USA) 
pH adjustment 
pH adjustment 
Sodium 
Hydroxide,  
pH adjustment 
GMP, EP, 
USP 
JT Baker (USA) 
pH adjustment 
pH adjustment 
 
2.3 STORAGE 
The recommended storage condition is at 2-8°C.    
 
2.4 STABILITY 
The drug product is formulated in a buffer in which most of the tonicity comes from trehalose rather 
than salt. Trehalose is an effective stabilizer against oxidation, aggregation, thermal, and 
mechanical stress. Citrate was selected as the buffering agent due to its antioxidant properties. 
 
Extensive stability data indicates that the drug product is very stable, even under thermally and 
mechanically stressed conditions. Short excursions to room temperature have shown no negative 
effect on the product. However, the study treatment products are not to be frozen at any time.  The 
200 mg/ml drug product is labeled with a 12-month retest date.  Every lot of 200mg/ml dosage 
form is also subjected to ongoing stability analysis per ICH guidelines.  
 
2.5 METHOD OF ADMINISTRATION 
Patients in Groups A and B will receive 400 mg administered weekly by subcutaneous injection. 
Each injection should be located at least one inch from previous injection sites.   
 
* At least 45 minutes prior to injection, remove the pre-filled syringe from 
refrigeration   
Lay the syringe on a flat surface and let it naturally warm to room temperature before 
injection. Do not heat the syringe. 
 
Materials 
Bermekimab pre-filled syringe for injection, warmed to room temperature* 
Sterile alcohol wipes 
Band-aids, along with 2x2 gauze bandages and paper tape 
Latex-free gloves 
 
Injection Site 
Determine Injection site, see illustration below:  


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CONFIDENTIAL                                        30 August 2018                                            PAGE 18 of 50 
 
Abdomen, at least 2 inches away from the belly button, is the recommended injection site for 
patients with a body mass index (BMI) below 30.  (This measurement is calculated at Screening.)  
Front Thigh or Upper Arm is the recommended injection site for patients with a BMI of 30 or 
more.   
(Note: avoid areas where the skin is burned, scarred, hardened, inflamed, swollen, or damaged). 
 
Injection 
• 
Put on gloves 
• 
Wipe injection site clean with alcohol pads 
• 
Raise a fold of skin between the thumb and forefinger (see illustration below).  
 
• 
Insert needle as illustrated above 
• 
Inject drug slowly  
• 
Withdraw needle. Place band-aid over injection site if necessary (Note: If bleeding 
occurs, hold pressure on the injection site for 90 seconds or until bleeding stops, and 
then apply gauze bandage secured by tape). 
 


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2.6 AGENT ORDERING 
The Responsible Investigational Pharmacy will order study drug from XBiotech as needed. 
 
2.7 POTENTIAL DRUG INTERACTIONS 
There are no known drug interactions with bermekimab. In controlled trials that combined the use 
of IL-1ra (anakinra) with TNF alpha inhibitors, a higher incidence of serious infection was noted. 
Bermekimab has not been administered concomitantly with these agents in clinical trials. However, 
due to potential risk, it is not recommended that bermekimab be used in combination with anti-
TNF agents.   
 
2.8 PROHIBITED AND RESTRICTED THERAPIES 
Treatment with certain restricted concomitant medications is allowed once during study to treat 
acute HS exacerbation, including: 
• 
Systemic therapies with known effectiveness in HS, including corticosteroids, retinoids, or 
anti-androgen (hormonal) therapies. 
• 
Intralesional/topical steroids 
• 
Laser/light therapies 
The use of rescue medications for worsening HS is to be reported in the electronic data capture 
system. A second flare up of disease and subsequent use of a second rescue therapy for any patient 
will result in the patient being treated as a non-responder for the purposes of data analysis.  
 
The following concomitant therapies are prohibited for the entire duration of the trial: 
• 
Biologics that target IL-1 or TNF-alpha 
• 
Live virus vaccines  
• 
Investigational agents other than bermekimab 
 
 
3.  STUDY DESIGN AND OBJECTIVES 
Phase 2, Open label, multicenter study of two dose cohorts of bermekimab in patients naïve to or 
having failed prior anti-TNF therapy with moderate to severe Hidradenitis Suppurativa. 
Bermekimab administered subcutaneously at a dose of 400 mg weekly (13 doses).  Patients will be 
followed for 13 weeks to allow for assessment of safety and preliminary efficacy. 
 


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The study protocol will be approved by the Institutional Review Board (IRB) or the Ethics 
Committee (EC) of the participating study sites. Depending on the participating countries both local 
and central IRB/EC approvals will be granted. The study will be registered at 
www.clinicaltrials.gov before the enrollment of the first patient.  The trial will be conducted in 
compliance with the protocol, GCP, and all applicable regulatory requirements. 
 
3.1 Study Endpoints 
 
Primary Endpoint: 
• 
Safety and Tolerability 
 
Secondary Endpoints: 
• 
Hidradenitis Suppurativa Clinical Response (HiSCR) from baseline (visit 1) to visit 13. 
• 
Assessment of Pharmacokinetics (PK)  
• 
Change in patient reported outcomes from baseline (visit 1) to visit 13 (VAS for disease, VAS 
for pain, DLQI). 
• 
Change in Physician’s Global Assessment (PGA), Disease Activity Score, and modified 
Sartorius score from baseline (visit 1) to visit 13. 
• 
Change in inflammatory lesion (abscesses and inflammatory nodules) count from baseline 
(visit 1) to visit 13. 
• 
Change from baseline (visit 1) to visit 13 in Hospital Anxiety Depression Scale (HADS). 
  


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CONFIDENTIAL                                        30 August 2018                                            PAGE 21 of 50 
 
4.  ELIGIBILITY CRITERIA 
 
4.1 INCLUSION CRITERIA 
No waivers/exemptions will be granted for protocol inclusion/exclusion criteria. 
 
Subjects are included in the study if they meet all of the following criteria: 
• 
Written informed consent provided by the patient. 
• 
Male or female, age ≥18 years. 
• 
For group A, patients must have received and failed anti-TNF therapy. For group B, subjects must 
not have received any prior treatment with any anti-TNF therapy. 
• 
Patients who have received 200mg dose of bermekimab in this study are eligible to begin receiving 
400mg dose starting with the patient’s next scheduled visit for the remainder of his/her treatment 
plan. 
• 
Diagnosis of HS for at least 1 year prior to screening. 
• 
HS affecting at least two distinct anatomic areas, one of which is Hurley II or III stage. 
• 
A total body count of abscesses and inflammatory nodules (AN) of at least 3 
• 
Full understanding of the procedures of the study protocol and willingness to comply with them. 
• 
In case of female patients of childbearing potential, willingness to use one method of contraception 
of high efficacy during the entire study period. This method can be hormonal contraceptives or one 
of the following: condoms, diaphragm, or an intrauterine device. Women of non-childbearing 
potential include those considered to have a medical history that indicates that pregnancy is not a 
reasonable risk, including post-menopausal women and those with a history of hysterectomy. 
 
 
 
 


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4.2 EXCLUSION CRITERIA 
Subjects will be excluded from the study if they meet any of the following criteria: 
• 
Age below 18 years. 
• 
Receipt of oral antibiotic treatment for HS within 28 days prior to screening. 
• 
Receipt of prescription topical therapies for the treatment of HS within 14 days prior to screening, 
and systemic therapies for HS (immunosuppressants, corticosteroids, retinoids, or hormonal 
therapies) within 28 days prior to screening. 
• 
History of treatment with bermekimab for any reason EXCEPT patients previously treated with 
200mg bermekimab dose in the previous version(s) of this study. 
• 
History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine 
monoclonal antibodies. 
• 
Administration of any live (attenuated) vaccine over the last 4 weeks. 
• 
New intake of opioid analgesics starting within 14 days prior to screening. 
• 
Major surgery (requiring general anesthesia or respiratory assistance) within 28 days prior to visit 
1, Day 0 of start of study drug. 
• 
Hepatic dysfunction defined as any value of transaminases, of γ-glutamyl transpeptidase (γGT) or 
of total bilirubin> 3 x upper normal limit 
• 
Stage C Child-Pugh liver cirrhosis. 
• 
Chronic infection by the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and 
hepatitis C virus (HCV). 
• 
Neutropenia defined as <1,000 neutrophils/mm3. 
• 
Pregnancy or lactation. 
 


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5.   TREATMENT PLAN 
5.1 STUDY PROCEDURES 
Screening (maximum 21 days):  The screening period begins once the informed consent is 
signed.   
 
Informed Consent 
• 
Demographics 
• 
Medical History 
• 
Concomitant Medications 
• 
Physical Exam  
• 
Vital Signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
• 
Height 
• 
Weight 
• 
Body Mass Index (BMI) [BMI= weight (kg)/height (m2)] 
• 
Blood Draw: 
o Chemistry panel: Albumin, Alkaline Phosphatase, ALT, AST, GGT, 
Bicarbonate (CO2), Calcium, Chloride, Creatinine, Glucose, Potassium, 
Sodium, Total Bilirubin, Total Protein, Urea Nitrogen 
o Hematology Panel:  Complete Blood Count (CBC) with differential and 
platelets 
o Infectious disease screening: HIV antibody, Hepatitis C antibody, 
Hepatitis B panel (HBsAg, anti-HBc, anti-HBs), and interferon gamma 
release assay (IGRA) 
o Serum pregnancy test for WOCBP 
o Inflammation Markers: CRP (C-Reactive Protein), ESR (Erythrocyte 
Sedimentation Rate) 
 
Visit 1 (day 0, must occur within 21 days of signing informed consent): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Physical Exam 
o DLQI 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 24 of 50 
 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
o Blood draw for PK and biomarker analysis 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 2 (day 7 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 


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Visit 3 (day 14 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
o Blood draw for chemistry, hematology, CRP, ESR and blood draw for PK and 
biomarker analysis 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 4 (day 21 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 26 of 50 
 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 5 (day 28 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Blood draw for chemistry, hematology, CRP, ESR and blood draw for PK and 
biomarker analysis 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 


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Visit 6 (day 35 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
 
 
Visit 7 (day 42 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 28 of 50 
 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 8 (day 49 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 9 (day 56 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 29 of 50 
 
o HADS 
o VAS for disease 
o VAS for pain 
o Blood draw for chemistry, hematology, CRP, ESR and blood draw for PK and 
biomarker analysis 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 10 (day 63 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 11 (day 70 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 


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CONFIDENTIAL                                        30 August 2018                                            PAGE 30 of 50 
 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 
 
Visit 12 (day 77 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre-injection 
o Urine pregnancy 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening 
 
1 hour monitoring for injection reaction 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes) 
 
Adverse event monitoring 
 
Concomitant medications/treatments 


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Visit 13 (day 84 +/-2): 
 
At least 45 minutes before injection:  Remove syringe from refrigeration and lay flat; allow 
to warm to room temperature.  Do not heat 
 
Pre Injection 
o Physical Exam 
o DLQI 
o Urine pregnancy 
o HISCR 
o PGA 
o Disease Activity Score 
o Modified Sartorius 
o HADS 
o VAS for disease 
o VAS for pain 
o Blood draw for chemistry, hematology, CRP, ESR and blood draw for PK and 
biomarker analysis 
o Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) 
 
Bermekimab subcutaneous injection, in accordance with injection site determined by BMI 
at Screening  
 
1 hour monitoring for injection reactions  
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature) one hour post injection (70 +/- 10 minutes)  
 
Adverse event monitoring  
 
Concomitant medications/treatments 
 
Visit 14 (day 91 +/-2): 
 
Physical Exam 
 
DLQI 
 
HISCR 
 
PGA 
 
Disease Activity Score 
 
Modified Sartorius 


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 
HADS 
 
VAS for disease 
 
VAS for pain 
 
Vital signs (blood pressure, pulse, oxygen saturation, respiratory rate and body 
temperature)  
 
Adverse event monitoring  
 
Concomitant medications/treatments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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5.2  STUDY CALENDAR  
 
Visit 
Screen 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Study Day 
 
0 
7 
± 
2 
14 
± 
2 
21 
± 
2 
28 
± 
2 
35 
± 
2 
42 
± 
2 
49 
± 
2 
56 
± 
2 
63 
± 
2 
70 
± 
2 
77 
± 
2 
84 
± 
2 
91 
± 
2 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/ Surgical 
History 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious Disease 
Panel✢ (part of blood 
draw) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum Pregnancy 
(part of blood draw) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height, Weight, 
Body Mass Index 
(BMI) 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital Signs▵ 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Urine Pregnancy 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
PK & Biomarker 
Blood Draw 
 
x 
 
x 
 
x 
 
 
 
x 
 
 
 
x 
 
Bermekimab 
Injection❖  
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
DLQI 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
HADS 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
Physical Exam 
x 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
Lab Blood Draw a,b,c 
x  
 
 
x 
 
x 
 
 
 
x 
 
 
 
x 
 
HiSCR 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
PGA 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
Disease Activity 
Score 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
Modified Sartorius 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
VAS for disease 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
VAS for pain 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
 
x 
x 
Adverse Events 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Concomitant 
Medications* 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
aChemistry Panel including: Albumin, Alkaline Phosphatase, ALT, AST, GGT, Bicarbonate (CO2) Calcium, 
Chloride,  Creatinine, Glucose, Potassium, Sodium, Total Bilirubin, Total Protein, Urea Nitrogen 
bHematology Panel including: Complete whole blood (WBC, HgB, Platelet, differential) 
c CRP (C-Reactive Protein) and ESR (Erythrocyte Sedimentation Rate) 
✢ HIV antibody, Hepatitis C antibody, Hepatitis B panel (HBsAg, anti-HBc, anti-HBs), and interferon gamma 
release assay (IGRA)  
▵Vital signs include blood pressure, pulse, oxygen saturation, respiratory rate and body temperature 
❖Each bermekimab injection will be followed by 1 hour monitoring for injection site reaction and vital signs 1 
hour post injection (70+/- 10 minutes) 
* Concomitant medications within 30 days before screening until 7 days after the last administration of the study 
drug must be recorded for the purpose of drug-drug and drug-disease interaction evaluation and signal detection. 
 
BMI: Body Mass Index [BMI= weight (kg)/height (m2)] 
DQLI: Dermatology Quality of Life Index 
HiSCR: Hidradenitis Suppurativa Clinical Response Score 


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PGA: Physicians’ Global Assessment 
VAS: Visual Analogue Scale 
HADS: Hospital Anxiety Depression Scale 
 
5.3 DISCONTINUATION OF THERAPY 
If a patient is discontinued from study, the reason for discontinuation must be clearly documented 
in the source documentation and the EDC. 
Study therapy MUST immediately be discontinued for any the following reasons:  
 
Withdrawal of informed consent (subject’s decision to withdraw for any reason)  
 
Any clinical adverse event, laboratory abnormality, inter-current illness, or clinical progression 
of disease which, in the opinion of the Principal Investigator, indicates that continued 
participation in the study is not in the best interest of the subject  
 
Pregnancy  
 
Termination of the study by the sponsor 
 
Imprisonment or the compulsory detention for medical treatment. 
 
5.4 TRIAL STOPPING RULES 
Enrollment of any further patients for the trial will be suspended for the following events: 
• 
The death of a subject at any time during the trial that is deemed to be probably or definitely 
related to the administration of bermekimab. 
• 
Any significant safety finding assessed as definitely related to bermekimab that in the 
opinion of an Investigator warrants stopping the trial for additional assessment of safety. 
• 
The occurrence of 2 or more serious adverse events occurring in one patient that are 
probably or definitely related to the administration of bermekimab. 
 
5.5 PATIENT CROSSOVER RULES 
Patients enrolled in the 200mg dose study are eligible to receive 400mg bermekimab 
injections upon consent to this protocol. Upon consent, patients will begin 400mg 
bermekimab dosing at next Study Day Visit, following patient calendar so that total 
number of bermekimab injections, 200mg + 400mg, is equal to 13 at end of study. 
 
 
 


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6.  CORRELATIVE STUDIES 
6.1 PHARMACOKINETICS (PK) SAMPLE COLLECTION 
 
An enzyme-linked immunosorbent assay (ELISA) has been developed to specifically measure 
bermekimab levels in human plasma. Blood will be drawn into a single 6 ml collection tube at each 
PK collection time point (sample collection is pre-dose at visit 1, visit 3, visit 5, visit 9 and visit 
13). These samples will be collected per the study lab manual and immediately shipped to the 
Sponsor for PK analysis. The PK samples will also be used to test for the presence of antibodies 
against bermekimab. 
 
 
7.  ASSESSMENT OF SAFETY 
Safety will be assessed by monitoring adverse events, vital signs, physical examinations, and 
clinical laboratory measurements. All subjects will be included in the safety analysis.  Adverse 
events will be monitored from visit 1 (post-injection) through visit 14.  Any serious adverse events 
or grade 2 or greater probably or definitely related events will be followed up until resolution. 
 
Study drug will be administered under close observation in a facility equipped to handle 
anaphylaxis. Subjects must be closely monitored until at least 1 hour following the administration 
of the antibody or 1 hour after their vital signs have stabilized.     
 
Any AE (with the exception of worsening HS symptoms or injection site reactions) of grade 2 or 
higher must be reported to the sponsor within 24 hours of learning of the event.  Any grade 3 or 
greater injection site reaction must be reported to the sponsor within 24 hours of learning of the 
event. 
 
 
8.  STUDY VARIABLES 
 
8.1 Demographic and Disease Characteristics 
 
Demographic characteristics will include standard demography (age, sex, race, height, weight, and 
BMI) medical history, medication history, and prior biologic use for each patient.  Characteristics 
of the patients with hidradenitis suppurativa, including duration of disease, baseline disease severity 
scores (HiSCR, modified Sartorius score, and physician’s global assessment), baseline 
inflammatory lesion counts (abscesses and inflammatory nodules), and baseline patient reported 


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outcomes (VAS for pain, VAS for disease severity, and DLQI), will be collected.  Baseline is 
defined as the visit 1, pre-injection assessment. 
8.2 Study Endpoints 
 
The primary endpoint of this study is the safety and tolerability of bermekimab at 400 mg weekly 
subcutaneous dose. 
 
The secondary endpoints include: 
• 
Hidradenitis Suppurativa Clinical Response (HiSCR) score (baseline to visit 13). For this score 
patients are defined as achievers or non-achievers. The positive HiSCR score is defined as a 
≥ 50% reduction in inflammatory lesion AN count (sum of abscesses and inflammatory 
nodules), and no increase in abscesses or draining fistulas in HS compared with the lesions 
counted on visit 123. The HiSCR score, including inflammatory lesion count, will be measured 
on visits 1, 3, 5, 7, 9, 11, 13 and 14. 
• 
Pharmacokinetics (PK) (baseline to visit 13). An enzyme-linked immunosorbent assay 
(ELISA) has been developed to specifically measure bermekimab levels in human plasma. 
Blood will be drawn into a single 6 ml collection tube at each PK collection time point (sample 
collection is pre-dose at visit 1, visit 3, visit 5, visit 9 and visit 13). These samples will be 
collected per the study lab manual and immediately shipped to the Sponsor for PK analysis. 
The PK samples will also be used to test for the presence of antibodies against bermekimab. 
• 
Physician’s Global Assessment (PGA) (baseline to visit 13). This is defined as: a) clear when 
the total number of abscesses is 0, the total number of draining fistulas is 0, the total number 
of inflammatory nodules is 0 and the total number of non-inflammatory nodules is 0; b) 
minimal when the total number of abscesses is 0, the total number of draining fistulas is 0, the 
total number of inflammatory nodules is 0 and there is presence of non-inflammatory nodules; 
c) mild when the total number of abscesses is 0, the total number of draining fistulas is 0, and 
the total number of inflammatory nodules is 1-4, or when there is presence of one abscess or 
draining fistula  and absence of any inflammatory nodules; d) moderate when the total number 
of abscesses is 0, the total number of draining fistulas is 0 and the total number of inflammatory 
nodules is at least 5; or when there is presence of one abscess or draining fistula and at least 
one inflammatory nodule; or when there are 2-5 abscesses or draining fistulas and fewer than 
10 inflammatory nodules; e) severe when the total number of abscesses or draining fistulas is 
2-5 and the total number of inflammatory nodules is at least 10; and f) very severe when there 


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are more than 5 abscesses or draining fistulas24.  The PGA will be measured on visits 1, 3, 5, 
7, 9, 11, 13 and 14. 
• 
Disease Activity Score (baseline to visit 13). This is defined as the sum of scores of all affected 
areas of each patient. Each area will be evaluated by the following formula: (multiplication of 
the two largest diameters in each affected area in mm) x (the degree of inflammation of each 
lesion). This score has been proposed by our study group25. The Disease Activity Score will be 
measured on visits 1, 3, 5, 7, 9, 11, 13 and 14. 
• 
The modified Sartorius score (baseline to visit 13). The Sartorius Scale is used to quantify the 
severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right 
sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-
crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points 
for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and 
longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated 
by normal skin (yes-0 points; no-6 points). The total Sartorius score is the sum of the 12 
regional scores. The modified Sartorius score will be measured on visits 1, 3, 5, 7, 9, 11, 13 
and 14. 
• 
Change in AN count (baseline to visit 13). The sum of abscesses and inflammatory nodules for 
each patient will be measured on visits 1, 3, 5, 7, 9, 11, 13 and 14. 
• 
Change in VAS for Disease Severity and Pain (baseline to visit 13). Patient reported visual 
analogue scales for pain and disease severity will be measured on visits 1, 3, 5, 7, 9, 11, 13 and 
14. 
• 
Change in Dermatology Life Quality Index (DLQI) (baseline to visit 13). This will be measured 
on visits 1, 3, 5, 7, 9, 11, 13 and 14. 
• 
Change in Hospital Anxiety Depression Scale (HADS) (baseline to visit 13). This will be 
measured on visits 1, 3, 5, 7, 9, 11, 13 and 14. 
Changes in secondary endpoints will be presented by individual cohort, as well as combined across 
both cohorts. 
 
9.  ADVERSE EVENTS  
9.1 DEFINITION OF ADVERSE EVENT (AE) 
An adverse event is defined as any untoward medical occurrence in a subject participating in a 
clinical study that does not necessarily have a causal relationship with the pharmaceutical or 
biological agent under study.  An AE can therefore be any of the following: 


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• 
Any unfavorable and unintended sign (including laboratory findings), symptom, or disease 
temporally associated with the use of bermekimab, whether or not it is apparently related to 
bermekimab; 
• 
A concurrent illness; 
• 
An exacerbation, or an unexpected increase in frequency or intensity of a preexisting 
condition, including intermittent or episodic conditions.   
• 
A significant or unexpected worsening of the condition/indication under investigation.   
• 
A suspected interaction between the investigational drug and concomitant medications 
• 
Any clinically significant laboratory abnormality (including radiological interpretations, 
histopathological findings, etc.) 
 
9.2 DEFINITION OF SERIOUS ADVERSE EVENT (SAE) 
A serious adverse event is defined as any untoward medical occurrence that meets any of the 
following criteria:  
• 
Results in death; 
• 
Life-threatening; 
• 
Requires or prolongs inpatient hospitalization; 
• 
Results in a persistent or significant disability; 
• 
An important medical event that, while it may not result in death or be immediately life-
threatening or require/prolong hospitalization, may jeopardize the subject and/or may require 
medical or surgical intervention to prevent one of the outcomes listed above. Examples of 
such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization. 
 
Note that seriousness and severity should not be confused. A subject could experience a severe 
headache that would not qualify as an SAE, while another might experience a mild stroke that, 
while not severe, would be considered serious. 
 
9.3 RECORDING OF ADVERSE EVENTS 
All untoward events occurring between visit 1 and visit 14 (or if subject terminates from study prior 
to visit 14, seven days after the last administration of bermekimab) on the eCRF, regardless of 
whether they are considered related to study drug. 
 


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All AEs should be recorded in a standard medical terminology as concisely as possible.  The AE 
recorded should not be a procedure or a clinical/laboratory measurement but should reflect the 
event leading to the procedure or the cause of the clinical/laboratory abnormality, if known.  
Whenever possible, AEs should be evaluated and recorded as a diagnosis, rather than individual 
signs and symptoms.  However, if a definitive diagnosis is not possible, the individual signs and 
symptoms should be recorded.  Any AE that worsens in intensity, or becomes serious, should be 
recorded as a new event. 
 
9.4   EVALUATING ADVERSE EVENTS 
All AEs will be graded according to the CTCAE version 4.03. 
 
9.5 ASSESSMENT OF CAUSALITY 
Investigators are required to assess the relationship, if any, of each AE or SAE to the investigational 
drug using clinical judgment to determine the degree of certainty with which an AE can be 
attributed to the investigational drug.  Alternative causes, such as natural history of the underlying 
disease, other risk factors, and the temporal relationship of the event to the administration of the 
study medication must be considered. 
 
Relationship to study drug is summarized as follows: 
• 
Not Related:  There is another obvious cause of the AE 
• 
Unlikely to be related:  There is another more likely cause of the AE 
• 
Possibly related:  The AE could have been due to the investigational drug 
• 
Probably related:  The AE is probably attributable to the investigational drug 
• 
Definitely related:  The AE is most likely attributable to the investigational drug 
 
9.6 REPORTING REQUIREMENTS  
Any AE (with the exception of worsening HS symptoms or injection site reactions) of grade 2 or 
higher must entered into the eCRF within 24 hours of learning of the event.  Any grade 3 or greater 
injection site reaction must be reported to the sponsor within 24 hours of learning of the event. 
 
All serious adverse events (SAEs) should be reported to the Sponsor within 24 hours of knowledge 
of the event.  These immediate reports should be followed promptly by detailed, written reports. 
The subject should be followed up with until stabilization of the reported SAE, either with full 


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satisfactory resolution or resolution with sequelae, or until death of the subject.  Before declaring 
the subject is lost to follow-up, three unsuccessful attempts at contact should be made and recorded 
on the SAE form. The immediate and follow-up reports should identify subjects by unique code 
numbers assigned to the trial subjects rather than by the subjects' names, personal identification 
numbers, and/or addresses. The Investigator should also submit SAEs to the IRB/EC according to 
their IRB/EC guidelines [ICH-GCP E6].  Drug-related Serious Adverse Events will be reported to 
the FDA by XBiotech’s Medical Safety Officer according to 21 CFR 312.32. 
 
9.7 REFERENCE SAFETY INFORMATION:  POTENTIAL ADVERSE REACTIONS 
831 patients have been treated using bermekimab in patients with advanced solid tumors, advanced 
hematologic malignancies, metastatic colorectal cancer, peripheral vascular disease, type II 
diabetes, acne vulgaris, plaque psoriasis, and pyoderma gangrenosum.  Over 1200 doses of 
bermekimab were administered at 7.5 mg/kg to refractory, metastatic CRC patients with cancer 
associated symptoms at baseline (ECOG performance status 1 and 2).  In this trial (PT026), which 
is the largest controlled trial completed with bermekimab to date (N=309), patients were dosed at 
7.5 mg/kg for metastatic colorectal cancer.  The most common AEs reported (>10%) were 
abdominal pain, peripheral edema, fatigue, anemia, constipation, decrease in weight, asthenia, 
decreased appetite, and nausea.  The majority of these events were grade 1 or 2 and appeared to be 
related to the underlying CRC.  The prevalence of these events was similar in the bermekimab and 
placebo groups.  Two infusion reactions were reported in this trial, and they were not serious or 
severe (grade I or II). 
 
Bermekimab is a recombinant human IgG1 monoclonal antibody specific for human interleukin-
1α (IL-1α).  As such, it is an immunomodulator that has anti-inflammatory and anti-neoplastic 
properties.  Other agents that could be considered in the same pharmacologic class include biologic 
agents that target IL-1 receptor antagonist and IL-1 beta.  Potential risks for agents in this class 
include infusion or injection site reactions and risk of infection. 
 
Bermekimab is considered to be a True Human monoclonal antibody.  Unlike previous generations 
of humanized or fully human antibodies, the entire bermekimab heavy and light chain sequences 
are identical to those found in naturally-occurring human IgG1κ, with the light and heavy chain 
variable regions being identical to those originally expressed by a peripheral blood B lymphocyte 
that was obtained from a healthy individual.  No in vitro affinity maturation or modifications have 
been made to improve its natural binding affinity (211 +/- 31 pM).  We believe that a true human 


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antibody should be effectively non-immunogenic in humans and thus exhibit optimal activity and 
pharmacokinetics.  To date, no treatment emergent anti-drug antibodies specific to bermekimab 
have been identified. 
 
The mechanism behind infusion reactions is not clear in all cases.  It may involve a reaction against 
the antibody products themselves, or, against some minor residual component from the 
manufacturing process (i.e. host cell proteins).  To date, there has been a very low incidence of 
injection site or infusion reactions observed (20 patients out of 831 total; 2.4%).  All except two of 
these patients had grade 1 or 2 reactions that did not result in discontinuation.  In order to mitigate 
this class-specific risk, close monitoring is required during the bermekimab infusion and for at least 
1 hour after the end of the infusion.  Availability of resuscitation equipment must be ensured.  Pre-
medication with antihistamines or corticosteroids is not required. 
 
For the purposes of expedited safety reporting in clinical trials, the following should be 
considered expected events: 
 
• 
Infusion Related Reactions 
• 
Injection Site Reactions 
 
10.  STATISTICAL PLAN 
This section provides the basis for the statistical analysis plan (SAP) for the study. The SAP may 
be revised during the study to accommodate amendments to the clinical study protocol, and to make 
changes to adapt to unexpected issues in study execution and data that may affect planned analyses.  
Analysis variables are listed in Section 8. 
 
10.1 Statistical Hypothesis 
No formal hypothesis tests will be performed for the primary endpoints. 
 
10.2 Determination of Sample Size 
The sample size chosen was one of convenience, and no formal sample size calculations were 
performed. 
 


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10.3 Analysis Sets 
10.3.1 Safety Analysis Sets 
The safety analysis set (SAF) consists of all patients that receive at least one dose of study 
medication and will be analyzed as treated. 
 
The secondary endpoints will be analyzed based upon the SAF, as well as the per protocol 
population (PP).  The per protocol population will consist of those patients that complete both the 
baseline (visit 1) and visit 13 assessments of their hidradenitis (HISCR, PGA, Modified Sartorius, 
VAS, and DLQI). 
 
10.4 Patient Disposition 
A listing of all patients prematurely discontinued from the study, along with reasons for 
discontinuation will be provided. In addition, the total number of patients for each of the 
following categories will be summarized. 
• 
The total number of screened patients: met the inclusion criteria regarding the target 
indication and signed the informed consent 
• 
The total number of enrolled patients: met all inclusion/exclusion criteria and receive at 
least one dose of therapy 
• 
The analysis sets (SAF, PP) 
• 
The total number of patients who discontinued the study, and the reasons for 
discontinuation 
• 
A listing of patients prematurely discontinued from treatment, along with reasons for 
discontinuation 
 
10.5 Statistical Methods 
Continuous data will be summarized for each treatment group using the number of observations 
available (N), means, standard deviation (SD), minimums, medians, and maximums.  Categorical 
data will be summarized for each treatment group using counts and percentages.  Missing data will 
not be categorized in the summaries. 
10.5.1 Demography and Baseline Characteristics 
Demographic and baseline characteristics will be summarized descriptively by treatment group.  
Continuous variables will be summarized with mean, median, SD, minimum, and maximum.  
Categorical variables will be summarized with frequency and percentage. 


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10.5.2 Safety Analysis 
The primary objective of this study is to evaluate the safety and tolerability of 400mg dose of 
bermekimab. Safety endpoints will be evaluated by monitoring adverse events from clinical and 
laboratory reporting. The safety analysis will be based on the SAF population defined as all subject 
who received at least one dose of study medication. A summary of safety results will be presented 
for each treatment group. 
 
10.5.2.1 Analysis of Adverse Events 
Adverse events reported in this study will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) coding dictionary (version 21.0 or newer). Coding will be to lowest level 
terms. The verbatim text, the PT, and the primary SOC will be listed in patient listings.  
 
Pre-treatment AEs are defined as those that develop or worsen in severity from the time the patient 
provides informed consent, prior to the first dose of study drug.  Treatment emergent AEs (TEAEs) 
are defined as AEs that develop or worsen in severity following the first dose of study drug through 
the last study visit. 
 
TEAEs will be grouped by MedDRA System Organ Class (SOC) and Preferred Term (PT) within 
SOC and will be presented for each treatment group. The number and percent of subjects reporting 
at least one adverse event by PT will be summarized across groups A & B. The number and 
percentage of patients experiencing AEs and TEAEs will be summarized by seriousness (SAEs), 
severity (grades 1-5), SOC, and PT. 
 
10.5.2.2 Other Safety 
Vital Signs 
Summaries of vital sign parameters by treatment dose cohort will include: 
• 
Each vital sign parameter (blood pressure, pulse, oxygen saturation, respiratory rate and 
body temperature) and change from baseline 
• 
The number (n) and percentage (%) of patients with grade 2 or greater vital sign AEs 
• 
Listings will be provided with flags indicating the AE grade 
 
Laboratory Tests 


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Clinical laboratory values will be converted to standard international units. Clinical laboratory 
(hematology and chemistry) data will be listed for each subject. Laboratory data will be 
summarized by treatment group. Values outside the normal reference range will be flagged as high 
or low on the listings. Summaries of 
laboratory variables by treatment group will include: 
• 
Each laboratory result and change from baseline 
• 
The number (n) and percentage (%) of patients with grade 2 or greater laboratory AEs 
10.5.3 Analysis of Secondary Endpoints: 
Proportion of patients achieving a positive Hidradenitis Suppurativa Clinical Response (HiSCR) 
score after 13 weeks will be summarized by treatment group (and pooled overall population). The 
corresponding 95% confidence interval (CI) for the point estimate will be provided.  Subjects 
previously enrolled in the 200mg/weekly dosing cohort who have received two or fewer 
bermekimab injections (2 x 200mg doses) before beginning the 400mg weekly doses will be 
included for data analysis together with those receiving all doses at 400mg/weekly. Patients who 
have received more than 2 bermekimab injections of 200mg may enter the 400mg/week arm; 
however, only patients who have received two or fewer bermekimab injections will be included in 
the data analysis. 
 
Change in outcomes from baseline to week 13 (VAS for disease, VAS for pain, DLQI, 
inflammatory lesion count, PGA, Disease Activity Score, and modified Sartorius score) will be 
summarized using descriptive statistics (n, mean, standard deviation, median, minimum and 
maximum value). The 95% CI of the mean change from baseline will be provided.  
 
A rank-ordered analysis will be performed for the total abscess and inflammatory nodule count 
(ranked at 0, 1 or 2) and reduction in pain score (categorized as ≥30% reduction on pain score 
among patients with baseline score of ≥3). The change in modified Sartorius score will be 
dichotomized at 4 (≤4 least severe disease, higher indicates severe disease). Number and percent 
under each treatment group (and pooled overall) will be summarized. 
10.5.4 Pharmacodynamics (PK) analysis: 
Descriptive statistics of PK parameters will be presented in a table format. The summary will 
include average bermekimab concentration at visit cycles along with the standard deviation and 
coefficient of variation (CV). 


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10.5.5 Treatment Exposure 
The duration of exposure during the study will be presented by treatment and calculated as:   
(Date of last study drug injection – date of first study drug injection) + 7 
 
The number (%) of patients exposed to study drug will be presented by specific time periods for 
each treatment group. The time periods of interest will be specified in the SAP. 
 
In addition, duration of exposure during the study will be summarized for each treatment group 
using number of patients, means, SD, minimums, medians, and maximums. 
 
A summary of the number of doses, and dose volume by treatment arm will be provided. 
 
11.  STUDY MANAGEMENT AND ADMINISTRATION 
 
11.1 ETHICAL CONDUCT OF STUDY (GCP) 
The guidelines of the World Medical Association Declaration of Helsinki in its revised edition (48th 
General Assembly, Somerset West, Republic of South Africa, October 1996), the guidelines of ICH 
GCP (CPMP/ICH/135/95), as well as the demands of national drug and data protection laws and 
other applicable regulatory requirements, will be strictly followed.  Approval will be obtained from 
the appropriate regulatory authorities before sites are initiated.  
 
11.2 IRB AND ETHICS COMMITTEE APPROVAL  
Prior to initiation of the study, the protocol, the informed consent form, the subject information 
sheet(s), details of the subject recruitment procedures and any other relevant study documentation 
will be submitted to the responsible IRB or Ethics Committee (EC).  The Investigator will report 
promptly to the IRB/EC any new information that may adversely affect the safety of subjects or the 
conduct of the study. Similarly, the Investigator will submit written summaries of the study status 
to the IRB/EC annually, or more frequently if requested by the IRB/EC.  Upon completion of the 
study, the Investigator will provide the IRB/EC with a brief report of the outcome of the study, if 
required. 
 


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11.3 PROTOCOL MODIFICATIONS  
Modifications of the signed protocol are only possible by approved protocol amendments and with 
the agreement of all responsible persons.  The procedure for approval of a protocol amendment is 
identical to that for approval of the protocol.  The IRB/EC must be informed of all protocol 
amendments and should be asked for its opinion as to whether a full re-evaluation of the ethical 
aspects of the study is necessary by the committee.  This should be fully documented.  The 
Investigator must not implement any deviation from or change to the protocol, without discussion 
with an agreement by the study Sponsor and prior review and documented approval/favorable 
opinion of the amendment from the relevant IRB/EC, except where it is necessary to eliminate an 
immediate hazard to study subjects, or where the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in CRA(s), change of telephone number(s)). 
Protocol amendments will be submitted to the appropriate authority(ies) as required by the 
applicable regulatory requirement(s). 
 
11.4 SUBJECT INFORMATION AND CONSENT  
The Investigator is responsible for ensuring that no subject will receive any study-related 
examination or activity before that subject has given an IRB/EC approved informed consent.  The 
subject must give written consent after the receipt of detailed information.  The verbal explanation 
will cover all the elements specified in the written information provided for the subject.  The 
Investigator will inform the subject of the aims, methods, anticipated benefits and potential hazards 
of the study, including any discomfort it may entail.  The subject must be given every opportunity 
to clarify any points he/she does not understand and if necessary, ask for more information.  At the 
end of the interview, the subject may be given time to reflect if this is required, or if the subject 
requests more time.  Subjects and/or legal guardian forms will be kept and archived by the 
Investigator in the Investigator's study file.  It should be emphasized that the subject is at liberty to 
withdraw their consent to participate at any time, without penalty or loss of benefits to which the 
subject is otherwise entitled.  Subjects who refuse to give, or withdraw, written informed consent 
may not be included or continued in this study, but this will not impact their subsequent care.  The 
Investigator will notify in writing each subject’s primary care physician (or equivalent) of the 
subject’s intent to participate in the study. 
 
11.5 DATA PROTECTION AND CONFIDENTIALITY  
By signing the final protocol, every participating Investigator agrees to keep all information and 
results concerning the study and the investigational product confidential.  The confidentiality 


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obligation applies to all personnel involved at the investigational site.  The Investigator must ensure 
that each participant’s anonymity will be maintained in accordance with applicable laws. On eCRFs 
or other documents submitted to the Sponsor, subjects should not be identified by their name, but 
by subject ID number.  The Investigator should keep a separate log of ID numbers, names and 
addresses.  Documents that contain the names associated with these ID numbers (e.g., written 
consent/assent forms), are not for submission to the Sponsor and should be maintained by the 
Investigator in strict confidence except to the extent necessary to allow auditing by regulatory 
authorities, auditing or monitoring by the Institutional Review Board/EC, the Sponsor personnel or 
their affiliates and designees (such as CRAs).  
 
Copies of radiological scans and autopsy reports (and other documents), if applicable, that may be 
requested by the Sponsor should be de-identified.  The Investigator shall obtain all such permissions 
and authorizations as may be necessary or desirable to allow the collection and use of information 
protected under federal privacy laws and state privacy laws, including permission/authorization for 
monitoring and analysis (including re-analysis in combination with results of other studies), for 
regulatory submission purposes and for applicable reporting (if any) required to be made by 
Sponsor, its affiliates and their designee.  
 
11.6 STUDY REPORT AND PUBLICATIONS  
A final integrated clinical/statistical report will be prepared that is compliant with the ICH 
Harmonized Tripartite Guideline: Structure and Content of Clinical Study Reports 
(CPMP/ICH/137/95).  The results of this study will be published and/or presented at scientific 
meetings in a timely manner.  The publication policy is described in the contract between the 
Sponsor and Investigator.  
 
11.7 STUDY FILES AND RETENTION OF RECORDS  
Copies of all study documents should be retained by the Investigator until at least two years after 
the last approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed since the 
formal discontinuation of clinical development of the investigational product, in accordance with 
21 CFR 312.62.  These documents should be retained for a longer period however, if required by 
regulatory requirements or by agreement with the Sponsor.  It is the responsibility of the Sponsor 
to inform the Investigator/institution as to when these documents no longer need to be retained. 
The final database will be archived according to the regulatory requirements.  


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11.8 CASE REPORT FORMS  
Data for this protocol will be captured electronically in an Electronic Data Capture (EDC) system.  
Designated study personnel will be provided unique user names and passwords.  Each study 
personnel will have specific access within the electronic data collection system based on their role. 
The EDC system contains an audit trail associated with each individual's unique password that will 
document date and time of data entry and revisions.  All protocol-specified data is to be entered 
into the EDC system in a timely manner for review and audit by XBiotech.  All data is to be entered 
such that it will allow accurate interpretation and tabulation.  It is the Investigator's responsibility 
to ensure that all discontinued orders or changes in study or other medications entered into the 
database correspond to entries in the subject's medical records (i.e. source documents) and to 
acknowledge accurate completion of the eCRF. 
 
11.9 DRUG ACCOUNTABILITY  
A Drug Dispensing Log must be kept current and should contain the following information:  
• 
Initial inventory upon receipt of supplies at the study site  
• 
Identification number of each subject to whom test drug was administered  
• 
Date(s), quantities, lot numbers and calculations for all test drugs administered  
• 
Final inventory (upon completion of the study) 
 
This inventory must be available for inspection by the Clinical Research Associate.  The 
Investigator (or pharmacist, as appropriate) must maintain records of the delivery of the study 
medication to the study site, the inventory at the site, the usage for each subject, and destruction. 
The inventory must be available for monitoring, auditing or inspection.  A drug dispensing log must 
be kept current and should contain the following information:  
 
• 
The subject identification number to whom the drug is dispensed  
• 
The lot number of the drug dispensed  
• 
The date(s) and the quantity of the drug dispensed to the subject 
 
11.10   INSPECTIONS  
Investigator sites, the study database and study documentation may be subject to quality assurance 
audits during the course of the study either by the Sponsor or their appointed representatives.  In 
addition, regulatory bodies at their discretion may conduct inspections.  The Investigator shall 


XBIOTECH USA INC.                                                                                           PROTOCOL 2018-PT045 Version 3.1 
CONFIDENTIAL                                        30 August 2018                                            PAGE 49 of 50 
 
permit the authorized Sponsor, agents of the Sponsor, and regulatory agency employees to enter 
and inspect any site where the drug or records pertaining to the drug are held, and to inspect all 
records relating to an investigation, including subject records.  The Sponsor will not, however, copy 
any source data from the patient’s dossier.  Completed eCRFs must be made available by the 
Investigator for review by the Sponsor, agents of the Sponsor, the CRA and the regulatory agencies.  
To ensure the accuracy of data submitted, it is mandatory that representatives of the Sponsor and 
of the regulatory agencies have direct access to source documents (e.g., subject medical records, 
charts, laboratory reports, etc.).  Subject confidentiality will be protected at all times.  
 
11.11 ACCESS TO INFORMATION FOR MONITORING  
CRAs will establish and maintain regular contact between the Investigator and the Sponsor.  CRAs 
will evaluate the competence the study center, informing the Sponsor about any problems relating 
to facilities, technical equipment or medical staff. During the study, CRAs will check that written 
informed consent has been obtained from all subjects correctly and that data are recorded correctly 
and completely.  CRAs are also entitled to compare entries in eCRFs with corresponding source 
data and to inform the Investigator of any errors or omissions.  CRAs will also monitor adherence 
to the protocol at the Investigator site.  They will arrange for the supply of investigational product 
and ensure appropriate storage conditions are maintained. The CRA will make written reports to 
the Sponsor on each occasion when contact with the Investigator is made, regardless of whether it 
is by phone or in person.  During monitoring visits, entries in the eCRFs will be compared with the 
original source documents.  The Investigator must agree to meet with the CRA at regular intervals 
and to cooperate in resolving any queries or findings made during the monitoring process.  
 
11.12 STUDY DISCONTINUATION  
If the study is prematurely terminated or suspended, the Sponsor will promptly inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and the 
reason(s) for the termination or suspension.  The IRB/EC will also be promptly informed and 
provided with the reason(s) for the termination or suspension by the Sponsor or by the Investigator 
or/institution, as specified by the applicable regulatory requirement(s). 
 
 
 


XBIOTECH USA INC.                                                                                           PROTOCOL 2018-PT045 Version 3.1 
CONFIDENTIAL                                        30 August 2018                                            PAGE 50 of 50 
 
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