Clinical trial NCT02762994
Conditions: Psoriasis
Keywords: interleukin 17 monoclonal antibody psoriasis
Sponsor: Biocad
Start date: 2016-06-01; Completion date: 2017-05-01
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
BCD-085-2 is a next step in clinical investigation of BCD-085. BCD-085 is a monoclonal antibody to interleukin 17. During BCD-085-2 trial patients with moderate to severe plaque psoriasis, in whom poor response to previous treatment including UV-therapy and biologic drugs was registered, will receive 40, 80 or 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. Efficacy and safety parameters will be evaluated.

Detailed description:

Arms: arm 1: Patient will receive 40 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. arm 2: Patient will receive 80 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. arm 3: Patient will receive 120 mg of BCD-085 subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10. arm 4: Patient will receive placebo subcutaneously at weeks 0, 1, 2, 4, 6, 8, 10.
Interventions: intervention 1: BCD-085 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_001.pdf: 


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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ................................................................................................................ 2 
SIGNATURE PAGE ....................................................................................................................... 7 
ABBREVIATIONS ......................................................................................................................... 8 
TERMS AND DEFINITIONS ...................................................................................................... 11 
DOCUMENT HISTORY .............................................................................................................. 13 
Names/positions of investigators responsible for the study conduct. Contact information of the 
study sites ...................................................................................................................................... 13 
Name, job title, address and telephone number of the qualified physician responsible for taking 
medical decisions ........................................................................................................................... 15 
SYNOPSIS .................................................................................................................................... 16 
1. STUDY JUSTIFICATION ........................................................................................................ 31 
1.1. Introduction ......................................................................................................................... 31 
1.1.1. 
Overview of disease pathogenesis, epidemiology, and currently available 
treatment options ............................................................................................................... 31 
1.1.2. 
Background information for studied therapy ....................................................... 33 
1.2. Name and description of investigational products .............................................................. 34 
1.3. Relevant non-clinical and clinical aspects .......................................................................... 35 
1.3.1. Non-clinical studies ................................................................................................. 35 
1.3.2. Clinical trials ............................................................................................................ 49 
1.3.3. Conclusions and study rationale .............................................................................. 59 
1.4. Brief description of known and potential risks and benefit for study subjects (benefit/risk 
balance) ...................................................................................................................................... 60 
1.4.1. Benefit assessment ................................................................................................... 60 
1.4.2. Risk assessment ....................................................................................................... 60 
1.4.3. Conclusions .............................................................................................................. 61 
1.5. Description and justification of the route of administration, dosing regimen, and treatment 
course ......................................................................................................................................... 62 
1.5.1 Description and justification of the study design ..................................................... 62 
1.5.2. Description and justification of the route of administration, dosing regimen, and 
treatment course ................................................................................................................. 63 
1.5.3. Justification of placebo use ...................................................................................... 65 
1.6. Clinical study compliance with the regulatory requirements ............................................. 66 
1.7. Description of study population .......................................................................................... 66 
1.8. References ........................................................................................................................... 66 
2. STUDY PURPOSE AND OBJECTIVES ................................................................................. 69 


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2.1 Study aims ............................................................................................................................ 69 
2.2 Study objectives ................................................................................................................... 69 
3.0 HYPOTHESIS ......................................................................................................................... 70 
4. STUDY DESIGN ...................................................................................................................... 70 
4.1. Primary and secondary endpoints ....................................................................................... 70 
4.1.1 Primary endpoint ...................................................................................................... 70 
4.1.2 Secondary endpoints ................................................................................................. 70 
4.2. Description of the study type/design, study flow-chart, study procedures and periods ..... 71 
4.3. Measures to minimize/eliminate bias.................................................................................. 77 
4.3.1. Distribution of patients by study sites ..................................................................... 77 
4.3.2. Procedure of assigning study IDs ............................................................................ 77 
4.3.3. Stratification procedure ........................................................................................... 78 
4.3.4. Randomization procedure ........................................................................................ 82 
4.3.5. Blinding and subject-specific lots of investigational products ................................ 86 
4.4. Study therapy, doses, and dosage regimens of investigational products. Pharmaceutical 
form, packaging, and labeling of investigational products ........................................................ 86 
4.4.1. Study therapy, doses, and dosage regimens of investigational products ................. 86 
4.4.2. Pharmaceutical form, packaging, and labeling of investigational products ............ 87 
4.5. Expected duration of the study and subjects’ participation in the study ............................ 89 
4.6. Study periods ...................................................................................................................... 89 
4.6.1 Study schedule (visits and procedures) ..................................................................... 89 
4.6.2. Procedures by visits ................................................................................................. 93 
4.7. Description of individual study procedures ...................................................................... 100 
4.7.1. History taking, complaints, demographics ............................................................ 106 
4.7.2. Physical examination ............................................................................................. 107 
4.7.3. Vital signs .............................................................................................................. 108 
4.7.4. Laboratory tests ..................................................................................................... 108 
4.7.5. ECG ....................................................................................................................... 111 
4.7.6. Tuberculosis diagnostics ........................................................................................ 111 
4.7.7. Chest x-ray / fluorography ..................................................................................... 113 
4.7.8. PASI and BSA assessment .................................................................................... 114 
4.7.9. sPGA assessment ................................................................................................... 116 
4.7.10. Quality of life assessment .................................................................................... 117 
4.7.11. Psoriasis involvement of nails (NAPSI) .............................................................. 119 
4.7.12 Patient's assessment of pruritus ............................................................................ 120 
4.7.13 Assessment the injection pain ............................................................................... 121 
 
 
 
4.7.17 Procedures for storage and shipment of biosamples ............................................. 126 


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4.7.18. Total blood volume taken during the study ......................................................... 126 
 
4.7.20. Data entering to eCRF ......................................................................................... 129 
4.8. Stop rules and criteria for premature withdrawal for study subjects, study periods, and 
study as a whole ....................................................................................................................... 129 
4.8.1. Stop rules for study as a whole .............................................................................. 129 
4.8.2. Criteria for premature withdrawal of study subjects ............................................. 129 
4.9. Drug accountability ........................................................................................................... 130 
4.9.1. Handling of investigational products ..................................................................... 131 
4.10. Procedure for keeping and unblinding randomization codes .......................................... 132 
4.11. Data entered directly into CRF (i.e. no prior written or electronic record of data) and 
considered as source data ......................................................................................................... 132 
5. ELIGIBILITY AND EXCLUSION OF STUDY SUBJECTS ................................................ 133 
5.1. Inclusion criteria ............................................................................................................... 133 
5.2. Exclusion criteria .............................................................................................................. 134 
5.3. Withdrawal criteria ........................................................................................................... 137 
5.4. Follow-up of subjects withdrawn from the study or subjects who discontinued the study 
treatment but remain in the study for follow-up ...................................................................... 138 
5.4.1. Follow-up of patients who received at least one dose of BCD-085/placebo ......... 138 
5.4.2. Follow-up of subjects who did not receive a single dose of BCBD-085/placebo . 138 
6. TREATMENT OF STUDY SUBJECTS ................................................................................ 139 
6.1. Study therapy .................................................................................................................... 139 
6.1.1. Preparation of the investigational products for administration and administration 
procedure ......................................................................................................................... 140 
6.1.2. Adjustment and discontinuation of study therapy ................................................. 141 
6.1.3. Overdose ................................................................................................................ 141 
6.2. Concomitant therapy, medications allowed and prohibited by the Protocol .................... 141 
6.2.1. Allowed concomitant therapy ................................................................................ 141 
6.2.2. Prohibited concomitant therapy ............................................................................. 142 
6.3. Compliance with study procedures ................................................................................... 142 
6.3.1. Compliance assessment ......................................................................................... 143 
7. EFFICACY EVALUATION ................................................................................................... 143 
7.1 List of efficacy variables .................................................................................................... 143 
7.1.1. Definition of variables ........................................................................................... 143 
7.1.2. Efficacy endpoints ................................................................................................. 143 
7.1.3. Secondary endpoints .............................................................................................. 144 
7.2 Methods and timeframes for assessment, documenting, 
 
 ................................................................................................................................... 144 
7.2.1 Timeframes for analysis of efficacy variables ........................................................ 144 


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7.2.2 Methods and timeframes for assessment and documenting of efficacy variables .. 144 
8. SAFETY ASSESSMENT ....................................................................................................... 145 
8.1 List of safety endpoints ...................................................................................................... 145 
8.1.1 Definitions .............................................................................................................. 145 
8.1.2. Safety endpoints ..................................................................................................... 146 
8.2. Methods and timeframes for assessment, documenting and analysis of safety variables 147 
8.2.1. Timeframes for analysis of safety variables .......................................................... 147 
8.2.2. Methods and timeframes for assessment and documenting of safety variables .... 147 
8.3 Requirements for reports. Documenting and reporting AEs and completing AE Report 
Forms ....................................................................................................................................... 148 
8.3.1. Documenting AEs/SAEs ....................................................................................... 148 
8.3.2. AE/SAE reporting .................................................................................................. 148 
8.4. Methods and duration of follow-up of study subjects who had an AE/SAE .................... 151 
 
9. STATISTICS ........................................................................................................................... 153 
9.1. Description of statistical methods ..................................................................................... 153 
9.2. Statistical analysis steps and timelines for reports ............................................................ 154 
9.3. Planned number of subjects. Justification of sample size, including reasoning or 
calculations to justify statistical power and clinical justification of the study ........................ 155 
9.4. Suitable significance level ................................................................................................ 156 
9.5. Statistical criteria for study stopping/terminating the study ............................................. 156 
9.6. Handling of missing, unevaluable or uncertain data ......................................................... 156 
9.7. Reporting any deviations from the initial statistical plan ................................................. 157 
9.8. Selection of subjects for analysis ...................................................................................... 157 
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ................................................... 158 
11. QUALITY CONTROL AND QUALITY ASSURANCE .................................................... 158 
11.1. Data quality assurance .................................................................................................... 158 
11.2. Protocol compliance by investigator ............................................................................... 159 
11.3. Investigator’s responsibility to comply with the Protocol .............................................. 159 
11.4. Study monitoring ............................................................................................................ 160 
11.5. Data management and quality control ............................................................................ 160 
11.6. Study termination ............................................................................................................ 161 
12. ETHICS ................................................................................................................................. 161 
12.1. Ethical aspects of the study ............................................................................................. 161 
12.2. Confidentiality of study subjects .................................................................................... 162 
13. DATA HANDLING AND RECORD KEEPING ................................................................. 162 


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13.1. Record keeping at the study site ..................................................................................... 162 
13.2. Confidentiality of data .................................................................................................... 163 
13.3. Collection of data ............................................................................................................ 163 
14. REIMBURSEMENT AND INSURANCE ........................................................................... 164 
15. PUBLICATIONS .................................................................................................................. 165 
16. APPENDICES ....................................................................................................................... 167 
Appendix 1. SF-36 (Short Form Health Survey) ..................................................................... 167 
Appendix 2. Form for registration of injection site reactions. ................................................. 171 
 
 


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SIGNATURE PAGE 
To Protocol version 1.1 of July 12, 2016: An International Multicenter, Randomized, Double-blind, Placebo-
Controlled, Dose-finding Clinical Study of Efficacy and Safety of Subcutaneous BCD-085 in Patients with Moderate 
to Severe Plaque Psoriasis 
 
I, the undersigned, agree with the following: 
1. I have read the Protocol, I agree with all the provisions of the Protocol, and I will conduct the trial in 
compliance with the Protocol, and applicable regulatory requirements of the participating countries.  
2. I will ensure no deviations from the Protocol to take place without prior written agreement from the Sponsor 
and documented approval from local ethics committees of participating countries, except where necessary to 
eliminate an immediate hazard to the study participants. 
3. I confirm that all staff members are appropriately qualified to conduct the study, the study site has all 
necessary equipment, and I, the study investigator, have sufficient time to conduct this study in accordance 
with the Protocol 
4. I will take all due measures to ensure that all staff members involved in the study are informed about their 
obligations in accordance with this Protocol.  
5. I agree to fully cooperate with audits and inspections conducted in accordance with the rules established by 
the Sponsor and the state regulatory authorities. 
6. I understand that the text of this Protocol and all other materials and results of this study are confidential and 
proprietary to the Sponsor. I agree not to disclose any of this information to a third party unless required to 
do so by the law of the participating countries. 
Principal Investigator: 
 
______________________________ 
Signature 
______________________________   
Full Name 
______________________________   
Date 
 Vice President R&D, JSC BIOCAD 
______________________________ 
Signature 
______________________________   
Date 
 


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ABBREVIATIONS 
AE 
Adverse event 
AlkPh 
Alkaline phosphatase 
ALT 
Alanine transaminase  
APTT 
Activated partial thromboplastin time 
AST 
Aspartate transaminase 
 
 
 
 
BAbs 
Binding antibodies 
BCD-085 
A monoclonal anti-IL17 antibody manufactured by JSC BIOCAD 
BP 
Blood pressure 
BSA 
Body surface area affected by psoriasis 
CHF 
Congestive heart failure 
Cl 
Total clearance 
Cmax 
Maximum concentration 
CNS 
Central nervous system 
CRF 
Case Report Form 
CTCAE 
Common Toxicity Criteria for Adverse Events 
DNA 
Deoxyribonucleic acid 
ESR 
Erythrocyte sedimentation rate 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
HBcor 
Hepatitis B core antigen 
HBsAg 
Surface antigen of hepatitis B virus 
HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 


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HR 
Heart rate 
ICН 
International Conference on Harmonization 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IL 
Interleukin  
IMU 
Instruction for Medical Use 
INN 
International non-proprietary name 
IU 
International unit 
JSC 
Joint Stock Company 
LDH 
Lactate dehydrogenase  
MAb 
Monoclonal antibody 
MRT 
Mean residence time 
NAb 
Neutralizing antibodies 
NAPSI 
Nail Psoriasis Severity Index  
NYHA 
New York Heart Association 
PASI 
Psoriasis Area and Severity Index 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
POA 
Percentage of oval area  
RAMS 
Russian Academy of Medical Sciences 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SF-36 
Short Form Health Survey  
SOP 
Standard Operating Procedure 
sPGA 
Static Physicians Global Assessment 
SRI 
Scientific Research Institute 


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t½ 
Elimination half-life 
TNF-α 
Tumor necrosis factor alpha 
TO 
Thoracic organs 
VAS 
Visual analogue scale 
Vd 
Volume of distribution 
WHO 
World Healthcare Organization 










































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1. STUDY JUSTIFICATION 
1.1. Introduction 
1.1.1. Overview of disease pathogenesis, epidemiology, and currently available treatment 
options 
1.1.1.1.Epidemiology and significance of the disease 
Psoriasis is a common skin disease. In developed countries, up to 2% to 3% of the 
population has this disease. In Russia, about 100 000 new cases are registered per year, with the 
prevalence of psoriasis being about 1%. 
Clinical signs of psoriasis may differ by their severity, varying from mild forms 
manifesting as a few local lesions (rashes) on the skin to severe forms (about 30% of cases) 
affecting a significant percentage of the body surface. 
In the recent decades, severe therapy-resistant forms of psoriasis have become more 
common, which significantly affect the patients’ quality of life and lead, in some cases, to 
disability. This determines the social significance of psoriasis. According to Krueger et al., 
psoriasis, as a medical and social problem and a factor reducing the quality of life, shares the first 
place with depression, cardiovascular disorders, and diabetes. 
Today, psoriasis is considered incurable. However, modern treatment options are able to 
significantly improve the clinical course of the disease and make remissions longer. 
1.1.1.2.Current treatment options 
Psoriasis is commonly treated with topical agents such as glucocorticoids, calcipotriol, 
anthralin, coal tar extracts, etc. These treatment options are indicated in patients with mild 
psoriasis. 
Today, phototherapy is an important option in the treatment of psoriasis: 
photochemotherapy (PUVA) is a combination of the UVA light and a photosensitizing agent taken 
orally; selective phototherapy, which is a combination of middle- and long-wave UV light; and 
the narrowband UVB therapy. The light is likely to exert its therapeutic effects by stimulating the 
production of cytokines with immunosuppressive effects, enhancing the expression of several 
molecules on the cell surface, and inducing apoptosis. 


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Retinoids (synthetic derivatives of vitamin A) have been used in psoriasis for more than 25 
years. Retinoids inhibit the proliferation of epidermis, normalize keratinization, exert 
immunomodulating effects on dermal cells, and stabilize membrane structures of cells. 
In the recent decades, opinions about mechanisms of psoriasis have changed, and now it is 
considered a systemic autoimmune disease. Thus, approaches to its therapy have been revised as 
well. Cytostatic agents (methotrexate), systemic glucocorticoids, and cyclosporine for the 
treatment of moderate to severe psoriasis are taking a backseat to agents that are more selective. 
Biological medicinal products became a major achievement in the treatment of patients 
with psoriasis. Introducing the biologics into clinical practice was a breakthrough in the therapy 
of this disease and changed the world opinion about its potential outcomes. All biologics approved 
for the treatment of psoriasis show high effectiveness as compared to conventional medications. 
Due to their high specificity, monoclonal antibodies are low-toxic and produce minimum adverse 
effects. 
Biologics used in clinical practice can be classified as follows [1]: 
• Modulators of T-cells (alefacept) 
• Ihibitors of timor necrosis factor alpha (adalimumab, certolizumab, etanercept, 
golimumab, and infliximab) 
• Inhibitors of interleukins 12 and 23 (ustekinumab). 
The first biologics approved by the FDA for the treatment of psoriasis were alefacept (anti-
CD2) and efalizumab (anti-CD11). Efalizumab was also approved by the EMA. In 2009, 
efalizumab was recalled from the market following several cases of multifocal 
leukoencephalopathy reported with a long-term use of the drug. 
TNF-α inhibitors are monoclonal antibodies that with high affinity and specificity bind to 
the TNF-α thus preventing it from interaction with the receptors and inducing the lysis of TNF-α 
expressing cells in the presence of the complement. Today, these products are well investigated 
and have firmly established themselves as treatments for psoriasis. 
Another MAb commonly used in psoriasis is ustekinumab, which has a different 
mechanism of action. Ustekinumab contains fully human MAbs to the p-40 subunit of both IL-12 
and IL-23. These cytokines play a key role in the pathogenesis of inflammation mediated by the 
T-helper cells 1 and 17 [1]. 
Thus, psoriasis is a common and socially significant disease. The most effective treatments 
for psoriasis are biologics that affect various components of the disease. The recent findings 
suggest that interleukin-17 pays a key role in the development of psoriasis. Several drugs blocking 


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this cytokine demonstrated high efficacy and favorable safety in a number of clinical studies. Thus, 
development of drugs that block IL-17 signaling is a promising approach in searching new highly 
effective and safe treatments for psoriasis. 
1.1.2. Background information for studied therapy 
[10].  
[26, 27, 28], 
 
, 24, 25], 
[11, 12, 13, 14]. 


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1.2. Name and description of investigational products 
Investigational products in this study include BCD-085 (test drug) and placebo. 
Test drug: 
Invented name: N/A 
Internal code: BCD-085 
Chemical name: anti-IL-17 monoclonal antibody 
BCD-085, a therapeutic monoclonal antibody selective for interleukin-17, which has been 
developed by JSC BIOCAD, is an innovative biotechnology product. Its physicochemical, 
biological, and toxicological properties have been characterized in a number of non-clinical 
studies. 
BCD-085 
has 
been 
shown 
to 
bind 
interleukin-17 
with 
the 
affinity 
Phase I clinical study in healthy 
volunteers assessed the pharmacokinetics of BCD-085 and confirmed its safety upon a single SC 


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injection of ascending doses (refer to section 1.3.2), proving the feasibility of its further clinical 
investigation.  
If the clinical development is successful, implementation of a Russian innovative 
monoclonal anti-IL-17 antibody into clinical practice will improve the therapy of a wide range of 
autoimmune disorders and other chronic inflammatory diseases. 
1.3. Relevant non-clinical and clinical aspects 
1.3.1. Non-clinical studies 
1.3.1.1. Study of physicochemical properties and potency 
Physicochemical studies have shown that BCD-085 possesses the following 
characteristics: 
✓ The anti-IL-17 monoclonal antibody in BCD-085 binds human interleukin-17 
with affinity 
✓ The anti-IL-17 monoclonal antibody selectively blocks the production 
✓ The purity characteristics of the anti-IL-17 monoclonal antibody allow using it as 
a study drug in clinical studies in humans. 
1.3.1.2. Non-clinical pharmacodynamics 
1.3.1.2.1. Investigation of BCD-085 potency in the model autoimmune encephalitis 










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The inflammatory reaction evaluated by the involved joint surface was the most severe in 
animals from the placebo group (controls). In all groups that received BCD-085, the percentage of 
the involved joint surface was lower than that in the controls at all time points. The most 


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1.3.1.2.3. Repeated-dose immunogenicity study of BCD-085 
Immunogenicity of BCD-085 was studied in healthy cynomolgus monkeys (Macaca 
fascicularis) after multiple SC injections at a dose of 
 The drug was injected 
twice within 1 month followed by a 2-week recovery period. In parallel with the BCD-085 
concentration assay, blood samples were drawn for immunogenicity testing. 
Analysis of the presence/absence of binding anti-BCD-085 antibodies (the number of 
animals positive for binding antibodies) and the titer of binding antibodies upon repeated (given 
twice) SC injections has demonstrated that animals did not develop immunoglobulins binding 
BCD-085. The concentration of anti-BCD-085 antibodies was below the lower limit of detection. 
Thus, all animals were considered negative for binding anti-BCD-085 antibodies. Based on the 
experimental findings, we can conclude that BCD-085 is non-immunogenic when used according 
to the studied regimen. 
The study has shown that two SC injections of 
 BCD-085 are non-immunogenic 
in cynomolgus monkeys (do not result in accumulation of anti-BCD-085 binding antibodies).  
1.3.1.2.4. Single-dose toxicity of BCD-085 
The single-dose toxicity of SC anti-IL-17 monoclonal antibody (BCD-085) was studied at 
doses: 
. The minimum dose used in this study is equivalent 
to the expected therapeutic dose in humans with an account of the interspecies dose conversion 
factor. The medium dose was equivalent to 5 expected therapeutic doses. The maximum dose was 
equivalent to 10 expected therapeutic doses. 
The study used 16 male and female monkeys (Macaca fascicularis) with body weight from 
3.0 kg to 7.0 kg: 
1. BCD-085 
 (2 males and 2 females) 
2. BCD-085 
 (2 males and 2 females) 
3. BCD-085 
 (2 males and 2 females) 
4. Control (placebo): 2 females and 2 males. 
No animals died during the experiment and no animals developed any clinical signs of 
toxicity. No animals had any of the following: 
• Changes in appetite 
• Altered breathing pattern 
• Changes in stool 


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• Changes in vegetative reactions (pupil diameter, eye slit size, salivation, involuntary 
defecation, urination, increased diuresis) were observed 
• Effects on the pelage (piloerection, alopecia, pelage color) 
• Eye changes (tearing, discharge) 
• Effects on animal behavior. 
The study results showed that BCD-085 in the tested doses does not cause animal death or 
clinical signs of toxicity. It was technically impossible to inject the doses needed to assess the 
lethal dose (due to the limitations on the volume that can be injected). The general health of animals 
was satisfactory throughout the entire experiment; no body weight loss was registered. CBC 
parameters and blood biochemistry markers of the liver and urinary system health did not change 
during the observation period and were within the normal ranges. 
 
Some decrease in the serum glucose level was observed with the medium 
 and 
maximum 
 doses of BCD-085. This trend was observed on Day 7 and reached its 
maximum on Day 14 of the experiment (end of the experiment). At the end of the experiment, the 
serum glucose in animals dosed with 
 and 
 BCD-085 reached the lower level 
of normal. These findings suggest that the treatment with BCD-085 may be associated with 
disturbances of carbohydrate metabolism. 
 
1.3.1.2.5. Repeated-dose toxicity of BCD-085 
Repeated-dose toxicity was investigated in 18 monkeys (Macaca fascicularis). Three 
doses of BCD-085 were used: the maximum dose was two-fold higher than the MTD (determined 
in the single-dose toxicity study) - 
. 
Animals were distributed into 4 groups (by investigational product and its dose): 
Group 1 - BCD-085 
 (2 females and 2 males). 
Group 2 - BCD-085 
 (2 females and 2 males). 
Group 3 - BCD-085 
 (3 females and 3 males). 
Group 4 - placebo controls (2 females and 2 males). 
The study drug was administered as SC injections of the freshly prepared solution in 0.9% 
sodium chloride. The drug was administered once a week for 4 weeks. 
No deaths were recorded throughout the study. No clinical signs of toxicity were seen upon 
repeated injections of 
 BCD-085: 
• 
No changes in the appetite 
• 
No altered breathing pattern 


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• 
No stool changes 
• 
No changes in autonomic reactions (pupil diameter, eye slit size, salivation, 
involuntary defecation, urination, increased diuresis 
• 
No changes of the pelage (piloerection, alopecia, pelage color) 
• 
No eye changes (tearing, discharge) 
• 
And no changes in the behavior of cynomolgus monkeys. 
The test animals tolerated the drug well. They developed no clinical signs of toxicity, no 
motor or behavioral disturbances, no thermogenic reactions, and no changes were observed in how 
animals interacted with investigators. These findings were true for all tested doses and did not 
depend on the gender of animals. In this experiment, 
 BCD-085 did not 
affect the body weight of the monkeys. Multiple (once weekly for 4 weeks) SC injections of BCD-
085 at the highest dose 
 was associated with e tendency towards decreased body 
weight of cynomolgus monkeys. By the end of the drug-free recovery period, the body weight was 
back to baseline values.  
Repeated SC injections of the medium 
 and maximum 
 doses did 
not affect the CBC parameters assessed in this study. Injections of 
 BCD-085 were 
associated with a reversible increase in the ESR observed at the end of the injection period (Week 
4). 
The therapeutic anti-IL-17 monoclonal antibody (JSC BIOCAD) in all tested doses did not 
affect the hemostasis, protein synthetic function of the liver, and lipid metabolism; it does not 
elevate concentrations of enzymes specific for liver damage. It has been shown that repeated 
administration of 
 BCD-085 to Macaca fascicularis decreases the serum glucose level; 
therefore, the drug potentially can affect the carbohydrate metabolism. 
In this experiment, no drug effects were observed on the CNS, bioelectric activity of the 
heart, or urinary function (regardless of the dose). 
In non-clinical investigations, animals tolerated BCD-085 well. The drug did not alter the 
cardiovascular and urinary function and did not produce any local irritative effects. The drug is 
considered low-toxic and can be recommended for clinical development. 
1.3.1.2.5. Local tolerance studied as part of the BCD-085 repeated-dose toxicity 
Local tolerance was evaluated by external examination and histological findings. Tissues 
at the injection site and regional lymph nodes were taken for histology. 


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The study results prove that BCD-085 (JSC BIOCAD) exerts no local irritative effect when 
injected subcutaneously. Histologic studies did not show any changes in the injection sites or 
draining lymph nodes. 
1.3.1.2.6. Immunotoxicity of BCD-085 
Immunotoxicity upon multiple SC injections of BCD-085 was studied for the following 
doses: 
. The experiment was conducted in 9 male monkeys (Macaca 
fascicularis) of 3.0 kg to 7.0 kg. Animals were divided into three groups depending on the 
dose/drug administered: 
1. BCD-085 
 (3 males) 
2. BCD-085 
 (3 males) 
3. Placebo controls (3 males). 
The assessment of the lymphocyte phenotypes in the peripheral blood of primates upon 
repeated injections of BCD-085 has shown that the test drug does not alter the subpopulation ratio. 
Assessment of drug effects on humoral immunity is one of the main parts of 
immunotoxicity study. 
The obtained results evidence that repeated SC administration of BCD-085 does not alter 
the levels and balance of immunoglobulins M, G, A, and E. 
No changes in the phagocytic activity were observed during the study. Its intensity was 
similar in animals dosed with BCD-085 and controls. 
No significant changes in the intensity of lymphocyte proliferation were observed 
throughout the experiment, regardless of the BCD-085 dose. Proliferation activity in the groups of 
primates treated with BCD-085 was similar to that in the placebo controls. 
Experimental findings suggest that repeated administration of BCD-085 was not associated 
with significant changes in any variables assessed in this study. Thus, it was considered that 
multiple SC administration of 
 BCD-085 in cynomolgus monkeys 
produces no immunotoxicity in the said experimental settings. 


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1.3.1.2.8. Allergy-inducing potential of BCD-085 
Therefore, BCD-085 did not have any allergenic potential. These results confirm the 
feasibility of using BCD-085 in clinical development. 


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1.3.1.2.10. Cross-reactivity of BCD-085 
The study aimed at evaluating the cross-reactivity of BCD-085 by immunohistochemical 
(IHC) staining in frozen normal human tissues. 
The frozen normal human tissues consisted of autopsy material. Thirty-three types of human 
tissue were used for analysis, 
 
 


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1.3.2. Clinical trials 
By the time this Protocol was written, phase I clinical study was completed that 
investigated the safety, tolerability, and pharmacokinetics of single ascending doses of BCD-085. 
Results of this study are described below. 
1.3.2.1. Comparative single-dose study of pharmacokinetics, safety, and tolerability   
When this Protocol was prepared, an open-label clinical study of the pharmacokinetics, 
tolerability, and safety of single ascending doses of BCD-085 in healthy volunteers was completed. 
This study demonstrated a favorable safety profile of the drug and allowed characterizing the 
pharmacokinetics of BCD-085. 
According to the approved protocol, this clinical study of the safety, tolerability, and PK 
of single ascending doses of BCD-085 had to include 8 cohorts of healthy male volunteers. 
Participants were included in the study as follows: 
1.  
Cohort 1: 1 volunteer who received a single SC injection of BCD-085 at a dose of 
0.05 mg/kg of body weight. 
2. 
Cohort 02: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 0.05 mg/kg of body weight. 


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3. 
Cohort 03: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 0.25 mg/kg of body weight. 
4. 
Cohort 04: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 0.825 mg/kg of body weight. 
5. 
Cohort 05: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 1.25 mg/kg of body weight. 
6. 
Cohort 06: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 1.75 mg/kg of body weight. 
7. 
Cohort 07: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 2.25 mg/kg of body weight. 
8. 
Cohort 08: 3 volunteers who received a single SC injection of BCD-085 at a dose 
of 3.00 mg/kg of body weight. 
Volunteers were included in the study one after another. At first, 1 volunteer was included 
in Cohort 01 and receives a single subcutaneous injection of BCD-085 at a dose of 0.05 mg/kg 
(estimated starting safe dose). If the patient had no grade 3/4 toxicity events related to the drug 
within the first 7 days after the injection, 3 more volunteers were included in Cohort 02, etc.   
No events of dose-limiting toxicity (DLTs) were observed, and 22 male volunteers were 
included in the study. Each participant had a verified diagnosis “healthy” according to the results 
of the standard clinical, laboratory, and instrumental examinations. 
The study drug was well tolerated. Most adverse events were laboratory abnormalities (of 
blood hematology and biochemistry), of grade 1 severity, and, according to investigators, possibly 
related to the study therapy. No injection site reactions were reported. No dose-limiting toxicity 
was reported. 
Hepatobiliary disorders were the most common AEs. They included elevated AST (1 event 
in cohorts 05 and 06) and elevated ALT (1 event in cohorts 01 and 05), which were recorded in 
9.09% of subjects. Blood and lymphatic system disorders were reported less frequently and were 
represented by 1 case of neutropenia in Cohort 05 (4.54%). The overall number of AEs was 6 
(27.27%), including 5 (22.73%) that did not meet the seriousness criteria. All AEs (except for 
SAEs) were of severity grade 1 and considered related to the study treatment. The investigators 
judged the causality as possible. 
One SAE was reported in the study – a closed head injury (concussion of the brain) that 
occurred in a road accident. The SAE was not related to the study drug. The investigator qualified 
this SAE as grade 3. 






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1.3.2.2. Efficacy and safety findings 
The efficacy of BCD-085 in patients has not yet been investigated. Today, information is 
available on the efficacy of the closest analogs of BCD-085 that have the similar mechanism of 
action (ixekizumab, secukinumab, and brodalumab). The first 2 products contain fully human 
monoclonal antibodies selective for interleukin-17, and the last one contains antibodies that target 
the IL-17 receptor. 
Phase II clinical study of ixekizumab includes 142 patients with moderate to severe 
psoriasis. The patients are randomized to 5 arms: 150 mg, 75 mg, 25 mg, and 10 mg of ixekizumab, 
and placebo. BCD-085/placebo was administered at weeks 0, 2, 4, 8, 12 and 16. The primary 
endpoint set as the proportion of patients who achieved a PASI75 at Week 12 of therapy was 
82.1%, 82.8%, 76.7%, 29.0%, and 7.7%, respectively. The differences with the placebo arm were 
significant for all doses except for the 10 mg dose. In the 25 mg arm, no significant differences 
with the placebo arm were observed in the proportion of PASI 100 responders. The differences 
between the arms given 75 mg and 150 mg ixekizumab were not significant. The drug 
demonstrated a favorable safety profile at all doses. Adverse events included nasopharyngitis, 
upper respiratory tract infections, administration site reactions, and headache. The frequency of 
these adverse events did not exceed that in the placebo arm [15]. 
Results from two phase III clinical studies, UNCOVER-2 and UNCOVER-3, are expected 
to gain approval for ixekizumab [16]. These studies involved patients with moderate to severe 
plaque psoriasis ((BSA ≥ 10%, sPGA≥ 3, and PASI ≥ 12). Patients (n = 2570) were randomly 
assigned 1:2:2:2 to receive placebo, etanercept (50 mg twice a week), ixekizumab 80 mg every 2 
weeks  after the starting dose of 160 mg [IX2W arm] or ixekizumab 80 mg every 4 weeks after 
 
14Genovese M.C. et al. LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of 
patients with rheumatoid arthritis. A phase I randomized, double-blind, placebo-controlled, proof-of-concept study. // 
Arthritis and rheumatism. Vol.62, No.4, April 2010, pp.929-939. 


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the starting dose of 160 mg [IX4W arm]. The UNCOVER-2 study involved 1224 patients and 
UNCOVER-3 study involved 1346 patients. 
At week 12, both primary endpoints (PASI 75 response and sPGA scores of 0/1 at Week 
12.) were met in both studies. In the UNCOVER-2 and UNCOVER-3 trials, the PASI75 was 
achieved in 89.7% and 87.3% of patients, respectively (IX2W arm), in 77.5% and 84.2% of 
patients (IX4W arm), 2.4% and 7.3% of patients (placebo arm), and 41.6% and 53.4% of patients 
(etanercept arm). The sPGA response was achieved in 83.2% and 80.5% of patients, respectively 
(IX2W),  72.9% and 75.4% of patients (IX4W), 2.4% and 6.7% of patients (placebo arm), and 
36.0% and 41.6% of patients (etanercept arm). 
Serious adverse events were registered in 1.9% of patients in the IX2W arm, 1.9% of 
patients in the IX4W arm, 1.9% of patients in the placebo arm, and 1.8% of patients in the 
etanercept arm. No deaths occurred in this study. The most frequently observed AEs are listed in 
Table 5. 
 
Table 5. Adverse reactions from the UNCOVER-2 and UNCOVER-3 trials. 
Adverse reaction 
Placebo, 
n=360 
Etanercept, 
n=739 
IX4W 
n=729 
IX2W 
n=734 
Any treatment-emergent AE 
44.2% 
53.9% 
57.5% 
57.4% 
SAEs 
1.9% 
1.8% 
1.9% 
1.9% 
Any infection 
20.3% 
21.2% 
25.8% 
25.3% 
Nasopharyngitis 
7.8% 
7.4% 
3.8% 
8.3% 
Upper respiratory tract infection 
3.3% 
4.6% 
3.3% 
3.7% 
Injection-site reaction 
1.1% 
10.8% 
8.5% 
10.4% 
Injection-site erythema 
0.6% 
3.9% 
1.9% 
3.3% 
Injection-site pain 
1.4% 
1.2% 
1.2% 
2.9% 
Pruritus 
1.4% 
1.1% 
2.2% 
1.9% 
Headache 
2.2% 
4.2% 
4.7% 
4.5% 
Arthralgia 
2.2% 
2.3% 
2.5% 
2.7% 
 
Brodalumab is an antibody targeting the receptor that binds to interleukin 17A, interleukin 
17F, and the heterodimeric IL-17A/F cytokine. In phase II study [17], brodalumab was given at a 
dose of 280 mg once a month or at a dose of 70, 140, or 210 mg at weeks 0, 1, 2, 4, 6, 8, and 10. 
The 75% PASI improvement at Week 12 was observed in 67%, 33%, 77%, and 82% of patients 


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given brodalumab, respectively. In the placebo arm, no PASI75 response was observed at all. The 
frequency of PASI75 response in all brodalumab arms differed significantly from that in the 
placebo arm. Adverse events were rare. The rate of AEs was slightly higher in the high-dose arms. 
Two SAEs were registered in the study (grade 3 neutropenia). 
The main pivotal phase III studies with brodalumab are the AMAGINE-2 and AMAGINE-
3 [18]. Patients with moderate to severe psoriasis were randomly assigned to 4 arms. Patients in 
Arm 1 were given 210 mg of brodalumab every 2 weeks; patients in Arm 2 - 140  mg of 
brodalumab every 2 weeks; patients in Arm 3 were given ustekinumab (45 mg for patients under 
100 kg and 90 mg for patients ≥ 100 kg); and patients in Arm 4 were given placebo. At Week 12, 
patients given brodalumab were re-randomized to different drug doses: 210 mg every 2 weeks, 
140 mg every 2 weeks, 140 mg every 4 weeks, and 140 mg every 8 weeks. Patients given 
ustekinumab continued receiving the treatment every 12 weeks, and patients from the placebo arm 
were given brodalumab 210 mg every 2 weeks. The endpoints were set as the proportion of patients 
who achieved a PASI75 at Week 12 and the proportion of patients who had the sPGA score 
decreased from baseline to 0/1. Two studies randomized 1831 patients; 1776 patients completed 
12 weeks of treatment, and 1691 patients completed 52 weeks of treatment. 
Study results are presented in Table 6. Brodalumab 210 mg given every 2 weeks was 
superior to ustekinumab with respect to the proportion of PASI75 responders and sPGA 
responders. 
 
Table 6. Results from the AMAGINE-2 and AMAGINE-3 trials at Week 12 of treatment. 
Outcome 
Placebo, 
n=624 
Ustekinumab, 
n=613 
Brodalumab, 
140 mg every 2 
weeks, 
n=1239 
Brodalumab, 210 
mg every 2 weeks, 
n=1236 
PASI75 response 
7.1% 
69.7% 
67.9% 
85.7% 
sPGA response 
4.0% 
59.1% 
59.0% 
79.1% 
 
Most of the patients retained the PASI75 and sPGA response at Week 52. The proportion 
of patients with an sPGA score of 0 or 1 at Week 52 was significantly higher among those who 
had received 210 mg or 140 mg of brodalumab every 2 weeks than among those who had received 
the other brodalumab maintenance regimens. 


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The main adverse reactions registered in the AMAGINE-2 and AMAGINE-3 trials during 
the induction phase (first 12 weeks) are listed in Table 7. 
 
Table 7. Adverse reactions registered in the AMAGINE-2 and AMAGINE-3 trials during the 
induction phase (first 12 weeks). 
Adverse reaction 
Placebo, 
n=624 
Ustekinumab, 
n=613 
Brodalumab, 
140 
mg 
every 
2 
weeks, 
n=1239 
Brodalumab, 
210 
mg 
every 
2 
weeks, 
n=1236 
Any AEs 
51.0% 
56.3% 
56.3% 
57.3% 
SAEs 
1.8% 
1.0% 
1.9% 
1.2% 
Death 
0.0% 
0.0% 
0.0% 
0.1% 
Nasopharyngitis 
5.8% 
5.5% 
6.6% 
6.2% 
Upper respiratory tract infection 
6.4% 
5.9% 
4.0% 
5.1% 
Headache 
3.7% 
3.8% 
5.4% 
4.2% 
Arthralgia 
5.1% 
2.4% 
4.7% 
5.2% 
Injection site reaction 
1.4% 
2.0% 
1.6% 
1.5% 
 
In November 2014, Amgen and AstraZeneca announce positive results from a phase III 
trial, according to which brodalumab was shown superior to ustekinumab and placebo. 
Secukinumab is a monoclonal antibody targeting interleukin-17. In January 2015, the U.S. 
FDA approved secukinumab for the treatment of moderate to severe plaque psoriasis. 
A phase II study [19] involved 125 patients with moderate to severe plaque psoriasis. These 
patients were given placebo or a single injection of 25 mg secukinumab, or 25 mg, 75 mg or 150 
mg of secukinumab every month. The PASI75 at week 12 was set as the primary endpoint, which 
was achieved in 9% of patients given placebo, 4% of patients given a single 25 mg dose of 
secukinumab, and in 18%, 57.1%, and 81.5% of patients given 25 mg, 75 mg, and 150 mg of 
secukinumab once a month. The drug showed a favorable safety profile. The most common AEs 
were a progression of the main disease, nasopharyngitis, and upper respiratory tract infections. 
Another phase II study [20] used multiple dosing regimens in 404 patients. As an induction 
therapy, the patients were given a single dose of secukinumab (Week 0) or secukinumab weekly 
injections (weeks 0, 1, 2, 4, and 8). As a maintenance treatment (weeks 12-36), the patients were 


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given either injections at weeks 12 and 24 (“fixed interval” regimen) or injections on an on demand 
basis (“start of relapse” regimen). During the induction phase, the proportion of PASI75 
responders was higher in the arms given secukinumab every month or more frequently as 
compared to the placebo arm (54.5% and 42.0% vs.  1.5%). In the maintenance phase, the number 
of patients was assessed who achieved a PASI75 at least once from Week 20 to Week 28. The 
regular dosing regimen was shown beneficial. (84.6% vs. 67.2%). The most frequently observed 
AEs were disease progression, nasopharyngitis, and headache. 
Secukinumab was approved on the basis of the findings from two pivotal phase III studies: 
ERASURE and FIXTURE [21]. These studies involved patients with moderate to severe plaque 
psoriasis, PASI score of 12 or higher and IGA mod of 3 or 4, and a total BSA of minimally 10%.  
Patients in the ERASURE  study were randomly assigned to 3 arms: secukinumab 300 mg, 
secukinumab 150 mg, or placebo. Patients in the FIXTURE study were randomized to 4 arms: 
secukinumab 300 mg, secukinumab 150 mg, etanercept, or placebo. 
Patients from secukinumab arms were given the drug at weeks 0, 1, 2, 3, and 4, and then 
every 4 weeks for 48 weeks. Patients from the etanercept arm were given 2 injections twice a week 
until Week 12 and then once weekly up to Week 51. 
Study results are presented in Tables 8 and 9. 
 
Table 8. Results from the ERASURE study at Week 12 of treatment. 
Outcome 
Placebo, 
n=246 
Secukinumab 
300 mg 
n=245 
Secukinumab 
150 mg 
n=243 
PASI75 response 
4.5% 
81.6% 
71.6% 
sPGA response 
2.4% 
65.3% 
51.2% 
 
Table 9. Results from the FIXTURE study at Week 12 of treatment. 
Outcome 
Placebo, 
n=246 
Secukinumab 
300 mg 
n=245 
Secukinumab 
150 mg 
n=243 
Etanercept, 
n=323 
PASI75 response 
4.5% 
77.1% 
67.0% 
44.0% 
sPGA response 
2.8% 
62.5% 
51.1% 
27.2% 
 


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In the ERASURE study, the number of patients who had at least one AE was higher in 
secukinumab arms than in the placebo arm (55.1% in the 300 mg arm, 60.4% in the 150 mg arm, 
and 47% in the placebo arm). Infections and infestations were significantly more frequent with 
secukinumab than with placebo (29.4%, 26.9%, and 16.2%, respectively). The most common AEs 
were nasopharyngitis, headache, and upper respiratory tract infections. 
In the FIXTURE study, the safety parameters were similar between secukinumab and 
etanercept. Injection site reactions were rarer in secukinumab arms (0.7% vs. 11.1%). The 
incidence of adverse events is presented in Table 10. 
 
Table 10. Adverse reactions in the FIXTURE study during the induction phase (first 12 weeks). 
Adverse reaction 
Placebo, 
n=246 
Secukinumab 
300 mg 
n=245 
Secukinumab 
150 mg 
n=243 
Etanercept, 
n=323 
Any AEs 
49.8% 
55.5% 
58.4% 
57.6% 
SAEs 
1.8% 
1.2% 
2.1% 
0.9% 
Nasopharyngitis 
8.0% 
10.7% 
13.8% 
11.1% 
Upper respiratory tract infection 6.4% 
5.9% 
4.0% 
5.1% 
Headache 
7.0% 
9.2% 
4.9% 
7.1% 
Diarrhea 
1.8% 
5.2% 
3.7% 
3.4% 
Pruritus 
3.4% 
2.5% 
3.7% 
2.5% 
Arthralgia 
3.1% 
1.5% 
4.3% 
3.7% 
Upper respiratory tract infection 0.9% 
2.1% 
3.1% 
2.2% 
Back pain 
1.8% 
2.5% 
2.4% 
2.8% 
Cough 
1.2% 
3.4% 
1.5% 
1.2% 
Arterial hypertension 
1.2% 
1.5% 
3.1% 
1.5% 
Nausea 
2.1% 
2.5% 
1.8% 
1.2% 
Pain in the mouth or throat 
2.1% 
2.8% 
1.5% 
1.2% 
 
Thus, all three products blocking the signaling of interleukin-17 demonstrated high efficacy 
and favorable safety in clinical trials. 


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1.3.3. Conclusions and study rationale 
Psoriasis is a common skin disease. In Russia, about 100 000 new cases of psoriasis are 
registered every year. Despite a significant progress in the development of treatment options, 
severe atypical forms resistant to therapy have become more common in the last decade. Biologics 
containing monoclonal antibodies are considered the most effective agents to treat these forms of 
psoriasis.  
The current knowledge about the mechanisms of psoriasis indicates the crucial role of 
interleukin-17 in the skin damage. Considering this information, a number of monoclonal antibody 
drugs have been developed selectively targeting either interleukin-17 or its receptor. The high 
efficacy and favorable safety profiles of the new biologics were confirmed in a number of clinical 
studies. 
JSC BIOCAD has developed an original monoclonal anti-IL-17 antibody (BCD-085), which 
The physicochemical studies of BCD-085 have characterized its primary, secondary, and 
tertiary structure, glycosylation pattern, purity and homogeneity, and in vitro binding to the antigen 
the suppression of inflammation. The drug was well tolerated by experimental animals and was 
considered low-toxic. Experiments were also conducted to characterize the pharmacokinetics of 
the drug. 
Results obtained in a comprehensive non-clinical program allowed conducting phase I 
clinical study in healthy volunteers. This study confirmed the previously discovered 
characteristics: low toxicity and good tolerability of the drug. Pharmacokinetics of BCD-085 
demonstrated in this study was typical for monoclonal antibodies. The drug has a long elimination 
half-life. 
Thus, BCD-085 can be recommended for further clinical development in the target 
population of patients. With the current knowledge from clinical studies of other drugs having 
similar mechanisms of action, psoriasis is believed to be highly sensitive to the IL-17 blockade. 
Investigating it in the population with moderate to severe plaque psoriasis will allow evaluating 
the therapeutic potential and characterize the safety of an innovative drug BCD-085. 
 


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1.4. Brief description of known and potential risks and benefit for study subjects (benefit/risk 
balance) 
1.4.1. Benefit assessment 
BCD-085 is an innovative drug the toxicity, safety, and pharmacokinetics of which was 
investigated in animals and in phase I clinical study in healthy volunteers. On the basis of the 
known biological effects of interleukin-17 and its role in the pathogenesis of autoimmune diseases, 
it is believed that the use of this drug in psoriasis patients will significantly reduce the 
inflammation and the severity of cutaneous and joint (if available) components, prevent 
stigmatization and early disability and improve the quality of life. The initiated clinical trial aims 
at defining the effective dose in a limited population, which means that some of the study subjects 
may not get any personal benefit from the study, except for a detailed medical examination. 
However, study results will be of high scientific value and, potentially, will help to introduce in 
clinical practice a highly effective medicine for the treatment of severe autoimmune diseases. 
1.4.2. Risk assessment 
BCD-085 is a new drug, so its effects in humans are not enough investigated. PD effects 
of blocking human IL-17 
 
 
 that BCD-085 may increase the risks of infections, 
including severe ones, and reactivation of latent opportunistic infections. However, BCD-085 in 
this study will be given to patients only after they undergo a complete screening examination 
(including that for chronic infections). Thus, it is expected that the risk of infectious complications 
for the patients involved in the study will be minimal. A risk of allergic reactions cannot be ruled 
out in subjects with hypersensitivity to ingredients of BCD-085. The method of administration 
(SC) and protein nature of BCD-085 suggest that there is a risk of injection site reactions. 
BCD-085 is a highly organized protein molecule with targeted immunotropic effects. Thus, 
it is necessary to identify potential risks of acute immune reactions after its first administration in 
humans. 


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Non-clinical studies 
reliably showed that BCD-085 does not have any cytotoxicity, does not lead to acute immune 
reactions at the injection site or adjacent areas, and does not have any cross-reactivity to human 
tissues. These results are also substantiated by the available data gained during the use of drugs 
with a similar mechanism of action (ixekizumab, secukinumab, brodalumab). BCD-085 does not 
have any pathogenetic mechanisms that can lead to acute immune reactions (which are not related 
to immediate-type hypersensitivity). Therefore, these reactions are unlikely to occur 
A completed phase I clinical study in healthy volunteers demonstrated that SC injections 
of BCD-085 at a wide range of doses (0.05 mg/kg to 3.0 mg/kg) rarely is associated with any 
adverse events, among which there were cases of elevated liver transaminases and one event of 
neutropenia. All AEs were mild (severity grade 1, CTCAE), short-term, and successfully resolved 
in all patients. It is assumed that the risk of such conditions or their more severe forms among the 
participants of this clinical study is minimal. 
1.4.3. Conclusions 
Findings from the physicochemical investigation, non-clinical development, and clinical 
studies of PK, safety, and tolerability in healthy volunteers provide the evidence of the favorable 
safety profile of BCD-085 and its potential efficacy in chronic inflammation. Thus, it is expected 
that the use of BCD-085 in the further clinical program, including in patients with psoriasis, will 
have a positive outcome with the low risk of adverse reactions. Thus, the overall risk/benefit 
balance with BCD-085 is considered favorable for the patients.  


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1.5. Description and justification of the route of administration, dosing regimen, and 
treatment course 
1.5.1 Description and justification of the study design 
This clinical trial was designed as a multicenter, double-blind, randomized study of the 
efficacy and safety to be run in 4 parallel arms, patients in 3 of which will receive different doses 
of BCD-085 (40 mg, 80 mg, and 120 mg), and patients in one arm will receive placebo. 
Since the planned population size is 120 patients with moderate to severe plaque-type 
psoriasis, it is unlikely that all of them can be recruited at one study site. To ensure the optimal 
timing, patients will be recruited at several sites.  
In this study, effects of BCD-085 will be compared with the effects of placebo to make 
adequate and objective conclusions on the efficacy and safety of the test product. The use of 
placebo is a standard approach in the clinical development of systemic medications for the 
treatment of psoriasis, which can be illustrated by clinical studies of ixekizumab, brodalumab, and 
secukinumab [15-21]. The necessity of using a placebo in the development of systemic 
medications is also mentioned in the EMA’s guidelines on clinical investigation of medicinal 
products for the treatment of psoriasis [CHMP/EWP/2454/02 corr, 2004]. 
The double-blind design is used to reduce the bias during the physician’s and patient’s 
assessment of treatment results, minimize systemic errors, and, therefore, to improve the validity 
of study results. 
The test drug and placebo will be given in parallel to patients in different arms. This is 
important to obtain objective results and eliminate the possibility of external factors to affect the 
treatment efficacy and safety. It is known, for example, that psoriasis patients commonly have 
seasonal exacerbations, and by using the parallel-group design, we eliminate the effect of the 
season on the study results. 
Randomization ensures that any factors that can affect treatment results are uniformly 
distributed by study groups, thus allowing investigators to attribute differences in responses 
directly to the investigational product used. 
One of the objectives of the phase II study is to find the effective dose and dosing regimen 
for the drug being investigated. At early development, the treatment duration should be enough to 
establish the efficacy and safety of the drug but should not be too long because not all doses used 
will produce the best possible benefit. The EMA guidelines [CHMP/EWP/2454/02 corr, 2004] 


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state that the primary efficacy data in the population of psoriasis patients can be obtained after the 
drug was used for 8 to 12 weeks [CHMP/EWP/2454/02 corr, 2004].  
The primary endpoint of this study is the proportion of patients with a PASI 75 response at 
Week 12. This is a sensitive indicator for patients with moderate to severe plaque psoriasis. It 
should be noted that a treatment duration of 12 weeks with an assessment of the proportion of 
PASI75 responders is widely used in clinical development to evaluate the efficacy of psoriasis 
drugs and is recommended in the EMA’s guidelines on clinical investigation of medicinal products 
indicated for the treatment of psoriasis [EMEA/CHMP/EWP/2454/02 corr, 2004]. This approach 
had been used in phase II clinical studies of ixekizumab, brodalumab, and secukinumab [15, 17, 
19, 20]. 
The use of the PASI alone may not be enough for the throughout efficacy assessment, so the 
clinical course of psoriasis in the study will be comprehensively assessed by using the changes in 
the body surface area (BSA) affected by psoriasis, static Physician’s Global Assessment (sPGA), 
nail psoriasis severity index (NAPSI), absolute PASI values, and other indicators. This is 
consistent with the recommendations stated in the EMA’s Guideline on Clinical Investigation of 
Medicinal Products Indicated for the Treatment of Psoriasis [EMEA/CHMP/EWP/2454/02corr, 
2004]. 
The recent findings suggest that interleukin-17 pays a key role in the development of 
psoriasis. Clinical studies of drugs blocking the IL-17 signaling (ixekizumab, brodalumab, and 
secukinumab) demonstrate high efficacy of this approach in the treatment of patients with 
moderate to severe plaque-type psoriasis with the PASI75 response seen in 70% to 80% of patients 
as early as at Week 12 of treatment. Thus, moderate to severe plaque-type psoriasis is considered 
a sensitive enough model for clinical investigation of BCD-085. 
1.5.2. Description and justification of the route of administration, dosing regimen, and 
treatment course 
Patients will be given BCD-085 at a dose of 40/80/120 mg or placebo as SC injections on 
Day 1/Week 0, Day 1/Week 1, Day 1/Week 2, Day 1/Week 4, Day 1/Week 6, Day 1/Week 8, and 
Day 1/Week 10. The patients will be followed up until Week 14 after the first dose. 
BCD-085 is a potential therapeutic candidate for the long-term management of psoriasis. To 
make the drug more convenient for the patients, it is planned to be used as SC injections. This 
route of administration has several advantages: patients can give injections to themselves, or 
injections can be made in the outpatient settings. Thus, it is reasonable to study the efficacy, safety, 


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pharmacokinetics, and immunogenicity of BCD-085 in patients with the same route of 
administration that is planned to be implemented in routine clinical practice. 
The doses of BCD-085 and the dosing frequency used in this study were chosen based on 
the available information on approved anti-IL-17 monoclonal antibodies and those under 
development. The most investigated drugs in this category are ixekizumab (Eli Lilly, USA), which 
is now in phase III trials, and secukinumab (Cosentyx®, Novartis, Switzerland), which is the only 
anti-IL-17 monoclonal antibody approved for human use. 
 
In phase I study of BCD-085, all tested doses (including those exceeding the expected therapeutic 
dose) demonstrated the favorable safety profile. Therefore, no increased risk is expected for 
patients who will be given BCD-085 at doses different from the planned effective dose. 
The main PK parameters of ere characterized in a phase I trial. This trial involved several 
cohorts of healthy volunteers who were given SC injections of BCD-085 at doses calculated per 1 
kg of the body weight and individual for each cohort (details are presented in section 1.3.2).  
Clinical trials  
It has been shown that doses closest to those planned to be used in phase II trial were given 
to patients from cohorts 4-6 (with an account for patients body weight). Thus, it is considered that 
BCD-085 at doses of 40 mg, 80 mg, and 120 mg will have pharmacokinetics similar to that seen 
 
15 
Cosentyx® 
Assessment 
report, 
EMA/CHMP/389874/2014, 
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR-
Public_assessment_report/human/003729/WC500183131.pdf 
16Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, Cameron GS, Erickson J, Zhang L, 
Secrest RJ, Ball S, Braun DK, Osuntokun OO, Heffernan MP, Nickoloff BJ, Papp K; UNCOVER-2 and UNCOVER-
3 investigators.Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 
and UNCOVER-3): results from two phase 3 randomized trials.Lancet. 2015 Aug 8;386(9993):541-51. 
 


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in cohorts 4-6 with the half-life of 16 to 18 days. Based on this, BCD-085 injections should be 
given with an interval of about 2 weeks.  
At baseline, patients have an acute inflammation that has to be resolved as soon as possible. 
This requires using induction (higher) doses or an induction phase (more frequent injections). 
Clinical trials of drugs inhibiting the signaling of interleukin-17 utilize both the first [16] and the 
second [17, 18, 20, 21] approaches. In this study, patients will receive BCD-085 once weekly 
during the induction phase. Then they will be transferred to the maintenance phase and receive the 
drug once every 2 weeks. 
Thus, the doses (40 mg, 80 mg, and 120 mg), regimen, and route of administration to be 
used in this study were chosen on the basis of the findings from non-clinical and phase I clinical 
studies of BCD-085 and available information on other anti-IL-17 monoclonal antibodies, taking 
convenience to patients into account. 
 
1.5.3. Justification of placebo use 
About every 4th patient in this study will receive placebo. This is necessary to draw unbiased 
conclusions on the efficacy and safety of the study drug and is a standard approach for 
investigating systemic medications for psoriasis. The necessity of using a placebo in the 
development of systemic medications is also mentioned in the EMA’s guidelines on clinical 
investigation of medicinal products for the treatment of psoriasis [CHMP/EWP/2454/02 corr, 
2004]. 
Patients involved in this study will net be exposed to excessive risk because of getting a 
placebo. All patients are allowed to continue systemic non-biologic medications and, in some 
cases, glucocorticoids. Topical glucocorticoids will be permitted to be used on the face, armpits, 
and genitals. If the disease worsens and requires additional therapy, patients can always 
discontinue the study and receive all the medications he/she needs. It should also be noted that the 
therapeutic effect of BCD-085 in psoriasis patients has not yet been investigated, so we cannot 
clearly state the benefit of being in the active-treatment arm.  
This being said, the use of placebo in one of the arms does not pose any threat to the patients' 
safety and is in full compliance with the international guidelines and practice of studies of 
medicinal products for the treatment of psoriasis. 
 


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1.6. Clinical study compliance with the regulatory requirements 
This clinical study will be conducted in accordance with the Protocol. The clinical study was 
developed in compliance with the GCP principles, current law and regulatory requirements of the 
participating countries. 
1.7. Description of study population 
Males and females aged from 18 to 65 years, who had with stable moderate to severe plaque 
psoriasis and who did not respond to or were candidates for systemic therapy including TNF-α 
inhibitors or UV therapy. 
1.8. References 
1. Weger W. Current status and new developments in the treatment of psoriasis and psoriatic 
arthritis with biological agents // Br J Pharmacol. 2010 May-Jun; 160(4): 810-820.  
2. Nestle FO, Kaplan DH, Barker J. N Engl J Med 2009;361:496-509 
3. Albanesi C, De Pità O, Girolomoni G. Resident skin cells in psoriasis: a special look at the 
pathogenetic functions of keratinocytes. J Clin Oncol 2007; 25: 581-8. 
4. Monteleone G, Pallone F, MacDonald TT et al. Psoriasis: from pathogenesis to novel 
therapeutic approaches. Clin Sci (Lond) 2011; 120:1–11. 
5. Lowes MA, Kikuchi T, Fuentes-Duculan J et al. Psoriasis vulgaris lesions contain discrete 
populations of Th1 and Th17 T cells. J Clin Oncol 2008; 128: 1207-11. 
6. Ortega C, Fernández AS, Carrillo JM et al. IL-17-producing CD8+ T lymphocytes from 
psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J 
Clin Oncol 2009; 86: 435-43. 
7. Eyerich S, Eyerich K, Pennino D et al. Th22 cells represent a distinct human T cell subset 
involved in epidermal immunity and remodeling. J Clin Oncol 2009; 119: 3573-85. 
8. Krueger JG. The immunologic basis for the treatment of psoriasis with new biologic 
agents. J Am Acad Dermatol 2002;46:1-23. 
9. Nickoloff BJ, Xin H, Nestle FO, Qin JZ. The cytokine and chemokine network in psoriasis. 
J Clin Pharmacol 2007;25:568—-73. 
10. Chiricozzi A, Krueger JG. IL-17 targeted therapies for psoriasis. Expert Opin Investig 
Drugs. 2013 Aug;22(8):993-1005.  


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11. Zaba LC, Suarez-Farinas M, Fuentes-Duculan J, et al. Effective treatment of psoriasis with 
etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. 
J Allergy Clin Immunol 2009;124(5):1022-10. 
12. Johnson-Huang LM, Suarez-Farinas M, Sullivan-Whalen M, et al. Effective narrow-band 
UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. 
Br J Dermatol 2010;130(11):2654-63. 
13. Zaba LC, Cardinale I, Gilleaudeau P, et al. Amelioration of epidermal hyperplasia by TNF 
inhibition is associated with reduced Th17 responses. J Maternal-Fetal Med 2007; 
204:3183-94. 
14. Haider AS, Lowes MA, Suarez-Farinas M, et al. Identification of cellular pathways of 
“Type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic 
cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in 
psoriasis. J Rheumatol 2008;180:1913-20. 
15. Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, 
Banerjee S. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque 
psoriasis. N Engl J Med. 2012 Mar 29;366(13):1190-9. 
16. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, Cameron GS, 
Erickson J, Zhang L, Secrest RJ, Ball S, Braun DK, Osuntokun OO, Heffernan MP, 
Nickoloff BJ, Papp K; UNCOVER-2 and UNCOVER-3 investigators. Comparison of 
ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and 
UNCOVER-3): results from two phase 3 randomised trials // Lancet. 2015 Aug 
8;386(9993):541-51.  
17. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17-receptor 
antibody for psoriasis. N Engl J Med 2012;13:1181-9 
18. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, Spelman L, 
Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB, Bachelez H, Wu JJ, Crowley J, 
Langley RG, Blicharski T, Paul C, Lacour JP, Tyring S, Kircik L, Chimenti S, Callis Duffin 
K, Bagel J, Koo J, Aras G, Li J, Song W, Milmont CE, Shi Y, Erondu N, Klekotka P, 
Kotzin B, Nirula A. Phase 3 Studies Comparing Brodalumab with Ustekinumab in 
Psoriasis. N Engl J Med. 2015 Oct;373(14):1318-28. 
19. Papp KA, Langley RG, Sigurgeirsson B, et al. Efficacy and safety of secukinumab in the 
treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-
controlled phase II dose-ranging study. Br J Dermatol 2013;168(2):412-21. 


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20. Rich P, Sigurgeirsson B, Thaci DP, et al. Secukinumab induction and maintenance therapy 
in moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo-controlled 
phase II dose-ranging study. Br J Dermatol 2012; [Epub ahead of print]. 
21. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa 
H, Spelman L, Sigurgeirsson B, Rivas E, Tsai TF, Wasel N, Tyring S, Salko T, Hampele 
I, Notter M, Karpov A, Helou S, Papavassilis C; ERASURE Study Group; FIXTURE 
Study Group. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 
2014 Jul;371(4):326-38. 
22. Kavanaugh A. Ethical and practical issues in conducting clinical trials in psoriasis and 
psoriatic arthritis.Ann Rheum Dis 2005;64:ii46-ii48. 
23. Ariza ME, Williams MV, Wong HK. Targeting IL-17 in psoriasis: from cutaneous 
immunobiology to clinical application. Clin Immunol. 2013 Feb;146(2):131-9. 
24. Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J 
Dermatol. 2012 Oct;167(4):717-24. 
25. Harper EG, Guo C, Rizzo H, et al. Th17 cytokines stimulate CCL20 expression in 
keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest 
Dermatol. 2009 Sep;129(9):2175-83. 
26. Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J 
Dermatol. 2012 Oct;167(4):717-24. 
27. Fossiez F, Djossou O, Chomarat P, et al. T cell interleukin-17 induces stromal cells to 
produce proinflammatory and hematopoietic cytokines. J Exp Med. 1996 Jun 
1;183(6):2593-603. 
28. Miossec P, Korn T, Kuchroo VK. (2009) Interleukin-17 and type 17 helper T cells. N Engl 
J Med. 2009 Aug 27;361(9):888-98. 
29. Federal Law 61-FZ of April 12, 2010: On the Circulation of Medicines. 
30. National standard of the Russian Federation GOST R 52379-2005: Good Clinical Practice 
(approved by Decree No 232-st of September 27, 2005 of the Federal Agency for Technical 
Regulation and Metrology). 
31. Decree No 266 "Concerning the approval of Good Clinical Practice in the Russian 
Federation”, 19.06.2003. 
 
 


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2. STUDY PURPOSE AND OBJECTIVES 
2.1 Study aims 
Study purpose: To find an effective and safe dose of BCD-085 for multiple injections in patients 
with moderate to severe plaque-type psoriasis. 
2.2 Study objectives 
1. To determine the number of patients in each study arm who achieved a PASI 75 at Week 
12 of treatment 
2. To determine the number of patients in each study arm who achieved a PASI 75 at weeks 4 
and 8 of treatment 
3. To determine the number of patients in each study arm who achieve a PASI 50/90 at weeks 
4, 8, and 12 of treatment  
4. To evaluate the PASI improvement from baseline in each study arm at weeks 4, 8, and 12.  
5. To evaluate the improvement from baseline in the body surface area (BSA) affected by 
psoriasis in each study arm at weeks 4, 8, and 12 
6. To evaluate the improvement from baseline in the nail psoriasis severity index (NAPSI) in 
each study arm at weeks 4, 8, and 12 
7. To determine the mean improvement from baseline in the intensity of pruritus measured by 
VAS (0-100 mm) in each study arm at weeks 1, 4, 8, and 12 
8. To evaluate the proportion of patients in each study arm who achieve an sPGA score 0 or 1 
at weeks 4, 8, and 12 relative to baseline 
9. To investigate patients’ quality of life in each study arm at weeks 4, 8, and 12 according to 
SF-36 and DLQI. 
10. To evaluate the proportion of patients in each study arm who develop adverse events with 
repeated administration of 40 mg, 80 mg, and 120 mg BCD-085 as compared to placebo 
 
 
 
 
 
 


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3.0 HYPOTHESIS 
This clinical study is based on the hypothesis that the clinical efficacy of BCD-085 defined 
based on the proportion of patients with moderate to severe plaque psoriasis who achieved a 
PASI75 at Week 12 of treatment is higher than the same effect seen with placebo. 
4. STUDY DESIGN 
4.1. Primary and secondary endpoints 
4.1.1 Primary endpoint 
• The proportion of patients in each study arm who achieved a PASI 75 at Week 12 
of treatment 
4.1.2 Secondary endpoints 
Efficacy endpoints: 
• The proportion of patients in each study arm who achieved a PASI 75 at weeks 4 
and 8 of treatment 
• The proportion of patients in each study arm who achieved a PASI 50/90 at weeks 
4, 8, and 12 of treatment  
• The relative PASI improvement from baseline in each study arm at weeks 4, 8, 
and 12  
• The relative BSA improvement from baseline in each study arm at weeks 4, 8, and 
12 
• The relative NAPSI improvement from baseline in each study arm at weeks 4, 8, 
and 12 
• The mean change from baseline in the intensity of pruritus measured by VAS (0-
100 mm) in each study arm at weeks 1, 4, 8, and 12 
• The proportion of patients in each study arm who achieved an sPGA score 0 or 1 
at weeks 4, 8, and 12 relative to baseline 
 
17 If neutralizing antibodies are detected in the serum samples collected for PK study. 


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• The mean change from baseline in the QoL score in each study arm (assessed 
using the DLQI and SF-36 scales) at weeks 4, 8, and 12. 
Safety endpoints: 
• The proportion of patients who developed SAEs 
• The proportion of patients who developed AEs  
• The proportion of patients who developed administration site reactions 
• The proportion of patients who developed grade 3/4 AEs/SAEs 
• The proportion of patients who discontinued the study due to AEs/SAEs. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2. Description of the study type/design, study flow-chart, study procedures and periods 
Study design 
This international multicenter study uses a double-blind comparative design. The purpose 
of the study is to determine a therapeutically effective dose of BCD-085 to be repeatedly 
administered in patients with moderate to severe plaque-type psoriasis, as compared with placebo. 


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The study is planned to include 120 adults who had moderate to severe plaque psoriasis 
stable for at least 6 months before inclusion in the study (i.e. there were no changes in 
morphological appearance, no severe aggravation or worsening of the disease occurred during this 
time, as judged by the investigator), 10% or greater body-surface area involvement, a psoriasis 
area and severity index (PASI) of 12 or more, and a sPGA score of 3 or more. 
Before being included in the study, patients must read and sign the informed consent form 
and undergo a  screening examination (not longer than 4 calendar weeks) to confirm that they are 
eligible for the study. The Protocol does not stipulate any additional requirements for the diet or 
physical activity during the screening or study period. 
 
Stratification and randomization 
When all screening procedures are completed and the investigator approves patient’s 
inclusion in the study, patients are stratified by body weight (≤ 80 kg / ≥81 kg), prior use of 
monoclonal antibodies for psoriasis (MAb-treated / MAb-naive), current use of systemic non-
biologics (yes/no), PASI score (< 20 / ≥ 20), signs of psoriatic arthritis  (absent / present). After 
stratification, the patients are randomized 1:1:1:1 to one of four study arms: 
• Arm 1: patients will receive subcutaneous injections of 40 mg BCD-085 (1.0 mL) once a 
week for the first 3 weeks (induction period) and then once every 2 weeks (maintenance 
period). For blinding purposes, these patients will be given two SC injections of placebo 
(1.0 mL each) together with each injection of BCD-085. Thus, the drug will be 
administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction period), 
Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10 (maintenance 
period).  
• Arm 2: patients will receive 80 mg BCD-085 (two SC injections 1.0 mL each) once a 
week for the first 3 weeks (induction period) and then once every 2 weeks (maintenance 
period). For blinding purposes, these patients will be given one SC injection of placebo 
(1.0 mL) together with the injections of BCD-085. Thus, the drug will be administered on 
Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction period), Day 1 of Week 
4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10 (maintenance period). 
• Arm 3: patients will receive 120 mg BCD-085 (three SC injections 1.0 mL each) once a 
week for the first 3 weeks (induction period) and then once every 3 weeks (maintenance 


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period). Thus, the drug will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 
1 of Week 2 (induction period), Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, 
and Day 1 of Week 10 (maintenance period). 
• Arm 4: patients will receive placebo as three 1.0 mL SC injections on Day 1/Week 0, Day 
1/Week 1, Day 1/Week 2, Day 1/Week 4, Day 1/Week 6, Day 1/Week 8, and Day 1/Week 
10. 
 
Because patients included in the PK analysis will be requested to provide multiple blood 
specimens during the first 24 h after the first injection, these patients may stay at the study site at 
the discretion of the investigator. 
 
Study periods 
• Screening (not more than 4 calendar weeks) 
• Therapy period: induction period and maintenance period: from Week 0 to Week 10 
• Follow-up: 4 calendar weeks (through Week 14) 
Nine visits to study sites are planned during 14 weeks of the active study period. During these 
visits, blood samples will be drawn for the efficacy, safety, 
 




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Treatment by study arms 
In this study, BCD-085 will be administered to patients in three of four study arms. 
Patients will receive 40 mg, 80 mg, or 120 mg BCD-085 as SC injections once weekly for the first 
three weeks (induction regimen) and then once every two weeks (maintenance regimen). Thus, the 
drug will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction 
period), Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10 (maintenance 
period). 
For blinding purposes, patients from 40 mg and 80 mg arms will receive two or one SC 
injection of placebo (1 mL each), respectively. 
Patients in the control arm will receive 3 SC injections of placebo (each injection is 
1.0 mL). Placebo to be used has the similar composition for all three arms and contains the same 
excipients that the BCD-085 dosage form. 
Regardless of the arm to which the patient is assigned, injections will be performed by an 
authorized site medical nurse directly in the study site. Injections can be given to the abdomen, 
hips, or upper arms. Injections should be given at least 5 cm apart. 
During the entire study period, patients are not allowed to use phototherapy (UV-B), 
photochemotherapy (PUVA), biologics other than BCD-085, and live or attenuated vaccines. 
The patients are allowed to use systemic non-biologic therapies (methotrexate, 
sulfasalazine, chlorambucil, leflunomide, cyclosporine A, azathioprine, aromatic retinoids 
(acetretin), and glucocorticoids (> 10 mg of prednisolone equivalent per day) if their dose was 
stable for 4 weeks before signing the informed consent and through the entire screening period). 
Patients are not allowed to change their systemic non-biologic treatment during the study, increase 
the dose, or add any new medications of this category. Patients are allowed to discontinue systemic 
non-biologic therapies only if he/she has any life- or health-threatening adverse effects due to this 
treatment. Any modifications of the dosing regimen or dose reduction for systemic non-biologic 
therapy can be made only after reconciliation with the Sponsor. 
The patients may use topical glucocorticoids on the face, underarm, and genitals. The 
patients may use topical moisturizing products, emollients, oils or salicylic acid-based products if 
necessary. The patients should discontinue all local skin products (medications or cosmetics) 24 
hours before the planned PASI assessment. 
Management of patients after the end of the study 
Management and follow-up of patients who completed/discontinued the study due to any 
reason are to be defined by the attending physician. 


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Study procedures 
To establish whether patients meet the inclusion/exclusion criteria and to assess the 
treatment efficacy (for enrolled subjects), patients will undergo, within the timeframes specified 
by the Protocol, a comprehensive medical exam including: 
• Taking baseline clinical characteristics and medical history 
• Physical examination 
• Measuring blood pressure and wrist pulse 
• Electrocardiography 
• Chest X-ray / fluorography (front view) 
• Blood hematology  
• Blood biochemistry 
• Pregnancy test18 
• Assessment of the patient’s infection status (Diaskintest® or blood testing for interferon 
gamma (QuantiFERON test)); if these tests are impossible to perform, the Mantoux test 
can be done and the patient can be examined by the TB specialist (required if the 
Diaskintest® or QuantiFERON test results are uncertain or if the Mantoux results are 
uncertain or positive), anti-HIV antibodies [HIVAg/Ab Combo], HBs-antigen, anti-HBcor 
antibodies [IgG + IgM/ IgG/ IgM], and anti-HCV antibodies [IgG + IgM], qualitative PCR 
for HCV RNA / HBV DNA (only if the patient was positive for respective antibodies), 
consultation with an infectious disease specialist (required only if the patient is positive for 
anti-HBcor antibodies or anti-HCV antibodies), microprecioitation reaction, and a direct 
hemagglutination assay (T. pallidum) 
• Calculation of the body surface area affected by psoriasis (BSA) 
• Assessment of the area and severity of psoriasis with the PASI score 
• Assessment of psoriasis severity with sPGA19 
• The severity of pruritus assessed with the visual analog scale (0-100 mm) 
• Assessment of psoriasis involvement of nails (NAPSI) 
• DLQI and SF-36 questionnaires. 
To measure the efficacy of treatment in the timeframes specified by the Protocol, the changes over 
time in the PASI, NAPSI, and sPGA scores, VAS scores for pruritus intensity, and the quality of 
 
18 Pregnancy test is required only for women of childbearing potential and does not apply to post-menopausal 
women. 
19Static Physicians Global Assessment. 


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life (DLQI and SF-36 scores) will be evaluated. 
 
 
For safety evaluation, the following will be closely monitored: all general disorders 
(including fever and flu-like symptoms), abnormal physical signs (BP, wrist pulse), infections, 
abnormalities in certain laboratory values (CBC results: hemoglobin, RBC, platelets, WBC 
including changes in the WBC differential, ESR; blood biochemistry: glucose, total  bilirubin, 
indirect bilirubin, ALT, AST, GGT, LDH, total protein, creatinine, urinalysis; coagulation profile: 
prothrombin ratio, APTT), cardiac disorders (ECG), lung abnormalities (chest X-ray / 
fluorography). 
 
 
 
 
 
 
4.3. Measures to minimize/eliminate bias 
4.3.1. Distribution of patients by study sites 
Patients' recruitment at study centers will be performed on a competitive basis. After the 
inclusion of the 120th patient, recruitment to the study will be stopped. Recruitment can be re-
opened if the Sponsor’s audit reveals patients who do not meet the eligibility criteria or patients 
who majorly violate the Protocol (with no explanation timely provided to the Sponsor). 
4.3.2. Procedure of assigning study IDs 
Patients will be randomized, stratified, and assigned study numbers according to internal 
guidelines of JSC BIOCAD. 
Each study site will be assigned a 2-digit ID number. For example, the first site will be 
numbered 01, the second – 02, the third – 03, etc. 
After signing an informed consent form, each patient will receive a 5-digit screening 
number consisting of a 2-digit center number and a 3-digit patient’s number (continuing 
numbering in sequence, as patients are enrolled in this center). This should be recorded in source 
documents and a patients’ screening log. For example, in the study center 02, the first patient who 


















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4.3.5. Blinding and subject-specific lots of investigational products 
Neither investigators, not patients will be aware of whether the active treatment or placebo 
is used in each particular patient. The investigator (the principal investigator, a co-investigator 
responsible for the therapy of this patient) receives BCD-085/placebo in identical secondary 
packaging (cartons). The drugs differ only by their lot numbers. The lot number is individual for 
the subject. During therapy, the subject may receive the investigational product of several batches 
but they will be assigned the same lot number.  
Individual kits for the patients in each arm will be prepared to be used at scheduled 
timepoints (Week 0, Week 1, Week 2, Week 4, Week 6, Week 8, and Week 10). Each kit contains 
3 visually indistinguishable pre-filled syringes according to the arm to which the patient is 
assigned: 
Each kit includes extra packs of the patient-specific lots to be used if any of the pre-filled syringes 
specified for a certain visit are damaged or lost. 
 
4.4. Study therapy, doses, and dosage regimens of investigational products. Pharmaceutical 
form, packaging, and labeling of investigational products 
4.4.1. Study therapy, doses, and dosage regimens of investigational products 
In this study, BCD-085 will be administered to patients in three of four study arms. 
Patients will receive 40 mg, 80 mg, or 120 mg BCD-085 as SC injections once weekly for the first 
three weeks (induction regimen) and then once every two weeks (maintenance regimen). Thus, the 
drug will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction 


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period), Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10 (maintenance 
period). 
For blinding purposes, patients from 40 mg and 80 mg arms will be given two or one SC 
injection of placebo (1 mL each), respectively. 
Patients in the control arm will receive three SC injections of placebo. Placebo to be used 
has the similar composition for all three arms and contains the same excipients that the BCD-085 
dosage form. 
Regardless of the arm to which the patient is assigned, injections will be performed by an 
authorized site medical nurse directly in the study site. Injections can be given to the abdomen, 
hips, or upper arms. Injections should be given at least 5 cm apart. The overall duration of all three 
injections should not exceed 15 min from the beginning of the first injection. 
4.4.2. Pharmaceutical form, packaging, and labeling of investigational products 
The test drug and placebo will have similar packaging differing only by the lot number and 
shelf life.  
4.4.2.1. Test drug 


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4.4.2.2. Placebo 
4.4.2.3. Labeling of investigational products 
This study is blind so the investigational products will be labeled the same way. 
According to Article 46 of Federal Law 61-FZ “On the Circulation of Medicines” of April 
12, 2010 and regulatory requirements of the participating countries, 
 
 
 


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Both primary and secondary package will also have the following labeling: “For Clinical 
Trials Only”. 
The secondary package will also contain the following information: protocol ID, study site 
number, patient’s ID (entered by the investigator). 
4.5. Expected duration of the study and subjects’ participation in the study 
The expected duration of the study is 26 months, which includes patients' recruitment (up 
to 12 months), treatment period, follow-up period, and data collection and statistical processing. 
It is planned that each subject will participate in the study for up to 18 weeks, including screening 
(up to 4 weeks), active study phase (10 weeks), and follow-up (4 weeks). 
4.6. Study periods 
4.6.1 Study schedule (visits and procedures) 
The study includes the following periods: 
- Screening (Days -28 to 0) 
- Treatment period (weeks 1 to 10) 
- Follow-up (weeks 11 to 14) 
Table 14 lists all the procedures to be performed in the study. All the data obtained during 
these assessments 
 must be confirmed by the source documents.  
Screening/baseline assessment should be performed within 28 days before the estimated 
date of the first infusion of BCD-085/placebo Prior results may be used for certain screening tests 
and exams (see section 4.7 for details). At the end of the screening period, the patient should be 
assessed for the inclusion/exclusion criteria and undergo randomization. 








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4.6.2. Procedures by visits 
Procedures of the screening period 
The screening period starts when the patient signs the informed consent form and lasts for 
not more than 4 weeks (Days -28 to 0) until the day when the patient is included in the study. 
• Check informed consent is taken from the patient 
• Take medical history and document any patient complaints 
• Collect the information about concomitant treatments (and treatments used within 
1 month before inclusion in the study) 
• BP, wrist pulse, and body temperature 
• Physical exam (including body weight and height measurements) 
• Complete blood count34 (3 mL) 
• 
Bloodbiochemistry34 (9 mL) 
• Coagulation profile (6 mL) 
• Tests for HIV, HCV, HBV, and syphilis (12 mL) 
• Urinalysis 
• ECG 
• Chest x-ray / fluorography 
• Pregnancy test35 
• Assessment of the area and severity of psoriasis with PASI 
• Assessment of psoriasis severity with sPGA 
• Assessment of the body surface area affected by psoriasis (BSA) 
• Assessment of psoriasis involvement of nails (NAPSI) 
• 
 
• The patient fills out the VAS for pruritus 
• DLQI and SF-36 questionnaires 
 
34 At screening, the test can be repeated once, if the first result did not meet the eligibility criteria. 
35 Pregnancy test is required only for women of childbearing potential and does not apply to post-menopausal 
women. 


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• TB test36 (cutaneous Diaskintest® or drawing blood for QuantiFERON test37 
(testing blood plasma for the presence of gamma interferon)) 
• Checking for eligibility (inclusion/non-inclusion criteria) 
• Inclusion in the study (randomization and stratification) 
• Documenting SAEs 
Total blood volume taken at the visit: 30 mL 
Procedures of Visit 1 (Day 1, Week 0): 
• 
Physical exam (including body weight) 
• The patient fills out the VAS for pruritus 
 
 
 
 
 
• Collecting the information about concurrent therapy 
• 
 
 
 
• Administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• BP, pulse, and tº (measured any time before and immediately after the injection of 
BCD-085) 
• 
 
 
 
 
• Assessment of the injection site reaction (twice: 4 h and 8 h after the injection of 
BCD-085/placebo) 
• Documenting AEs/SAEs 
 
36If Diaskintest®/QuantiFERON test cannot be performed, the Mantoux test can be done instead. The patients 
with uncertain or positive Mantoux test results are allowed in the study if the following conditions are met: a qualified 
specialist excluded TB infection (a written report had to be provided) and the chest X-ray exam performed within 1 
month before randomization revealed no signs of active TB infection. 
37QuantiFERON test is recommended if skin tests cannot be performed (skin lesions in the middle of the 
inside forearm). 
 
 


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Total blood volume taken at the visit: 13 mL (for all patients) 
 
. 
Procedures of Visit 2 (Day 2 of Week 0). 
 
 
• 
 
• Collection of the information about concurrent therapy 
• Documenting AEs/SAEs 
 
Procedures of Visit 3 (Day 3 of Week 0). 
 
 
• 
 
• Collection of the information about concurrent therapy 
• Documenting AEs/SAEs 
 
Procedures of Visit 4 (Day 4 of Week 0). 
 
 
• 
 
• Collection of the information about concurrent therapy 
• Documenting AEs/SAEs 
 
 
Procedures of Visit 5 (Day 7 of Week 0). 
 
 
• 
 
• Collection of the information about concurrent therapy 
• Documenting AEs/SAEs 
 


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Procedures of Visit 6 (Day 1, Week 1) performed 7 days after the first dose of BCD-
085/placebo: 
• Physical exam (including body weight) 
• 
 
 
 
 
 
 
• Complete blood count (3 mL) 
• Blood biochemistry (9 mL) 
• Coagulation profile (6 mL) 
• Urinalysis 
• The patient fills out the VAS for pruritus 
• 2nd administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• Blood pressure, heart rate and body temperature (immediately after dosing) 
• ECG 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
Total blood volume taken at the visit: 
 18 mL for all 
other patients. 
 
Procedures of Visit 7 (Day 1, Week 2) performed 7 days after the 2nd dose of BCD-
085/placebo: 
• Physical exam (including body weight) 
• 
 
 
 
 
• 3rd administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
 
 
 
 
 


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• Blood pressure, heart rate and body temperature (immediately after dosing) 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
 
 
Procedures of Visit 8 (Day 1, Week 4) performed 14 days after the 3rd dose of BCD-
085/placebo: 
• Physical exam (including body weight) 
• Assessment of the area and severity of psoriasis with PASI 
• Assessment of psoriasis severity with sPGA 
• Assessment of the body surface area affected by psoriasis (BSA) 
• 
 
• The patient fills out the VAS for pruritus 
• DLQI and SF-36 questionnaires 
• 
 
 
 
 
• 4th administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• Blood pressure, heart rate and body temperature (immediately after dosing) 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
 
 
Visit 9 (Day 1, Week 6) performed 14 days after the 4th dose of BCD-085/placebo: 
• Physical exam (including body weight and height measurements) 
• 
 
 
 
 
 
 
 
 
 


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• 5th administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• Blood pressure, heart rate and body temperature (immediately after dosing) 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
 
 
 
Visit 10 (Day 1, Week 8) performed 14 days after the 5th dose of BCD-085/placebo: 
• Physical exam (including body weight) 
• Assessment of the area and severity of psoriasis with PASI 
• Assessment of psoriasis severity with sPGA 
• Assessment of the body surface area affected by psoriasis (BSA) 
• 
 
• The patient fills out the VAS for pruritus 
• DLQI and SF-36 questionnaires 
• Complete blood count (3 mL) 
• Blood biochemistry (9 mL) 
• Coagulation profile (6 mL) 
• Blood sampling for immunogenicity assay (8 mL) 
• 
 
 
 
 
• 6th administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• Blood pressure, heart rate and body temperature (immediately after dosing) 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
 
 
 


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Total blood volume taken at the visit: 
 26 mL 
. 
 
Visit 11 (Day 1, Week 10) performed 14 days after the 6th dose of BCD-085/placebo: 
• Physical exam (including body weight) 
• 
 
 
 
 
• 7th administration of BCD-085/placebo 
• Assessment of the injection site pain with VAS (immediately after the injection of 
BCD-085/placebo) 
• Blood pressure, heart rate and body temperature (immediately after dosing) 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
 
 
Visit 12 (Day 1, Week 12) performed 14 days after the 7th dose of BCD-085/placebo: 
• Physical exam (including body weight) 
• Assessment of the area and severity of psoriasis with PASI 
• Assessment of psoriasis severity with sPGA 
• Assessment of the body surface area affected by psoriasis (BSA) 
• Assessment of psoriasis involvement of nails (NAPSI) 
• 
 
• The patient fills out the VAS for pruritus 
• 
 
 
 
• Blood pressure, wrist pulse, and body temperature 
• Complete blood count (3 mL) 
• Blood biochemistry (9 mL) 
• 
 
• Coagulation profile (6 mL) 
• Urinalysis 
 
 
 


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• DLQI and SF-36 questionnaires 
• Collection of the information about concurrent therapy 
• Assessment of injection site reactions 
• Documenting AEs/SAEs 
Total blood volume taken at the visit: 
 23 mL 
. 
 
Visit 13 (any day of Week 14), performed 28-34 days after the 7th dose of BCD-085/placebo: 
• Physical exam (including body weight) 
• 
 
• Complete blood count (3 mL) 
• Blood biochemistry (9 mL) 
• Coagulation profile (6 mL) 
• 
 
• Chest x-ray / fluorography 
• Urinalysis 
• ECG 
• Blood pressure, wrist pulse, and body temperature 
• Collection of the information about concurrent therapy 
• Documenting AEs/SAEs 
• Completion of the study by the patient 
Total blood volume taken at the visit: 26 mL (for all patients) 
 
 
 
During unscheduled visits, the investigator must document AEs/SAEs. Other procedures are on 
the discretion of the investigator and must be entered in the CRF as comments to an unscheduled 
visit. 
4.7. Description of individual study procedures 
All scheduled clinical and laboratory procedures and timings are listed in Table 15. 
 
 
 














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− Ethnic origin 
− Reproductive potential [use of contraception (specify which measures), menopause state, its 
duration, sterilization, if applicable] 
− Medical history (infections in the past, chronic infectious-inflammatory diseases, a history of 
tuberculosis, contacts with a patient with tuberculosis, other chronic skin inflammatory 
disorders, immunodeficiency, concomitant conditions) with the onset/resolution dates (if 
applicable) 
− Medical history (approximate date of psoriasis onset, area and severity of psoriasis before and 
at screening, effects of treatment) 
− Medication history: 
A) Specify all medications that the patient has received for the treatment of psoriasis, with doses, 
dosing regimens, therapy duration, and efficacy of each medication, in the opinion of the 
Investigator. If the medication was discontinued, specify the reason. 
B) Specify any medications that the patient has been taking within 30 days before screening. 
Specify dose, dosage regimen, treatment duration, and the reason for discontinuation (if 
applicable). Medications for the treatment of psoriasis that the patient uses now of has been 
using within 30 days before screening must be recorded in the “Medication Therapy for 
psoriasis” section. 
 
4.7.2. Physical examination 
The following organs and systems must be assessed during the physical exam:  
− Height (at screening only) 
− Body weight (at screening and before each injection of BCD-085/placebo) 
− Skin and mucosa (visual examination, describe all pathological changes that are not due to 
psoriasis) 
− Lymphatic nodes (visual examination, palpation) 
− Ear/nose/throat, respiratory organs (examination, lung auscultation) 
− Cardiovascular system (heart auscultation, examination of major vessels area) 
− GI (examination, palpation of abdominal area) 
− Spleen size (palpation, percussion) 
− Spleen size (palpation, percussion) 
− Urogenital system (kidney punch, palpation of kidney and bladder area) 


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− Nervous system (meningeal signs, focal neurological signs) 
− Mental health (signs of depressive disorder, suicidal ideation, acute psychotic disorder) 
Examination must be performed at screening, Visit 1 (Day 1 of Week 0), Visit 6 (Day 1 of 
Week 1), Visit 7 (Day 1 of Week 2), Visit 8 (Day 1 of Week 4), Visit 9 (Day 1 of Week 6), Visit 
10 (Day 1 of Week 8), Visit 11 (Day 1 of Week 10), Visit 12 (Day 1 of Week 12), and Visit 13 
(any day of Week 14). 
4.7.3. Vital signs 
Vital signs include axillary body temperature (ºC), blood pressure (on one arm, mm Hg), 
and wrist pulse. 
Vital signs must be checked at screening, Visit 1 (Day 1 of Week 0, twice - any time before 
and immediately after the injection), Visit 6 (Day 1 of Week 1), Visit 7 (Day 1 of Week 2), Visit 
8 (Day 1 of Week 4), Visit 9 (Day 1 of Week 6), Visit 10 (Day 1 of Week 8), Visit 11 (Day 1 of 
Week 10), Visit 12 (Day 1 of Week 12), and Visit 13 (any day of Week 14). 
 
4.7.4. Laboratory tests 
Laboratory tests include CBC, blood biochemistry, coagulation pattern, 
 
, and urinalysis. In addition, markers of HIV, hepatitis B and 
C, and syphilis will be determined at screening. 
4.7.4.1. CBC 
CBC is performed at fasting in accordance with the standard procedure (fasting means at 
least 8 hours without food). This study includes the following CBC parameters: 
− Hemoglobin (g/L) 
− RBC (×1012/L) 
− WBC (×109/L) 
− Platelets (×109/L) 
− Neutrophils (×109/L) 
− Lymphocytes (×109/L) 
− Monocytes (×109/L) 
− ESR (mm/h) must be measured by Westergren method only. Any other method for 
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The volume of blood taken: 3 mL. 
Blood sampling is performed using standard procedures. 
CBC is done at screening, Visit 6 (Day 1 of Week 1), Visit 10 (Day 1 of Week 8), Visit 12 
(Day 1 of Week 12), and Visit 13 (any day of Week 14). 
4.7.4.2. Blood biochemistry 
Blood biochemistry is performed according to the standard procedure at a fasting state (8 
hours after the last meal including any sweat or alcohol drinks). 
The following variables are to be evaluated: 
− Glucose(mmol/L)  
− Bilirubin total(µmol/L)  
− Bilirubin indirect (µmol/L)  
− ALT (U/L)  
− AST (U/L)  
− GGT (U/L)  
− LDH (U/L)  
− Alkaline phosphatase 51 (U/L) 
− Total protein (g/L)  
− Creatinine (µmol/L) 
Volume of blood taken: 9 mL. 
Blood sampling is performed using standard procedures. 
Blood biochemistry is done at screening, Visit 6 (Day 1 of Week 1), Visit 10 (Day 1 of 
Week 8), Visit 12 (Day 1 of Week 12), and Visit 13 (any day of Week 14). Alkaline phosphatase 
is measured at screening only. 
 
4.7.4.3. Coagulation pattern 
Coagulation pattern is tested according to the standard procedure at fasting state (8 hours 
after the last meal). This study includes the following parameters: 
Prothrombin ratio (%) 
APTT (sec) 
 
51 Alkaline phosphatase is measured at screening only. 


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The volume of blood taken: 6 mL. 
Blood sampling is performed using standard procedures. 
Coagulation profile is done at screening, Visit 6 (Day 1 of Week 1), Visit 10 (Day 1 of Week 
8), Visit 12 (Day 1 of Week 12), and Visit 13 (any day of Week 14). 
 
4.7.4.4. Serology 
The test for HIV-infection means a qualitative assessment for HIV p24 antigen and HIV 
Ag/Ab Combo in serum or plasma.  
The test for syphilis is performed as a microprecipitation and direct hemagglutination assay 
(T. pallidum). Other tests can also be used. 
The presence/absence of HBV is assessed by testing the serum or plasma for HbsAg and 
for total anti-HBcor (IgG + IgM). If the HbsAg test results are positive, the patient cannot be 
enrolled in the study.  
If the patient is negative for HbsAg and positive for HBcor, a qualitative PCR for HBV 
DNA must be performed together with the test for anti-HBcor (IgG and IgM) and a consultation 
with an infectious disease specialist. 
Patients with positive anti-HBcor Ab results are eligible for the study if all of the following 
conditions are met:  
• Results of the qualitative PCR for HBV DNA are negative  
• Results of the test for anti-HBcor (IgG and IgM) are negative  
• No biochemistry abnormalities are found  
• Infectious disease specialists confirm the absence of hepatitis B (medical records must 
be sent to the Sponsor and retained in the source documents and Investigator’s File)  
• The Sponsor approves inclusion of this patient. 
The presence/absence of hepatitis C is assessed based on the results of the test for anti-
HCV antibodies (total IgM + IgG). If the patient is positive for anti-HCV antibodies, a qualitative 
PCR for HCV RNA and a consultation with an infectious disease specialist are required. 
Patients with positive anti-HCV Ab results are eligible for the study if all of the following 
conditions are met:  
• Results of the qualitative PCR for HCV RNA are negative  
• No biochemistry abnormalities are found  


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• Infectious disease specialists confirm the absence of hepatitis C (medical records 
must be sent to the Sponsor and retained in the source documents and Investigator’s 
File)  
• The Sponsor approves inclusion of this patient. 
 
All these tests are performed using routine procedures of the study site or central 
laboratory. To prepare for the tests, the patient should fast for 8 hours before blood drawing. 
The test is performed once, at screening52. 
The volume of blood taken: 12 mL. 
4.7.4.5. Urinalysis 
Urine sampling and urinalysis will be performed using standard procedures. Urinalysis 
included general properties of urine (color, clarity, specific gravity, pH, protein, and glucose) and 
urinary sediment microscopy (epithelium, erythrocytes, leukocytes, cylinders, bacteria, salts). 
Urinalysis is done at screening, Visit 6 (Day 1 of Week 1), Visit 10 (Day 1 of Week 8), Visit 
12 (Day 1 of Week 12), and Visit 13 (any day of Week 14). 
4.7.5. ECG 
A 12-lead ECG is recorded according to a standard procedure. 
ECG is taken at screening, Visit 6 (Day 1 of Week 1), and Visit 13 (any day of Week 14). 
4.7.6. Tuberculosis diagnostics 
This study will accept results of the Diaskintest® or QuantiFERON assays obtained with 
the standard procedures. Only Diaskintest® or QuantiFERON results obtained during the screening 
will be accepted. Diaskintest® or QuantiFERON test and their interpretations must be performed 
by a certified healthcare professional. 
The test is performed once, at screening. 
4.7.6.1. Skin test for tuberculosis 
Diaskintest® is a cutaneous TB test in this study. Diaskintest® is an intra-skin diagnostic 
test with a recombinant protein containing two antigens (ESAT6 and CFP10) of Micobacterium 
 
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tuberculosis and Micobacterium bovis, virulent strains of mycobacteria. The procedure and of 
Diaskintest® and results assessment are similar to those of the Mantoux test (PPD-L). The test is 
done with a thin needle, intradermally, into the middle third of the antebrachium. After 72 hours, 
the physician or nurse evaluates the response by measuring the transverse (with reference to the 
brachium axis) size of hyperemia and infiltrate (papula) in mm with a transparent ruler. Hyperemia 
is taken into account only if no infiltrate is seen. The following responses for the test can be seen 
(source http://www.diaskintest.ru/page_2.html): 
• 
Negative: no infiltrate or hyperemia. A “prick reaction” of up to 2 mm may be seen 
• 
Doubtful: hyperemia without infiltrate 
• 
Positive: infiltrate (papula) of any size. 
If the test result is doubtful, the patient can be enrolled after a negative QuantiFERON 
result is obtained or if additional requirements specified in section 4.7.6.3 are met. 
The Diaskintest® is a mandatory procedure for all enrolled patients. The only exception are 
patients who have contraindications to skin tests (e.g., patients have skin lesions in the middle of 
the inside forearm). Such patients should take the QuantiFERON test (plasma test for gamma 
immunoglobulins). 
The Diaskintest® is performed at a local TB dispensary or at the study site the qualified 
staff is available (materials will be provided by JSC BIOCAD). 
4.7.6.2. Plasma test for gamma interferon (QuantiFERON test) 
QuantiFERON test is recommended if skin tests cannot be performed (the patient has 
contraindications for skin tests, e.g., skin lesions in the middle of the inside forearm) or is the 
results of the Diaskintest® are uncertain. The QuantiFERON test allows evaluating plasma levels 
of the specific gamma interferon to confirm or exclude the tuberculosis infection. 
The procedure of the QuantiFERON test: 
Blood should be taken in the morning strictly at fasting state (or not less than 8 hours after 
the last food intake) into three vacuum test tubes from a QuantiFERON Assay Kit (positive 
control, negative control, test), with 1 mL of blood placed in each tube. The tubes with the blood 
must be kept at room temperature (+17°C to +25°C).  Do not refrigerate or freeze the blood 
samples. The tubes in the QuantiFERON Tubes pack must be delivered to the central laboratory 
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hours). The samples are shipped in an insulated container (tubes placed vertically) at a temperature 
from +17 to +25°С. 
At the laboratory, the tubes are incubated for 16-24 hours. During the incubation, 
lymphocytes recognize mycobacterial antigens. This recognition process includes the production 
of gamma interferon. The central laboratory performs ELISA to check the plasma for gamma 
interferon produced as an immune response to the antigens. 
For the QuantiFERON test, use only tubes from the QuantiFERON Assay Kit because each 
its tube contains a specific antigen. Do not use any tubes with the same colors but not from the 
QuantiFERON Assay Kit. 
Interpretation of QuantiFERON test results. Three options are available: Positive, negative, 
and doubtful. Doubtful results are possible due to the sensitivity to the tuberculosis antigen. If the 
test result is doubtful, the patient can be enrolled only if additional requirements specified in 
section 4.7.6.3 are met. 
4.7.6.3. Additional methods for tuberculosis diagnostics 
Patients with doubtful QuantiFERON results can be included in the study if all of the 
following requirements are met: A TB specialist excludes the TB infection (appropriate records must be 
sent to the Sponsor and retained in the source documents and Investigator’s File); the patient has no signs 
of active TB as confirmed by the chest X-ray performed any time within 1 month before randomization. 
If the Diaskintest®/QuantiFERON test could not be performed, the Mantoux test is allowed 
instead. The patients with uncertain or positive Mantoux test results are allowed in the study if the 
following conditions are met: A TB specialist excludes the TB infection (appropriate records must 
be sent to the Sponsor and retained in the source documents and Investigator’s File); the patient 
has no signs of active TB as confirmed by the chest X-ray performed any time within 1 month 
before randomization. 
4.7.7. Chest x-ray / fluorography 
Chest X-ray is performed with standard procedures of the study site to exclude tuberculosis 
or other lung diseases. Images are taken in the front view. If necessary, the Sponsor’s 
representative may request the images (if the subject develops active TB while in the study). 
The test is done at screening and on Visit 13 (Day 1 of Week 14). 


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Chest fluorography may be performed instead of the chest X-ray. Screening chest X-ray is 
not required if the patient has results of the chest X-ray/fluorography/CT/MRI performed within 1 
month before signing the informed consent. 
4.7.8. PASI and BSA assessment 
The area and severity of skin signs of psoriasis can be assessed with a PASI score. The 
form presented in Table 16 is used to assess the PASI score. 
Table 16. PSORIASIS AREA AND SEVERITY INDEX (PASI) 
 
The degree of the symptom: 
0-absent, 1–slight, 2–moderate, 3–severe, 4–extremely severe 
1 
Erythema 
Head 
and neck 
Trunk 
Upper 
extremities 
Lower extremities 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
2 
Induration 
Head 
and neck 
Trunk 
Upper 
extremities 
Lower extremities 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
3 
Desquamation 
Head 
and neck 
Trunk 
Upper 
extremities 
Lower extremities 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
0 
1 
2 
3 
4 
4 
Total 
 
 
 
 
Affected area, % 
5 
0: 0%, 1: < 10%, 2: from 10 to 29%, 3: from 30 to 49%, 4: from 50 to 69%, 5: from 70 to 89%, 6: 
from 90 to 100% 
6 
Affected area 
 
 
 
 
7 
Multiply the value in 
line 4 by the value in 
line 6 
 
 
 
 
8 
Weight of section 
×0.1 
×0.3 
×0.2 
×0.4 
9 
Multiply the value in 
line 7 by the value in 
line 8 
 
 
 
 
Total score (sum of the scores from all columns) 
 
Each symptom (erythema, induration, and desquamation) is assessed with a 4-score scale 
ranging from 0 (no symptoms) to 4 (max severity), separately for the skin of head and neck, body, 
arms and legs (lines 1-3). Assess the skin area mostly affected by the symptom. 


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Use the pictures below for PASI scoring (http://www.unhwamedi.com/Newsub02/Newsub05 a08.php ).  
 
Parameter  
None 
Mild 
Moderate 
Severe 
Extremely severe 
Erythema 
 
 
 
Score 
0 
1 
2 
3 
4 
Induration  
 
 
 
Score 
0 
1 
2 
3 
4 
Desquamation  
 
 
Score 
0 
1 
2 
3 
4 
 


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After that, scores are summarized (line 4).  
The area of skin affected by psoriasis is then estimated for each area. The area of skin 
affected by psoriasis is estimated with the palm rule. The area of the human palm without fingers 
corresponds to about 1% of all his/her skin. It is assumed that the skin of the head and neck 
corresponds to 10% of all skin area, trunk – to 30%, arms – to 20%, and legs – to 40%. 
Correspondingly, one palm corresponds to 10% of the skin on the head, 3.3% of the skin on the 
trunk, 5% of the skin on the upper extremities, and 2.5% of the skin on the lower extremities. 
To estimate the affected area from sections in scores, compare the affected area (%) from 
each section to line 5 of Table 16 and note the score in line 6. 
After that, multiply the value in line 7 by weight of respective section (0.1 for the head, 0.2 
for upper extremities, 0.3 for body and 0.4 for lower extremities).  
Summarize values in line 9 to receive the PASI score, which can vary from 0 (no rashes) 
to 72 (the most severe psoriatic process). 
The PASI score is calculated automatically when the investigator enters the following 
data in the eCRF: severity of erythema, induration, and desquamation in the evaluated body areas 
and the body surface area affected by psoriasis. The total PASI score and severity degree of 
individual symptoms of several localizations (lines 1-4 of Table 16) must be recorded in the source 
documents 
The body surface area affected by psoriasis is determined by the investigator at study 
visits and recorded in source documents and eCRF as a total body surface affected by psoriasis 
(%). The “palm” rule is used for assessment. 
Assessment is performed at screening, on Visit 8 (Day 1 of Week 4), Visit 10 (Day 1 of 
Week 8), and Visit 12 (Day 1 of Week 12). 
4.7.9. The sPGA assessment 
The severity of psoriasis is evaluated by the investigator using the scale explained below. 
The scale is used to assess the psoriatic lesions in a certain patient. Within each area, the severity 
is estimated by three criteria (induration, desquamation, and erythema). Not all three criteria may 
be present. Induration is considered the most resistant symptom, while the presence of 
desquamation or erythema can vary. In this case, the index is a sum of scores for infiltration of 
lesions and one of the prevailing criteria (erythema or desquamation). 
 






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Assessment is performed at screening, on Visit 8 (Day 1 of Week 4 ), Visit 10 (Day 1 of 
Week 8), and Visit 12 (Day 1 of Week 12). 
4.7.11. Psoriasis involvement of nails (NAPSI) 
Matrix involvement (pitting, leukonychia, red spots in the lunula, and nail plate 
crumbling) and/or nail bed involvement (onycholysis, nail bed hyperkeratosis, hemorrhages, “oil 
drops”) are assessed. The whole nail (the most affected one) is divided into quadrants. In each 
quadrant, the severity of nail matrix and nail bed involvement is assigned a score from 0 to 4. The 
sum of these two indexes (symptoms of the nail bed and matrix affection) is the total NAPSI score. 
The higher is NAPSI, the more severe are pathological changes in nails. The maximum score (8) 
corresponds to the total involvement of the nail plate. 
Table 20. Nail psoriasis severity index (NAPSI). 
Right hand: Nail matrix involvement  
(pitting, leukonychia, red spots, crumbling) 
0 — no symptoms, 1 — symptoms are present in one nail quadrant, 2 — symptoms are present in two nail quadrants, 3 — 
symptoms are present in three nail quadrants, 4 — symptoms are present in four nail quadrants. 
Nail of the little finger 
0 □      1 □      2 □      3 □      4□       
Nail of the ring finger 
0 □      1 □      2 □      3 □      4□       
Nail of the third finger 
 
0 □      1 □      2 □      3 □      4□       
Nail of the index finger 
0 □      1 □      2 □      3 □      4□       
Nail of the thumb 
0 □      1 □      2 □      3 □      4□       
Right hand: Nail bed involvement  
(onycholysis, subungual hyperkeratosis, hemorrhages, “oil drops”) 
0 — no symptoms, 1 — symptoms are present in one nail quadrant, 2 — symptoms are present in two nail quadrants, 3 — 
symptoms are present in three nail quadrants, 4 — symptoms are present in four nail quadrants. 
Nail of the little finger 
0 □      1 □      2 □      3 □      4□       
Nail of the ring finger 
0 □      1 □      2 □      3 □      4□       
Nail of the third finger 
0 □      1 □      2 □      3 □      4□       
Nail of the index finger 
0 □      1 □      2 □      3 □      4□       
Nail of the thumb 
0 □      1 □      2 □      3 □      4□       


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Left hand: Nail matrix involvement  
(pitting, leukonychia, red spots, crumbling) 
0 — no symptoms, 1 — symptoms are present in one nail quadrant, 2 — symptoms are present in two nail quadrants, 3 — 
symptoms are present in three nail quadrants, 4 — symptoms are present in four nail quadrants. 
Nail of the little finger 
0 □      1 □      2 □      3 □      4□       
Nail of the ring finger 
0 □      1 □      2 □      3 □      4□       
Nail of the third finger 
0 □      1 □      2 □      3 □      4□       
Nail of the index finger 
0 □      1 □      2 □      3 □      4□       
Nail of the thumb 
0 □      1 □      2 □      3 □      4□       
Left hand: Nail bed involvement  
(onycholysis, subungual hyperkeratosis, hemorrhages, “oil drops”) 
0 — no symptoms, 1 — symptoms are present in one nail quadrant, 2 — symptoms are present in two nail quadrants, 3 — 
symptoms are present in three nail quadrants, 4 — symptoms are present in four nail quadrants. 
Nail of the little finger 
0 □      1 □      2 □      3 □      4□       
Nail of the ring finger 
0 □      1 □      2 □      3 □      4□       
Nail of the third finger 
0 □      1 □      2 □      3 □      4□       
Nail of the index finger 
0 □      1 □      2 □      3 □      4□       
Nail of the thumb 
0 □      1 □      2 □      3 □      4□       
 
The NAPSI is used to assign a score to each nail, which can vary from 0 to 8. All 8 
components can be assessed for one target nail; in this case, the index can vary from 0 to 32. In 
this study, nail involvement will be assessed only for hands, so the total index of all nails can be 
from 0 to 80 (only hands). The Investigator should perform a complete assessment of hand NAPSI 
with questionnaires for recording scores for each nail. The total score is calculated automatically 
when data from the questionnaire are recorded in the eCRF. The score should be also recorded in 
the source documents. 
The test is done at screening and on Visit 12 (Day 1 of Week 12). 
4.7.12 Patient's assessment of pruritus 
The patient will assess itch severity with a visual analog scale, from 0 (no itch) to 100 
mm (unbearable itch). It is required that the patient fills the scale while at the study center during 


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the visit. The completed VAS is stored in the Investigator’s File; the score is recorded in the 
patient’s source documents. The Investigator records VAS results in the eCRF. 
Figure 6. An example of the visual analog scale for itch assessment. 
How severe is the itch you have now due to psoriasis? 
 
 
 
The test is done at screening, on Visit 1 (Day 1 of Week 0), Visit 6 (Day 1 of Week 1), 
Visit 8 (Day 1 of Week 4), Visit 10 (Day 1 of Week 8), and Visit 12 (any day of Week 12). 
4.7.13 Assessment the injection pain 
The study subject assesses how painful was the injection immediately after the injection 
and by filling out a special 10-score VAS (see below). It is required that the patient fills the scale 
while at the study center during the visit. Since the study drug is given as three injections, the 
patient will be asked to assess the most painful one. 
The completed VAS must be kept in the Investigator’s File; the score is recorded in the 
patient’s source documents. The investigator records the VAS score in the eCRF. 
No 
itch 
Unbearable itch 
0 
100 mm 


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Figure 7. Visual analogue scale for patient’s assessment of pain. 
Instructions: This scale shows how painful was the injection. The score 0 refers to no pain, the 
score10 refers to the highest, almost unbearable pain. 
 
Verbal description of 
pain 
No pain 
Mild 
pain 
Moderate 
pain 
Moderate 
pain 
Severe 
pain 
Worst pain 
possible 
Wong-Baker Faces 
 
 
 
 
 
 
Tolerance scale 
No pain 
Can be 
ignored 
Interferes 
with tasks 
Interferes 
with 
concentration 
Interferes 
with 
basic 
needs 
Bedrest 
required 
 
The assessment is performed on Visit 1 (Day 1 of Week 0), Visit 6 (Day 1 of Week 1), 
Visit 7 (Day 1 of Week 2), Visit 8 (Day 1 of Week 4), Visit 9 (Day 1 of Week 6), Visit 10 (Day 1 
of Week 8), and Visit 11 (Day 1 of Week 10). 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 


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4.7.20. Data entering to eCRF 
The principal investigator and the study team members will be provided logins and 
passwords to enter the eCRF system. 
Electronic CRF should be completed within 5 working days after the visit. All screening 
data should be entered at once after the screening.  
In the eCRF system, patients are identified only with their unique subject IDs. No screening 
IDs can ever be used in eCRFs.  
The screen failure data are not required to be entered in the eCRF. 
4.8. Stop rules and criteria for premature withdrawal for study subjects, study periods, and 
study as a whole 
4.8.1. Stop rules for study as a whole 
The study may be stopped in the following situations: 
1. By the decision of JSC BIOCAD due to safety reasons, ethical considerations, 
compliance issues, or any other reasons. 
2. By the decision of LECs or regulatory authorities. 
4.8.2. Criteria for premature withdrawal of study subjects 
The patient will be withdrawn from the study in the following circumstances: 
1. A major violation of inclusion/exclusion criteria is revealed after the patient was enrolled 


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in the study (withdrawn by the decision of JSC BIOCAD)54 
2. The patient recalls his/her consent to participate in the study 
3. The patient develops adverse events or serious adverse events, laboratory abnormalities or 
concomitant conditions that, in the investigator’s opinion, make further participation in the 
study impossible, dangerous or non-beneficial regarding patient’s well-being/safety 
4. The patient misses more than 2 infusions (in this case, patient’s removal must be approved 
by JSC BIOCAD, refer to section 6.5. Compliance Assessment) or misses 2 successive 
visits or 3 visits in total, or the patient regularly (3 times or more) violates the timing of the 
scheduled visits 
5. The patient gets pregnant. If pregnancy is suspected, the urine test for HCG must be 
performed. If the test shows a positive result, the patient must be withdrawn from the study 
(follow-up procedures are described in section 5.4) 
6. The patient has a major depressive disorder, suicidal ideation or attempts  
7. The study is terminated by the decision of JSC BIOCAD, local ethics committees, or 
regulatory authorities 
8. The patient uses medications prohibited by the Protocol 
9. The patient dies. 
The investigator must inform JSC BIOCAD within 24 h about a patient’s premature 
withdrawal and specify the reason. 
If the subject discontinues the study, an Early Withdrawal Form in the CRF should be filled 
out. The follow-up procedures for the discontinued subjects are described in section 5.4 
Procedures by visits. 
Subjects who were prematurely withdrawn due to safety reasons are not to be replaced. 
See section 11.5 for further details. Study termination. 
4.9. Drug accountability  
The investigator is responsible for the test drug/placebo accountability at the trial site. 
Throughout the study, the investigator must ensure proper accountability of the investigational 
product as required by regulatory authorities. The investigator must maintain accurate records 
regarding the receipt of the investigational product from JSC BIOCAD, its dispensing to study 
subjects and return to JSC BIOCAD.  
 
54 Violations of inclusion/exclusion criteria justified by the Investigator and approved by the Sponsor cannot be a 
reason to withdraw the patient from the study. 


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When the investigator or the pharmacist receives the investigational product, he/she should 
check the delivery, sign and date a receipt form and documentation provided by JSC BIOCAD, 
and return it to JSC BIOCAD. A copy of this documentation must be stored in the Investigator 
File. 
The amount of investigational product delivered to the study site must be recorded in the 
receipt form provided by JSC BIOCAD. This form will be used as an investigational product 
accountability record. 
Accurate accountability records should be available to the Monitor during each monitoring 
visit. Drug accountability records should include: 
• Confirmation of delivery of the investigational product to the study site 
• Inventory at the study site 
• Use of investigational product by each study subject 
• Return of unused drug product to JSC BIOCAD. 
Records should include dates, amounts, batch numbers, and expiry dates of the 
investigational product (if applicable). The investigator must maintain accountability records to 
ensure that: 
• Study subjects get the investigational product at doses specified by the 
Protocol/Amendment 
• The total amount of the investigational product provided by JSC BIOCAD is accurately 
checked and delivered undamaged. 
Unused investigational product must not be used for any other purpose except this study.  
The Monitor from JSC BIOCAD will regularly inspect accountability records. 
4.9.1. Handling of investigational products 
The test drug/placebo delivered to the study site should be stored 2°С to 8°С, protected 
from light. All medicinal products supplied by the Sponsor must be stored in a limited access area. 
Only the principal investigator, co-investigators, and an authorized representative of the site 
administration will have access to the storage area.  
The investigational product may be stored only at the study sites authorized for this clinical 
trial. The investigator must ensure safe storage of the investigational drug to prevent loss, theft, or 
improper environmental conditions (temperature) specified by the Sponsor and described in the 
Investigator Brochure. The investigator must maintain a temperature log. 


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4.10. Procedure for keeping and unblinding randomization codes 
As this study is double-blind, the study product and placebo will be identified only by the 
patient-specific lot number. JSC BIOCAD will prepare a few envelop kits with therapy arm codes 
(i.e. with lot numbers corresponding to the test product/placebo). One of these envelop kits will be 
stored at JSC BIOCAD; another will be given to the principal investigator of every study center 
and stored in the Investigator's File. 
The investigator is allowed to unblind the treatment only in case of an emergency. The 
investigator must exercise his/her best efforts to prevent the loss or unblinding of study codes when 
unnecessary. 
Treatment can be unblinded only in case of an emergency when this is necessary to give 
an appropriate treatment to the patient and ensure his/her well-being. If a medical situation that 
requires unblinding occurs, the principal investigator must contact a representative from JSC 
BIOCAD: medical expert, pharmacovigilance officer, or clinical study manager (for contact 
details see the title page), specify unblinding reasons and obtain consent to this procedure. If JSC 
BIOCAD approves unblinding, the investigator unblinds the code, records this fact in the source 
document, and notifies the clinical study manager by phone or e-mail. 
All patients participating in the study will receive Subject ID cards containing the protocol 
code, study site number, investigator’s contact information, contact information of the BIOCAD’s 
responsible medical officer and pharmacovigilance officer (available 24 h daily). Patients should 
know that they should have their study subject’s cards all the time with them and notice medical 
personnel of any other medical facility about their participation in this clinical study. If necessary 
(for example, to administer another medicinal product), a physician of another medical facility 
(other than the study center) can contact the Investigator to discuss benefit or possible risks related 
to concomitant therapy. 
4.11. Data entered directly into CRF (i.e. no prior written or electronic record of data) and 
considered as source data 
All data entered to the CRF must be recorded in the source documentation. 
In this study, no data will be entered directly to the CRFs without prior entering to the 
source documents. 
 
 


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5. ELIGIBILITY AND EXCLUSION OF STUDY SUBJECTS 
5.1. Inclusion criteria 
1. Signed informed consent form 
2. Age of 18 to 65 years inclusive 
3. Plaque-type psoriasis, moderate to severe, stable for at least 6 months at the time of inclusion 
in the study (i.e. no changes in the morphological signs of psoriasis, no significant worsening 
or exacerbations were seen during this period, as judged by the investigator) 
4. Patients received at least one course of phototherapy or systemic therapy55 for psoriasis or are 
candidates56 for such treatment according to the investigator 
5. At screening, body surface area (BSA) affected by plague psoriasis of 10% or greater, PASI 
score of 12 or greater, and an sPGA score of 3 or greater 
6. Treatment failure or unbearable toxicity with /contraindications for TNFα inhibitors or other 
biologics (monoclonal antibodies or their fragments) administered for at least 3 months. If such 
patient is included in the study, the treatment must be stopped at least 12 calendar days before 
signing the informed consent 
7. Laboratory values at screening: 
− Hemoglobin ≥ 9 g/dL (90 g/dL) 
− WBC ≥ 3 000/µL (3.0×109/L) 
− Platelets ≥ 100 000/µL (100×109/L) 
− Neutrophils ≥ 2 000/µL (2.0×109/L) 
− AST, ALT, and alkaline phosphatase ≤ 2.5 ULN 
− Serum creatinine < 176.8 µmol/L (2.0 mg/dL) 
− The negative test result for serologic and virologic markers for active/latent hepatitis B 
(HBV) and hepatitis C (HCV). 
8. Negative pregnancy urine test in female subjects (no test is required in women who are post-
menopausal for at least 2 years and in surgically sterile women) 
9. No history of tuberculosis 
 
55Systemic therapy refers to any non-biologics (methotrexate, cyclosporine, acitretin, etc.), or biologics (TNF 
inhibitors, anticytokine drugs, anti-CD20 drugs, etc.) 
56BCD-085 is planned to be used as either first- or second-line treatment, so the study involves treatment-naive 
patients along with those who failed to respond to systemic or phototherapy. 


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10. Negative Diaskintest® results57 or negative QuantiFERON test results58 
11. Patients with uncertain Diaskintest® results are eligible for the study if they show negative 
results with QuantiFERON test. Patients with uncertain QuantiFERON test are eligible for the 
study if a qualified specialist confirms no TB infection (a written report must be provided) and 
the chest X-ray exam performed within 1 month before randomization reveals no signs of 
active TB infection 
12. No history of or current alcohol or drug abuse at baseline 
13. The patient must be able to follow the Protocol procedures (in the investigator’s opinion) 
14. Patients of childbearing potential and their partners with preserved reproductive function must 
consent to practice reliable contraceptive starting from 2 weeks before inclusion in the study 
and for 4 weeks after the last dose of screening to 4 weeks after the last dose of the study drug. 
This requirement does not apply to you if you have undergone surgical sterilization. Reliable 
contraception means one barrier method in combination with one of the following: spermicides 
or intrauterine device / oral contraceptives used by the subject’s partner. 
5.2. Exclusion criteria 
1. Baseline erythrodermic, pustular, and guttate psoriasis, drug-induced psoriasis, or any other skin 
diseases (e.g. eczema) that can affect/complicate the assessment of psoriasis treatment.  
2. Concomitant therapy: 
− Prior use of monoclonal antibodies targeting IL17 or its receptor 
− Prior use of two or more TNFα-inhibiting monoclonal antibodies or their fragments 
− Prior use of two or more monoclonal antibodies against other targets 
− Prior use of monoclonal antibodies within 12 weeks before signing the informed 
consent 
− Oral glucocorticoids >10 mg (equivalent to prednisolone) during 4 weeks prior to 
signing the informed consent and throughout entire screening period; oral 
glucocorticoids ≤10 mg/day if the dose was not stable for 4 weeks prior to signing the 
informed consent and through the entire screening period 
 
57If Diaskintest®/QuantiFERON test cannot be performed, the Mantoux test can be done instead. The patients 
with uncertain or positive Mantoux test results are allowed in the study if the following conditions are met: a qualified 
specialist excluded TB infection (a written report must be provided) and the chest X-ray exam performed within 1 
month before randomization revealed no signs of active TB infection. 
58QuantiFERON test is recommended if skin tests cannot be performed (skin lesions in the middle of the inside 
forearm). 


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− Use of systemic non-biologics including methotrexate, sulfasalazine, cyclosporine, and 
acitretin within 4 weeks before randomization. This was an exclusion criterion if doses 
of said drugs were not stable for 4 weeks before signing the informed consent and 
during the entire screening period. If prior systemic therapy with non-biologics was 
stopped due to any reasons, the screening period could be extended up to 8 weeks 
during which no new non-biologics were allowed 
− Phototherapy (including selective UCB phototherapy and PUVA therapy) within 4 
weeks before randomization 
− Live or attenuated vaccines administered at any time during 8 weeks before screening 
3. Recurring, chromic or any other active infection if the investigator considers that the study drug 
can harm the patient 
4. Documented HIV-infection or a history of a severe immunodeficiency of any origin 
5. Positive screening results for Hbs-antigen, hepatitis B core antibodies (anti-HBc Ab)59 and/or 
hepatitis C antibodies60 
6. Current/history of tuberculosis 
7. Current or a history of herpes zoster61 
8. Positive results of microprecipitation reaction together with positive TPHA assay results at 
screening 
9. Concurrent diseases ongoing at screening that may increase the risk of adverse events during 
the study or affect the evaluation of psoriasis symptoms (mask, enhance or alter the symptoms of 
psoriasis, or cause clinical or laboratory signs/symptoms similar to those of psoriasis): 
− active inflammatory diseases or aggravation of chronic inflammatory diseases other than 
psoriasis 
− Stable angina class III-IV, unstable angina or a history of myocardial infarction within 1 year 
before signing the informed consent 
− Moderate to severe cardiac insufficiency (NYHA classes III and IV) 
 
59Patients with positive anti-HBc Ab results are eligible for the study if all of the following conditions are met: 
negative qualitative PCR results for HBV DNA (this test is performed only if anti-HBV antibodies were detected); 
blood test results available for anti-HBc IgG and anti-HBC IgM; no abnormalities found in blood biochemistry; 
medical infections specialist provides a documented conclusion that the patient has no HBV; and the Sponsor approves 
enrollment of this particular patient. 
60Patients with positive anti-HBC Ab results are eligible for the study if all of the following conditions are met: 
negative qualitative PCR results for HCV DNA (this test is performed only if anti-HBC antibodies were detected); no 
abnormalities found in blood biochemistry; medical infections specialist provides a documented conclusion that the 
patient has no HCV; and the Sponsor approves enrollment of this particular patient. 
61 No additional test for antibodies to varicella-zoster virus are required. The decision is based on clinical signs 
and medical history. 


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− Severe treatment-resistant hypertension62 
− A history of atopic asthma or angioedema; 
− Moderate to severe respiratory failure, COPD grade 3/4 
− Decompensated 
diabetes 
mellitus, 
decompensated 
hypothyroidism, 
decompensated 
hyperthyroidism 
− Systemic autoimmune diseases (including lupus erythematosus, rheumatoid arthritis, 
ankylosing spondylitis, Crohn/s disease, ulcerative colitis, systemic sclerosis, inflammatory 
myopathies, mixed connective tissue disease63, intersection syndrome, etc.) 
− Any other concurrent diseases (including but not limited to metabolic, hematologic, hepatic, 
renal, pulmonary, neurological, endocrine, cardiac, gastrointestinal, and infectious diseases) 
that may affect the course of psoriasis, affect the assessment of signs/symptoms of psoriasis, 
or put patients using the study treatment at additional risk 
10. Malignancies within the past 5 years (other than adequately treated (cured) squamous or basal 
cell carcinoma, cervical cancer in situ or ductal carcinoma in situ) 
11. Known severe allergies (anaphylaxis or multiple drug allergy) 
12. Known allergy or intolerance to monoclonal antibody drugs (murine, chimeric, humanized, or 
human) or any other components of the study drug 
13. Major surgery within 30 days before the screening, or a major surgery being scheduled at any 
time during the study 
14. 
Severe 
infections 
(including 
those 
requiring 
hospitalization 
or 
parenteral 
antibacterial/antimycotic/antiprotozoal treatment) within 6 months before the first dose of the 
study drug; 
15. Systemic use of antibacterial/antimycotic/antiprotozoal drugs within 2 months before the first 
dose of the study drug 
16. More than 4 episodes of respiratory infection within 6 months before screening 
17. A history of epileptic attacks or seizures 
18. The patient cannot stop phototherapy (including UVB and PUVA therapy) for psoriasis 
19. Any concurrent diseases during which, in the investigator’s opinion, the study treatment can 
harm the patient 
20. Pregnancy, breastfeeding or planning for pregnancy while participating in the study 
 
62Treatment-resistant arterial hypertension is defined as blood pressure above the target range despite the 
concurrent use of three anti hypertensive drugs of different classes, including a diuretic, and non-medication methods 
(salt-free diet, controlled physical exercise). 
63 Signs/symptoms of psoriatic arthritis are not considered an exclusion criterion. 


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21. Any psychiatric disorders, including a history of major depression and/or suicidal thoughts that 
can, in the investigator’s opinion, put the patient at risk or affect patient’s ability to follow the 
study protocol 
22. Patients with the existence of or history of abuse of recreational drugs, prescription drugs, 
alcohol, or any other psychoactive substances 
23. Participation in any other clinical study within 3 months before screening or simultaneous 
participation in other clinical studies 
24. Patients who were randomized to this study and then discontinued the study due to any reasons 
(i.e. patients who met all other inclusion/exclusion criteria), were not re-enrolled in this study. 
5.3. Withdrawal criteria 
The patient will be withdrawn from the study in the following circumstances: 
1. A major violation of inclusion/exclusion criteria is revealed after the patient was enrolled 
in the study (withdrawn by the decision of JSC BIOCAD)64 
2. The patient recalls his/her consent to participate in the study 
3. The patient develops adverse events or serious adverse events, laboratory abnormalities or 
concomitant conditions that, in the investigator’s opinion, make further participation in the 
study impossible, dangerous or non-beneficial regarding patient’s well-being/safety 
4. The patient misses more than 2 infusions (in this case, patient’s removal must be approved 
by JSC BIOCAD, refer to section 6.5. Compliance Assessment) or misses 2 successive 
visits or 3 visits in total, or the patient regularly (3 times or more) violates the timing of the 
scheduled visits 
5. If the patient gets pregnant. In case of a suspicion for pregnancy, the urine test for HCG 
should be performed. In case of a positive result, the patient is to be withdrawn from the 
study 
6. The patient has a major depressive disorder, suicidal ideation or attempts  
7. The study is terminated by the decision of JSC BIOCAD, local ethics committees, or 
regulatory authorities 
8. The patient uses medications prohibited by the Protocol 
9. The patient dies. 
The investigator must inform JSC BIOCAD within 24 h about a patient’s premature 
withdrawal and specify the reason. 
 
64 Violations of inclusion/exclusion criteria justified by the Investigator and approved by the Sponsor cannot be a 
reason to withdraw the patient from the study. 


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5.4. Follow-up of subjects withdrawn from the study or subjects who discontinued the study 
treatment but remain in the study for follow-up 
5.4.1. Follow-up of patients who received at least one dose of BCD-085/placebo 
The following should be done if the patient who received at least one injection of BCD-
085/placebo discontinues the study early: 
- The Early Withdrawal Visit should be performed at the day of withdrawal with the Early 
Withdrawal Form being filled out. AEs/SAEs must be registered during this visit, while the amount 
of other examinations is to the discretion of the investigator. 
If the subject discontinues the study due to an AE/SAE, the investigator should conduct 
further treatment and follow-up after the Early Withdrawal Visit in accordance with the study site 
standards for the treatment of a certain AE/SAE. The patient should be followed up until the AE 
or SAE resolves completely. 
The woman who discontinues the trial because of pregnancy should be monitored through 
the entire pregnancy and for 6 months after delivery to evaluate the mother’s and child’s health. 
Information on pregnancy course and outcome should be recorded in the source documents (after 
the patient provides her consent). During the whole period of pregnancy, the investigator in 
collaboration with the attending Ob/Gyn specialist should monitor the patient’s overall health, the 
course of pregnancy, and laboratory values including ultrasound. When the child is born, the 
investigator together with the attending pediatrician should monitor the newborn for 6 months 
evaluating the child’s clinical status and the laboratory/instrumental findings. 
Information regarding the health state of all dropouts should be recorded in their source 
documentation and CRFs. 
5.4.2. Follow-up of subjects who did not receive a single dose of BCBD-085/placebo 
If the subject discontinues the study before dosing, the Early Withdrawal Form should be 
filled out on the day of withdrawal. Non-dosed patients are followed-up only if they discontinue 
the study because of AEs/SAEs. In this case, the follow up is performed according to the study 
site standards. 
If the subject withdraws from the study due to any reason after receiving a dose of the test 
drug/comparator, his/her data will be included in the analysis. If the subject withdraws from the 
study before dosing, his/her information will be removed from the analysis. 


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6. TREATMENT OF STUDY SUBJECTS 
6.1. Study therapy 
In this study, BCD-085 will be administered to patients in three of four study arms. Patients 
will receive 40 mg, 80 mg, or 120 mg BCD-085 as SC injections once weekly for the first three 
weeks (induction regimen) and then once every two weeks (maintenance regimen). Thus, the drug 
will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction period), 
Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10 (maintenance period). 
For blinding purposes, patients from 40 mg and 80 mg arms will receive two or one SC 
injection of placebo (1 mL each), respectively. 
Patients in the control arm will receive 3 SC injections of placebo (each injection is 1.0 mL). 
Placebo to be used has the similar composition for all three arms and contains the same excipients 
that the BCD-085 dosage form. 
Regardless of the arm to which the patient is assigned, injections will be performed by an 
authorized site medical nurse directly in the study site. Injections can be given to the abdomen, 
hips, or upper arms. Injections should be given at least 5 cm apart. 
During the entire study period, patients are not allowed to use phototherapy (UV-B), 
photochemotherapy (PUVA), biologics other than BCD-085, and live or attenuated vaccines. 
The patients can use systemic non-biologic therapies (methotrexate, sulfasalazine, 
chlorambucil, leflunomide, cyclosporine A, azathioprine, aromatic retinoids (acetretin), and 
glucocorticoids (> 10 mg of prednisolone equivalent per day) if their dose was stable for 4 weeks 
before signing the informed consent and through the entire screening period) Patients are not 
allowed to change their systemic non-biologic treatment during the study, increase the dose, or 
add any new medications of this category. Patients are allowed to discontinue systemic non-
biologic therapies only if he/she has any life- or health-threatening adverse effects due to this 
treatment. Any modifications of the dosing regimen or dose reduction for systemic non-biologic 
therapy can be made only after reconciliation with the Sponsor. 
The patients may use topical glucocorticoids on the face, underarm, and genitals. The 
patients may use topical moisturizing products, emollients, oils or salicylic acid-based products if 
necessary. The patients should discontinue all local skin products (medications or cosmetics) 24 
hours before the planned PASI assessment. 


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6.1.1. Preparation of the investigational products for administration and administration 
procedure 
6.1.1.1. Test drug and placebo 
Injections will be given at the study site by the investigator or an authorized nurse (a 
member of the study team). 
 
Since several SC injections were given at once, it was preferred to use the same area with 
two injection sites being at least 5 cm apart. Multiple injections should be performed within 15 
minutes. The time for PK blood drawing is counted from the last injection. 


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6.1.2. Adjustment and discontinuation of study therapy 
6.1.2.1. Dose modification and discontinuation of the study drug 
No dose modifications for the study drug are allowed in this study. If the investigator 
decides that further treatment / participation in the study does not meet the best patient’s interests, 
this patient may be withdrawn from the study. 
6.1.1.1.1. Follow-up for toxicity 
In case of temporary or permanent therapy discontinuation, the patient should be followed 
up until the resolution or stabilization of the event. If the therapy is suspended for more than 14 
days, it should be discontinued permanently. However, if the investigator and the Medical Expert 
believe that the patient who discontinued the drug for more than 14 days may get benefit from the 
therapy, the study treatment may be continued.  
To reveal AEs and SAEs, all patients will be followed up for 28 days from the last dose of 
BCD-085/placebo. 
6.1.3. Overdose 
6.1.3.1. Overdose with study drug 
No overdose events has been described with BCD-085. Effects of BCD-085 injected at 
single doses higher than 3 mg/kg are not known. If an overdose is registered in this study, and the 
patient develops some adverse events related, in the investigator’s opinion, to the overdose, further 
treatment should be given at the discretion of the attending physician. No antidote is available, so 
appropriate symptomatic treatment should be applied. 
6.2. Concomitant therapy, medications allowed and prohibited by the Protocol 
6.2.1. Allowed concomitant therapy 
The patients can use systemic non-biologic therapies (methotrexate, sulfasalazine, 
chlorambucil, leflunomide, cyclosporine A, azathioprine, aromatic retinoids (acetretin), and 
glucocorticoids (> 10 mg of prednisolone equivalent per day) if their dose was stable for 4 weeks 
before signing the informed consent and through the entire screening period) Patients are not 
allowed to change their systemic non-biologic treatment during the study, increase the dose, or 
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biologic therapies only if he/she has any life- or health-threatening adverse effects due to this 
treatment. Any modifications of the dosing regimen or dose reduction for systemic non-biologic 
therapy can be made only after reconciliation with the Sponsor. 
The patients may use topical glucocorticoids on the face, underarm, and genitals. The 
patients may use topical moisturizing products, emollients, oils or salicylic acid-based products if 
necessary. The patients should discontinue all local skin products (medications or cosmetics) 24 
hours before the planned PASI assessment. 
6.2.2. Prohibited concomitant therapy 
Treatments prohibited in this study: 
✓ Biologics (including other anti-IL-17 monoclonal antibodies, TNFα inhibitors, anti-
cytokine agents, anti-CD20 agents, etc.) 
✓ New systemic non-biologics or dose modification for already used systemic non-
biologics65 
✓ Systemic66 glucocorticoids (except for < 10 mg/day of prednisolone equivalent if the 
dose was stable for 4 weeks before signing the informed consent) 
✓ Phototherapy [including selective phototherapy (UVB) and photochemotherapy 
(PUVA)] 
✓ Any unauthorized products other than BCD-085 
✓ Opioid analgesics 
✓ Vaccines. 
The study participant who received or needs any prohibited treatment must be withdrawn 
from the study. 
6.3. Compliance with study procedures 
In this study, the information will be documented about each administration of the 
investigational product, doses, and intervals between the study visits.  
The Clinical Research Associate (CRA) will inspect the study documentation during 
monitoring visits and upon completion of the study. 
 
65No dose increase was allowed for systemic non-biologics. Any modifications of the dosing regimen or dose 
reduction for systemic non-biologic therapy can be made only after reconciliation with the Sponsor. 
66 Doses > 10 mg were allowed in the active study period if glucocorticoids were used parenterally to manage 
emergencies such as angioedema, anaphylactic shock, and other types of shock. 


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6.3.1. Compliance assessment 
Non-compliance criteria (the patient must be removed from the study): 
- The patient misses more than 2 injections of the study drug (removal has to be reconciled 
with JSC BIOCAD) 
- The patient misses >2 sequential visits or a total of 3 visits in the study 
- The patient regularly violates the visit schedule (>3 violations) 
- During the first month of treatment, all patients except for those included in the PK 
population are allowed to re-schedule the visit within 7 days for any reasons (if re-scheduling the 
visit when the test drug/placebo is to be injected, all subsequent visits must be re-scheduled 
accordingly). 
- For patients in the PK population, visits 1-6 can be re-scheduled within 7 days only due 
to AEs/SAEs; visits 7 and 8 can be re-scheduled within 7 days due to any reasons. If the visit 
during which BCD-085/placebo is to be given is re-scheduled, all subsequent visits must be re-
scheduled accordingly. 
- Visit 9 and subsequent visits are allowed for re-scheduling within 14 days due to any 
reason. If the visit during which BCD-085/placebo is to be given is re-scheduled, subsequent visits 
must re-scheduled accordingly. 
 
7. EFFICACY EVALUATION 
7.1 List of efficacy variables 
7.1.1. Definition of variables 
The patient is considered a PASI75 responder if the PASI score improves by 75% from 
baseline. PASI50 and PASI90 responders are defined in the same way. 
7.1.2. Efficacy endpoints 
Primary endpoints 
• The proportion of patients in each study arm who achieved a PASI 75 at Week 12 
of treatment. 
 


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7.1.3. Secondary endpoints 
• The proportion of patients in each study arm who achieved a PASI 75 at weeks 4 
and 8 of treatment 
• The proportion of patients in each study arm who achieved a PASI 50/90 at weeks 
4, 8, and 12 of treatment 
• The relative PASI score improvement from baseline at weeks 4, 8, and 12, by study 
arms 
• The relative BSA improvement from baseline at weeks 4, 8, and 12, by study arms 
• The relative NAPSI improvement from baseline at weeks 4, 8, and 12, by study 
arms 
• The mean change from baseline in the intensity of pruritus measured by VAS (0-
100 mm) at weeks 1, 4, 8, and 12, by study arms 
• The proportion of patients in each study arm who achieved an sPGA score 0 or 1 
at weeks 4, 8, and 12 relative to baseline 
• The mean change from baseline in the QoL score in each study arm (assessed using 
the DLQI and SF-36 scales) at weeks 4, 8, and 12. 
7.2 Methods and timeframes for assessment, documenting, and analysis of immunogenicity 
variables 
7.2.1 Timeframes for analysis of efficacy variables 
The efficacy analysis by the primary endpoint (PASI75) will be performed after 12 weeks 
of blinded therapy with BCD-085/placebo. 
The timing of the efficacy assessment with the secondary endpoints is specified in section 
7.1. List of efficacy variables. 
7.2.2 Methods and timeframes for assessment and documenting of efficacy variables 
Per protocol, the efficacy analysis is to include all patients who received at least one dose 
of BCD-085/placebo and who attended at least one visit next visit. If no data are available at Week 
12, the data from the last assessment are to be used (last-observation-carried-forward method). In 
addition, these patients should be considered non-responders and analyzed separately. 


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8. SAFETY ASSESSMENT 
8.1 List of safety endpoints 
8.1.1 Definitions 
8.1.1.1. Adverse events 
Adverse Event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have 
to have a causal relationship with this treatment. 
An adverse event (AE) can, therefore, be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not related to the medicinal product: from treatment initiation 
through 28 days after patient withdrawal from the clinical study. 
8.1.1.2. Serious adverse events 
Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalization or its prolongation 
• 
Results in persistent or significant incapacitation or disability 
• 
Is a congenital anomaly or birth defect. 
In case of any uncertainty whether the event meets the seriousness criteria or not, it should 
be treated as as a serious adverse event. 
An immediate risk of death from a reported event is considered life threatening. A life-
threatening event does not include an adverse event that, had it occurred in a more severe form, 
might have caused death, but is not associated with an immediate risk of death in the form it 
occurred. For example, hepatitis resolved without signs of hepatic insufficiency will not be 
considered life threatening in spite of the fact that more severe hepatitis can lead to fatal outcome. 
Similarly, an allergic reaction resulting in face angioedema will not be considered life threatening, 
although larynx angioedema, allergic bronchospasm or anaphylaxis can lead to fatal outcome. 
Hospitalization is an official admission to the hospital. Hospitalization or its prolongation 
is a criterion of AE seriousness; however, hospitalization itself is not a serious adverse event. 
Hospitalization or its prolongation not associated with an AE should not be reported by the 


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investigator as a serious adverse event. This is applicable (including but not limited) to the 
following cases: 
• Hospitalization or prolongation of existing hospitalization is necessary to perform 
procedures required by the Protocol. 
• Hospitalization or prolongation of existing hospitalization is a part of routine 
procedures in this study site (for example, stent removal after a surgery). An 
appropriate confirmation should be kept in a study file. 
• Hospitalization due to a pre-existing condition, which did not aggravate. 
Disability is a significant impairment of the patient's ability to live a normal life. 
Other reportable information. Certain information not considered an SAE must be 
recorded, presented in the report, and followed up as an SAE. This includes:  
• The use of the investigational product during pregnancy. If the pregnancy is 
confirmed, the study therapy should be discontinued immediately. 
• The use of the investigational product during breast-feeding, regardless of AE 
development.  
• An overdose of the study drug as defined in the Protocol, whether or not it was 
associated with an AE.  
• Unintentional or accidental use of the investigational product, whether or not 
considered related to an AE. 
• Medication errors whether or not considered related to an AE (including 
confusion or possible confusion during the administration of investigational 
products). 
• Death whether or not associated with an AE. 
8.1.1.3. Unexpected adverse events 
The unexpected adverse reaction is an adverse reaction, the nature or severity of which 
is not consistent with the applicable product information (e.g., Investigator's Brochure for an 
unapproved investigational medicinal product). 
8.1.2. Safety endpoints 
• The proportion of patients who develop SAEs 
• The proportion of patients who develop AEs  
• The proportion of patients who develop administration site reactions 


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• The proportion of patients who develop grade 3/4 AEs/SAEs 
• The proportion of patients who discontinued the study due to AEs/SAEs. 
8.2. Methods and timeframes for assessment, documenting and analysis of safety variables 
8.2.1. Timeframes for analysis of safety variables 
The safety endpoints will be analyzed upon completion of the dosing with BCD-
085/placebo and follow-up. 
8.2.2. Methods and timeframes for assessment and documenting of safety variables 
The safety analysis will include all patients who received at least one dose of the 
investigational product. Additionally, the SAE analysis will include all randomized patients 
starting from the ICF signing and until the end of their participation in the study. 
Safety will be analyzed based on the information about 
- AEs/SAEs; 
- Physical examination findings and vital signs 
- CBC and biochemistry results, urinalysis results, and coagulation pattern. 
- ECG. 
The frequency of these procedures is specified in section 4.6.1 Study schedule (visits and 
procedures). AEs/SAEs will be recorded in accordance with the guide provided by the Sponsor. 
The investigator is responsible for recording adverse events in the clinical study. 
AEs must be captured starting from the first dose of the investigational product and through 
4 weeks after the last dose. AEs related to the protocol procedures must be recorded from the 
moment the subject signed the ICF. SAEs must be captured from the moment the patient signed 
the ICF and through 4 weeks after the last dose of the investigational product. The study 
investigator can report SAEs that occurred after the required follow-up if he/she considers them 
related to the investigational product or study procedures.  
The study investigator must document non-serious AEs in the source documents and in the 
CRF, and present them to the CRA at the next monitoring visit. SAEs must be reported to the 
Sponsor immediately (within 24 hours). Reports must be submitted to the Sponsor immediately 
(within 24 hours) by fax 
 
 
 
 
 
 
 
 
 put “To Pharmacovigilance Officer” in the subject field). 


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The investigator should receive a receipt/delivery confirmation. Information regarding unexpected 
adverse reactions must be presented to the CRA at the next scheduled visit. 
8.3 Requirements for reports. Documenting and reporting AEs and completing AE Report 
Forms 
8.3.1. Documenting AEs/SAEs 
At every visit, a record must be made whether or not any AEs occurred during the period 
from the previous visit. Any adverse event reported for a patient since he/she signed the ICF must 
be recorded in source documents and in an Adverse Event Report Form (in the CRF). AEs will be 
documented in accordance with the Manual provided by the Sponsor. 
AEs should be recorded and numbered consecutively as they occur. Each AE is reported 
in an AE Reporting Form. Rules for reporting AE/SAE are described in details in the Sponsor’s 
guide. 
Adverse events must be recorded regardless of their seriousness and causal relationship 
with the study therapy. If an adverse event re-emerges, it must be recorded as a new AE and 
assigned a new number. 
Laboratory/vital sign abnormalities 
Laboratory/vital sign abnormalities considered to be adverse events (assessed as clinically 
meaningful, including those of CTCAE 4.03 grade 1, inducing clinical symptoms or complaints 
requiring concomitant therapy or changes in study therapy) should be recorded in the CRF, 
Adverse Events section. It is preferable to specify diagnosis rather than individual symptoms (for 
example, anemia instead of reduced hemoglobin). Laboratory abnormalities meeting the criteria 
of adverse events should be followed up until they return to a normal or adequate explanation is 
obtained.  
8.3.2. AE/SAE reporting 
The AE Report Form should be filled out during the study visit (or the investigator can do 
it later the same day), except for data not available/not known at that moment. All sections of the 
form must be filled out. If the data are not available, the following should be entered: "Data not 
available" or "N/A”. However, all actions should be taken to receive all necessary data on 
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The following information is recorded in source documents and the AE Report Form of the 
CRF: 
- AE No. as it occurred 
- Visit No. 
- A brief description of the AE 
- Seriousness (yes/no) 
- Seriousness criterion 
- CTCAE 4.03 grade 
- Onset date 
- Date of resolution (return to normal or baseline) 
- Outcome 
- Actions taken due to the AE 
- Causal relationship with the study drug (BCD-085/placebo) 
- Comments specifying any clinically relevant (in the investigator’s opinion) information 
related to AE development or therapy. 
If a medication therapy is administered, its components should be described in section 
“Concomitant therapy” of the CRF, with a notice that a medication was used to manage the AE. 
Columns Grade, Outcome, Measures, and Causal Relationship should be filled using 
digital codes explained in the Notes section. If the investigator considers an AE to be an SAE, 
he/she must fill out an SAE Report Form in addition to an AE Report From (printed copies). 
One SAE Report Form is filled out for one SAE. If the AE remains unresolved at the next 
visit, the checkbox in AE section of the eCRF should be ticked for the corresponding visit and 
marked as “unresolved”. In this case, a new SAE Report Form should be filled out marked as 
“Follow-up”.  
The SAE Report Form must contain the following information: 
1) Study information: 
- Protocol ID 
2) SAE information: 
- SAE name 
- Initial/Follow-up 
- Internal SAE code assigned by the Sponsor (this field is filled out by the Sponsor) 
3) Information on the investigator who reported the SAE, and information on the study site: 
- Full name of the investigator who reported the SAE 


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- Contact information (tel. and e-mail) 
- Site name and code 
- Principal Investigator's name 
4) Information on the study subject: 
Patient ID 
- Sex 
- Body weight 
- Height 
- Date of birth 
- Renal/hepatic impairment 
- Pregnancy 
- Allergies 
5) Information on the test drug: 
- INN and trade name (if this is a blind study, names are listed with “/") 
- Indication 
- Date of the first dose 
- Number of therapy cycles received (if applicable) 
- Drug batch (after which the SAE developed) 
- Dose (with which the SAE occurred) 
- Treatment start date and time (followed by the SAE) 
- Treatment stop date and time (followed by the SAE) 
- Route of administration 
- Dosage and dosing frequency 
- Is the therapy code disclosed or not (for blind studies) 
6) Information about recent (within one month) concomitant therapy or that used at the 
time of SAE onset; 
- INNs and brand names of concomitant medications 
- Indication 
- Treatment start date 
- Treatment stop date 
- Dosages, frequency, and route of administration 
- Any suspected causal relationship between the SAE and concomitant medications 
7) SAE narrative: 


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- SAE description with all symptoms and laboratory/instrumental abnormalities and 
periods indicated. 
- Time after the last dose of the investigational product  
- Autopsy data if the subject died (specifying the cause of death according to postmortem 
conclusion). If no autopsy findings are available, the cause of death should be specified 
according to the clinical conclusion. 
- Time of hospitalization (if applicable) 
8) Severity (CTCAE 4.03)  
9) Seriousness  
10) Medical history (with dates) 
11) Investigations of particular interest at onset of the SAE 
- Investigation 
- Normal limits 
- Date of the analysis 
- Result 
12) Actions taken to resolve the SAE 
- Medication / non-medication 
For medication therapy, the following should be specified: INNs and brand names of 
drugs, treatment start and stop dates, dosages, frequencies, and routes of 
administration. 
13) Actions taken regarding the investigational product  
- Discontinued/ dose reduce / unchanged 
- Dechallenge/rechallenge test results (if applicable) 
14) Outcome  
15) Signatures 
The investigator must sign (with a signature and full name) each page of the SAE Report 
Form to verify his/her responsibility for the reported information. Signed SAE Report Form is then 
submitted to the Sponsor. 
8.4. Methods and duration of follow-up of study subjects who had an AE/SAE 
If the patient discontinues the study due to an AE/SAE, the investigator will conduct further 
treatment and follow-up in accordance with the in-house standard of care for this particular 
AE/SAE. The patient should be followed up until the AE/SAE resolves completely. In case of 


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any laboratory, instrumental or vital sign abnormality, the patient should be followed up until the 
events is completely resolved (or until the value is back to the baseline level). 
See section 5.4 for further details. 
The patient withdrawn from the study due to pregnancy that occurred during the study 
should be monitored through the entire pregnancy and for 6 months after delivery to evaluate the 
mother’s and child’s health. Information on pregnancy course and outcome should be recorded in 
the source documentation. During the entire period of pregnancy, the investigator in collaboration 
with the attending Ob/Gyn specialist should monitor the patient’s overall health, the course of 
pregnancy, and laboratory values including ultrasound. When the child is born, the investigator 
together with the attending pediatrician should monitor the newborn for 6 months evaluating the 
child’s clinical status and the laboratory/instrumental findings. 
If the study subject's partner becomes pregnant, the study subject should provide the 
contacts of attending Ob/Gyn specialist to the Investigator. The investigator should monitor 
woman's health over the entire course of pregnancy. The investigator should monitor the 
pregnancy course via phone calls to attending Ob/Gyn specialist once every 3 months to assess the 
overall woman's health, pregnancy course, and laboratory/instrumental findings including the 
ultrasound. When the child is born, the investigator together with the attending pediatrician should 
monitor the newborn for 6 months evaluating the child’s clinical status and the 
laboratory/instrumental findings. 
 
 
 
 
 
 
 


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9. STATISTICS 
9.1. Description of statistical methods 
The statistical analysis will be performed using two-tailed hypothesis tests. The statistical 
significance level is 0.05. 
The Shapiro-Wilk test will be used to test the qualitative data for normality. 
The normally distributed quantitative data will be analyzed using the dependent-sample t-
test and ANOVA. The non-normally distributed data will be analyzed using the Mann-Whitney 
test and ANOVA. The regression analysis will be used for the quantitative efficacy data.  The 
categorical data will be processed using the Fisher’s exact test, Yates-corrected  𝜒2 test, and Cochran-
Mantel-Haenszel test. 
To describe the quantitative variables with normal distribution, the following parameters 
are used: means, SDs, min, max, and coefficient of variation. Non-normally distributed 
quantitative data will be described as medians and quartiles, min, max, and coefficient of variance. 
The hypothesis of BCD-085 being superior to placebo will be tested by comparing the arms 
by the 95% CIs for the primary endpoint. 
Statistical methods will be chosen based on the type and distribution of raw data. 
Appropriate statistical methods will be determined after the completion of data collection since 
data distribution and sample homogeneity cannot be assessed in advance. A list of methods may 
be expanded if necessary for conducting a high-quality study. 
 
 
 
  
 
 
 
 
 
 
 
 
 
 


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9.2. Statistical analysis steps and timelines for reports 
The final report will contain results of the 
safety, and efficacy endpoint analysis after 
the 14-week observation for 120 patients. 


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9.3. Planned number of subjects. Justification of sample size, including reasoning or 
calculations to justify statistical power and clinical justification of the study 
This study is to test the hypothesis of the test drug being superior to placebo (H0:ε ≤𝛿, 
H1:ε > δ, where ε is the true difference in the mean efficacy level between the arms, δ is the margin 
of clinically non-meaningful differences between the test arm and the placebo arm). The error 
levels were set as follows: Type 1 error of 5% (α=0.05); type 2 error of 20% (β=0.2); power of 
80%.  
The sample size required to run the study was calculated on the basis of the literature data 
on clinical efficacy of drugs inhibiting IL-17 signaling.  
The efficacy criterion used to calculate the sample size was the proportion of patients with 
moderate to severe plaque psoriasis who achieved a PASI75 at Week 12 of ixekizumab therapy in 
a clinical study that had the same design as the planned study67. The proportion of PASI75 
1. The efficacy in the test arm  (pТ) and in the placebo arm (ppl): 
2. The true difference in the frequencies between the test and the placebo arms: 
3. zα and zβ – quantiles of normal distribution N(0,1) (mean: 0, standard deviation: 1). 
 
4. k- the ratio between the sample sizes between the arms (placebo-to-test) : 
npl/nT = k. 
 
5. The superiority margin was set as follows: 
 
 
67Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, Banerjee S. Anti-
interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012 Mar 
29;366(13):1190-9. 




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After entering all data in the electronic database, an employee keeping the database checks 
it for inconsistencies, errors, and missing data points. To collect missing data or correct wrong 
data, the BIOCAD’s Medical Expert generates queries, which are study- and site-specific, i.e. 
generated for each subject individually. The Clinical Study Monitor will send queries to the study 
center by fax or e-mail. The investigator must respond within 5 working days from the date when 
the query was received. Copies of responses to queries must be kept at the study site; original 
responses must be stored at JSC BIOCAD. 
When responses to queries are received from investigators, the employee keeping the 
database checks it for inconsistencies, errors, and missing data points. When all the data from all 
the centers are collected and entered, the database is locked, and the statistical processing can be 
performed. 
Missing, not evaluable or uncertain data will not be replaced.  
Uncertain or unevaluable data will be detected during the outlier analysis by examination 
of Mahalanobis or Cook distance, visual analysis of scattering diagrams and box-plots. Data 
suspected to be outliers will be processed by the biomedical statistician together with the medical 
expert and, if necessary, the principal investigator. 
9.7. Reporting any deviations from the initial statistical plan 
If the initial study plan requires modifications, all changes will be described and explained 
in a protocol amendment or interim/final clinical study report. 
If initially defined statistical methods cannot be used, the changes should be presented in 
the final statistical report and the clinical study report. Justification of these changes should be 
given with the references to calculations, statistical parameters, and analysis of a situation that led 
to these changes. Decisions regarding emergency deviations (data-modifying allowances) can be 
made only by the Sponsor. These decisions must be explained and justified, including in the final 
study report. 
9.8. Selection of subjects for analysis 
Safety analysis 
The safety analysis will include all patients who received at least one dose of the investigational 
product. Additionally, the SAE analysis will include all randomized patients starting from the ICF 
signing and until the end of their participation in the study. 


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Efficacy analysis 
Per protocol, the efficacy analysis is to include all patients who received at least one dose 
of BCD-085/placebo and who attended at least one visit next visit. If no data are available at Week 
12, the data from the last assessment are to be used (last-observation-carried-forward method). In 
addition, these patients should be considered non-responders and analyzed separately. 
 
 
 
 
 
 
 
 
 
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The investigator/institution involved in the study must ensure direct access to source 
data/documents by the monitor, the auditor, the LEC/IRB or regulatory authorities. 
11. QUALITY CONTROL AND QUALITY ASSURANCE 
11.1. Data quality assurance 
According to ICH GCP and regulatory requirements, the Sponsor, the third party on its 
behalf, regulatory authorities, or local ethics committees can perform audits (inspections) to assure 
quality any time during the study or after its completion. The investigator is responsible for 
providing medical auditors the access to all study documentation including the source 
documentation, and for allowing his/her time and time of the study team to discuss the 
audit/inspection results and other matters with the medical auditor. 


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11.2. Protocol compliance by investigator 
Before beginning the study, the investigator must read and accept all provisions of this 
Protocol. The investigator must conduct the study in accordance with this Protocol, the ICH GCP, 
and other regulatory requirements of participating countries. 
No protocol deviations are allowed during the study without a previous written approval of 
JSC BIOCAD, the Ministry of Healthcare of the Russian Federation and Local Ethics Committees, 
except for the cases when it was necessary to protect a patient from an immediate hazard.  
The investigator should have enough time to accurately perform and complete the study 
within the time limits specified by JSC BIOCAD, enough employees of appropriate qualification, 
and adequate equipment to conduct the study according to the Protocol. 
Each sub-investigator participating in the study must read the Protocol and be aware of 
his/her responsibilities/functions in the study. If the principal investigator delegates some of 
his/her functions to sub-investigators, this must be documented in a relevant section of the 
Investigator's File. 
11.3. Investigator’s responsibility to comply with the Protocol 
At each study site, the decision regarding patient’s early withdrawal from the study has to 
be approved by JSC BIOCAD.  
If the investigator decides to withdraw a patient from the study, he/she must send a request 
(specifying a reason for withdrawal) to BIOCAD’s Medical Advisory Division by fax: 
Within 48 hours (except for weekends and public holidays) from the time when the 
request was received by the Medical Advisory Department, JSC BIOCAD should notify the 
investigator of the decision regarding patient withdrawal. If a patient has to be immediately 
withdrawn from the study due to an SAE, the investigator must inform JSC BIOCAD about the 
SAE within 24 hours but does not have to wait for approval from JSC BIOCAD.  
If a patient does not attend a scheduled visit or makes unauthorized changes in the dose of 
the investigational product, the investigator must report the violation to the Medical Advisory 
Division of JSC BIOCAD within 24 hours from the time of awareness (by fax
Medical advisors will instruct the investigator on further case management and on how to 
document the causes of the violations in the CRF/source documents.  
If the investigator fails to follow these procedures or if multiple Protocol violations occur, 
JSC BIOCAD may suspend or terminate the study at this particular study site. 


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11.4. Study monitoring 
Before the study beginning (at the Study Initiation Visit or investigators’ meeting), a 
representative (CRA) of JSC BIOCAD (or an authorized CRO) will explain the Protocol and CRF 
to the investigators and members of the study teams. During the study, the CRA will regularly visit 
the study center to check the completeness of subjects’ documentation, the accuracy of information 
in the CRF, the conformance to the Protocol and GCP, patients’ recruitment, and storage, 
dispensing, and accounting of the investigational products according to the requirements. During 
these visits, key members of the study team should be available to assist the CRA and resolve 
arising issues (if any). 
Study monitoring is performed according to appropriate SOPs of JSC BIOCAD. 
For each study subject, the investigator should keep source documents containing data 
about the subject and records made during visits (medical records of the study center), including 
demographics, medical information, laboratory findings, ECG, and all other tests or examinations. 
Any information in the CRF should be also recorded in the patient’s source documents. The 
investigator must keep the original ICF. A copy of the signed ICF will be given to the patient. 
The investigator should provide the CRA with all relevant source documents of the patient 
to confirm that data in them correspond to those in the CRF. The investigator should ensure the 
timely completeness of the CRFs before the CRA’s visit. 
The CRA will check the CRFs and other study materials comparing them against the source 
data to confirm that the study complies with the Declaration of Helsinki, the ICH GCP, regulatory 
requirements of participating countries, and the Study Protocol, and to confirm the authenticity, 
accuracy, and completeness of data. 
Upon the completion of the study, a representative of JSC BIOCAD (CRA) should visit 
the study center to perform the end-of-study visit. During this visit, the Sponsor’s representative 
will collect all necessary documentation in accordance with the SOP of JSC BIOCAD. 
11.5. Data management and quality control 
In the trials with eCRFs, JSC BIOCAD employees (or employees of an authorized CRO) 
will check the data entered by the study team members for accuracy and completeness. If there are 
any inconsistent or missing data points, queries are generated with a request for clarification. All 
queries are sent to the study site. A designated member of the study team must immediately answer 
the request and make all required changes to the database. 


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At the end of the study, any protocol deviations will be determined. After clarifying 
protocol deviations and confirming the completeness and accuracy of the data, the database is 
locked, the blind codes are opened, and the data are ready for analysis.  
11.6. Study termination 
JSC BIOCAD can suspend or terminate the study due to safety or ethical issues, Protocol 
compliance issues, or other reasons. If JSC BIOCAD suspends or terminates the study, the study 
site will be notified in advance. In case of suspension or termination, JSC BIOCAD and the 
investigator have to inform Ethics Committee and regulatory authorities in due time. If the study 
is suspended or terminated, all study information must be transferred to and all unused 
investigational product must be returned to JSC BIOCAD. 
12. ETHICS 
12.1. Ethical aspects of the study 
The study will be conducted in accordance with the ethical principles stated in the World 
Medical Association Declaration of Helsinki (Recommendations guiding physicians in biomedical 
research involving human subjects, 1964-1996) and the ICH GCP principles.  
Before the study start, the final version of the Protocol including Patient Information Sheet 
and Informed Consent Form will be submitted for approval to the Ministry of Healthcare of the 
Russian Federation, to Local Ethics Committees, and to regulatory authorities of participating 
countries. 
All subsequent protocol amendments (other than administrative amendments) must be 
approved before implementation. 
Informed consent must be obtained from patients before starting any study procedures. The 
Patient Information Sheet contains all the information that a patient may need to make a conscious 
and independent decision about whether to participate.  
During the study, all cases of SAEs will be reported to JSC BIOCAD within 24 hours. JSC 
BIOCAD will analyze the reports and may suspend the study if considered necessary. Local ethics 
committees will also be notified of all SAEs that are related, in investigator’s opinion, to the 
investigational product. 
All patient personal information is confidential and can be disclosed only if required by 
law (including court decisions).  


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All study subjects will be insured. If a patient is injured directly due to the investigational 
product, the Sponsor will cover all reasonably justified treatment expenses. 
12.2. Confidentiality of study subjects 
The investigator shall protect the confidentiality of the trial subjects, the text of this 
Protocol, and all other study materials and results.  
The investigator must ensure patient anonymity. In the CRFs and other documents 
provided by JSC BIOCAD, patients should be identified by ID codes and/or initials, but never by 
their names.  
The investigator should keep a separate log with patients' IDs, last names, addresses, phone 
numbers, and medical record numbers (if applicable). The investigator must keep data not intended 
for submission to JSC BIOCAD strictly confidential. 
No study materials proprietary to JSC BIOCAD can be transferred to a third party unless 
required by the law of the Russian Federation. 
13. DATA HANDLING AND RECORD KEEPING 
13.1. Record keeping at the study site 
All study documents must be archived at the study site or at the central archive of the 
institution. A list of all study subject identifiers should be made.  
According to the ICH GCP, essential documents include: signed protocol and amendments; 
copies of completed CRFs; signed ICFs for all patients; medical records; diaries and other source 
documents; approvals from IECs/regulatory authorities and all correspondence including approved 
documents; drug accountability records; study correspondence; and the list of patient names and 
addresses. These essential documents must be kept in the Investigator’s File. 
The investigator must retain copies of all essential documents for 5 years. 
By the end of this period, the Sponsor will inform the investigator(s) about the date when 
the documents may be destroyed. 
Study subject documentation will be archived in accordance with the site in-house SOPs. 
The investigator must inform the Sponsor about the place where essential documents are 
stored and request an approval from JSC BIOCAD before destroying any of essential documents. 
Appropriate measures must be taken to prevent the accidental or premature destruction of these 
documents. 


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13.2. Confidentiality of data 
All information about study subjects will be kept confidential. The information will be 
processed in compliance with all applicable laws and regulations. These regulations require that 
the patients be informed and give their written consent about the following questions: 
• What protected health information will be collected in this study? 
• Who will have access to this information and on what grounds? 
• Who will use or disclose this information? 
• Do study subjects have the right to recall their consent for using their confidential 
health information? 
According to the current regulations, in case the patient recalls his/her authorization to 
collect or use his/her protected health information, the investigator still can use all information 
obtained before the authorization was withdrawn. In patients who withdrew their consent for 
collection or use of confidential health data, all efforts should be made to obtain a consent at least 
for collecting information for safety follow-up (i.e. development or deterioration of existing 
adverse events) at the end of the scheduled participation in the study. 
To prevent the confidential subjects’ information from unauthorized access, the study data 
collection system has safety elements for encryption of all data to be sent in both directions. The 
access to the system will be controlled via individually assigned ID codes and user passwords 
issued only to the authorized and adequately trained personnel. They will be given only to 
authorized members of the study team who have undergone a special training. 
 
 
 
 
 
 
 
13.3. Collection of data 
This trial uses an electronic data capture (EDC) system. Designated study team members 
will enter the data required by the Protocol to eCRFs. The eCRFs have been developed with a 


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validated and safe web-based software. The study team members will get access to the EDC system 
only after being appropriately trained. An automated validation program inspects eCRFs for 
inconsistencies and allows the study team members to change or verify the entered data. 
The principal investigator is responsible for completeness and accuracy of all the data 
entered to the eCRFs and for entering and updating the information in a timely manner. 
Members of the study team will collect blood samples for the assessments of 
 
 safety of BCD-085. The samples will be then sent to the central laboratory 
for processing. 
X-ray or fluorography scans of the chest will be obtained at the study sites and interpreted 
locally. The study team member can send the scans to an appropriate institution assigned by JSC 
BIOCAD for centralized review and quality control.  
 
 
14. REIMBURSEMENT AND INSURANCE 
 
 
 
 
  
The compensation  
 
 
 
 
 
 
 
 
 
 
 
 The 
Sponsor will not reimburse the patient’s expenses for getting to the study center or other additional 
charges. The compensation is subject to taxation according to the local law. 
During the study, each study subject will be insured as a study participant according to the 
applicable law of the participating country. In the Russian Federation, patients will be insured by 


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The investigator will give a copy of the Compulsory Insurance Agreement to the patient 
and explain its terms and conditions (including the responsibilities of patients participating in the 
study). The investigator will also give the patient a certificate of compulsory insurance of the life 
and health of a drug clinical study participant. If the patient needs to make changes to the 
compulsory insurance certificate, the patient will need to return the previously issued certificate 
and receive a new one (issued within 2 working days).  
The insurance covers claims from study participants to the Insurer exclusively concerning 
reimbursement of inflicted damage to the life and health that occurred while the subject was 
participating in the clinical study. This inflicted damage is to be due to disadvantages of 
investigational products or insufficient information on them, unintended errors or neglect. Only 
claims first asserted to the Insurer within the insurance period concerning events that took place 
in the insurance territory from the beginning of the study and associated with the insured activity 
(the study) are covered. 
If the patient is injured due to the study drug or a medical procedure as per the Study 
Protocol, the patient will receive sufficient qualified medical care for free (paid by the Insurance 
company). The Insurance Company will pay for the research-related injury provided the patient 
adheres to all instructions of the investigator. 
The Insurer shall pay the following compensation amounts according to the compulsory 
Insurance Agreement (insurance payment): 
Patients in other participating countries will be insured throughout the entire study 
according to the law of the participating country. 
15. PUBLICATIONS 
After completion of the study, its results will be summarized and prepared for publication. 
The investigator must not publish any study results, including those obtained in his/her study site, 


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without a permission from JSC BIOCAD. Results from individual study sites must not be 
published before the publication of the overall study results. 








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B. I am as healthy as anybody I know 
1 
2 
3 
4 
5 
C. I expect my health to get worse 
1 
2 
3 
4 
5 
D. My health is excellent 
1 
2 
3 
4 
5 
 
 



SAP_000.pdf: 
Statistical Analysis Plan 
Protocol Number: BCD-085-2 
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STATISTICAL ANALYSIS PLAN 
Protocol Title: 
ClinicalTrials.gov Identifier: 
An International Multicenter, Randomized, Double-
blind, Placebo-controlled, Dose-finding Clinical Study of 
Efficacy and Safety of Subcutaneous BCD-085 in 
Patients with Moderate to Severe Plaque Psoriasis 
NCT02762994 
Protocol Number: 
BCD-085-2 
Protocol version  
1.1 
Version Date: 
July 12, 2016 
SAP version 
1.0 
SAP version date 
April 03, 2017 
Name and address of the 
clinical study sponsor  
JSC BIOCAD, Russia 
Legal address: 34 A, Ulitsa Svyazi, Strelna, 
Petrodvortsoviy District, Saint Petersburg, Russian 
Federation, 198515 
Postal Address: Petrovo Dalneye, Krasnogorskiy District, 
Moscow Region, Russian Federation, 143422.  
Tel.: 
 Fax: 
 
Name and function of 
person(s), authorized to sign 
the protocol and its 
amendments for the sponsor: 
Roman Alexeevich Ivanov, Vice President, Research & 
Development 
Address: Petrovo Dalneye, Krasnogorskiy District, 
Moscow Region,  
Russian Federation, 143422 
Email: 
 
Tel.:
Name, position, address and 
telephone number of the 
Medical Expert assigned by 
the Sponsor for this Study 
 
 
JSC BIOCAD, 17-A, Ulitsa Italyanskaya, 
Saint-Petersburg, Russian Federation, 198515 
E-mail: 
Tel.: 
 Fax: 
All information contained in this document is strictly confidential and intended for use by investigators, members of Ethics 
Committees and Health Authority personnel. This information cannot be disclosed to any other persons or entity, submitted 
for publication or used for any purpose other than contemplated herein without the Sponsor`s prior written authorization, 
unless it is necessary to get patient's consent for the participation in the study. 
The above requirements are effective upon the signing of this protocol. 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................................................. 3 
1. INTRODUCTION ................................................................................................................................................... 4 
2. GOALS AND OBJECTIVES ................................................................................................................................. 4 
2.1. PURPOSE ............................................................................................................................................................. 4 
2.2. OBJECTIVES ........................................................................................................................................................ 4 
2.3. HYPOTHESIS ....................................................................................................................................................... 5 
3. STUDY DESIGN ..................................................................................................................................................... 5 
3.1 DESIGN ................................................................................................................................................................ 5 
 
 
 
 
 
4. EVALUATION CRITERIA ................................................................................................................................... 7 
4.1 EFFICACY ENDPOINTS .......................................................................................................................................... 7 
4.2. SAFETY ENDPOINTS ............................................................................................................................................ 8 
 
5. THE PLANNED ANALYSIS ................................................................................................................................. 8 
6. SAMPLE SIZE CALCULATION ......................................................................................................................... 8 
7. ANALYSIS POPULATIONS ............................................................................................................................... 10 
8. ANALYSIS PLAN AND STATISTICAL METHODS ...................................................................................... 11 
8.1. THE SOFTWARE ................................................................................................................................................. 11 
8.2. DESCRIPTION OF THE STATISTICAL METHODS TO BE EMPLOYED ..................................................................... 11 
8.4. THE LEVEL OF SIGNIFICANCE TO BE USED ......................................................................................................... 15 
8.5. ACCOUNTING FOR MISSING, UNAVAILABLE OR DOUBTFUL DATA, OUTLIERS ..................................................... 15 
8.6. STATISTICAL EVALUATIONS FOR THE EARLY STUDY TERMINATION .................................................................. 15 
9. OTHER PLANNED ANALYSES ........................................................................................................................ 15 
10. DEVIATIONS FROM ANALYSIS METHODS DESCRIBED IN STUDY PROTOCOL .......................... 15 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse event 
ANOVA 
Analysis of variances 
 
 
 
 
 
 
BCD-085 
A monoclonal anti-IL17 antibody manufactured by JSC BIOCAD 
BMI 
Body mass index 
BSA 
Body surface area affected by psoriasis 
CBC 
Complete blood count 
CI 
Confidence interval 
 
 
 
 
CV 
Coefficient of variation 
DLQI 
Dermatology Quality of Life Index 
IL 
Interleukin  
JSC 
Joint Stock Company 
 
 
MAb 
Monoclonal antibody 
 
 
 
 
NAPSI 
Nail Psoriasis Severity Index  
PASI 
Psoriasis Area and Severity Index 
 
 
QoL 
Quality of Life 
SAE 
Serious adverse event 
SF-36 
Short Form Health Survey  
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
sPGA 
Static Physicians Global Assessment 
 
 
 
 
VAS 
Visual analogue scale 
 
 


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1. INTRODUCTION 
The Statistical Analysis Plan (SAP) provides a detailed analysis plan for the clinical trial 
BCD-085-2. 
2. GOALS AND OBJECTIVES 
2.1. Purpose 
To find an effective and safe dose of BCD-085 for multiple injections in patients with 
moderate to severe plaque-type psoriasis. 
2.2. Objectives 
1. To determine the number of patients in each study arm who achieved a PASI75 at Week 12 of 
treatment. 
2. To determine the number of patients in each study arm who achieved a PASI75 at weeks 4 and 
8 of treatment. 
3. To determine the number of patients in each study arm who achieve a PASI50/90 at weeks 4, 
8, and 12 of treatment. 
4. To evaluate the PASI score improvement from baseline at weeks 4, 8, and 12 in each study 
arm.  
5. To evaluate the improvement in the body surface area (BSA) affected by psoriasis from 
baseline to weeks 4, 8, and 12 in each study arm. 
6. To evaluate the improvement in the nail psoriasis severity index (NAPSI) from baseline to 
week 12 in each study arm. 
7. To determine the mean change in the intensity of pruritus measured by VAS (0-100 mm) from 
baseline to weeks1 1, 4, 8, and 12 in each study arm. 
8. To evaluate the proportion of patients in each study arm who achieved an sPGA score 0 or 1 
at weeks 4, 8, and 12 relative to baseline. 
9. To investigate patients’ quality of life in each study arm at weeks 4, 8, and 12 according to SF-
36 and DLQI.  
10. To evaluate the proportion of patients in each study arm who develop adverse events with 
multiple injections of 40 mg, 80 mg, and 120 mg BCD-085 as compared to placebo. 
 
1 The Protocol (Study goals section) had a technical misprint and mistakenly listed Week 2 as an assessment time 
point for pruritus.  No assessment was performed at Week 2.  


Statistical Analysis Plan 
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2.3. Hypothesis 
The primary hypothesis for this study is that BCD-085 is superior to placebo in patients 
with moderate to severe plaque-type psoriasis, as assessed by the proportion of patients who 
achieved a PASI 75 at Week 12. 
3. STUDY DESIGN 
3.1 Design 
This international multicenter study uses a double-blind comparative design. The purpose 
of the study is to determine a therapeutically effective dose of BCD-085 to be repeatedly 
administered in patients with moderate to severe plaque-type psoriasis, as compared with placebo. 
The study involves 120 adults with moderate to severe plaque psoriasis.  
Before inclusion in the active phase of the study, patients undergo a screening exam (max 
duration was 28 days) to determine whether they meet the inclusion/exclusion criteria. When all 
screening procedures are completed and the investigator approved patient’s inclusion in the study, 
each patient is stratified by body weight (≤80 kg / ≥81 kg), prior use of monoclonal antibodies for 
psoriasis (MAb-treated/MAb-naïve), current use of systemic non-biologics (yes/no), PASI score 
(< 20 / ≥ 20), and signs of psoriatic arthritis (yes/no). After stratification, the patients are 
randomized 1:1:1:1 to one of four study arms: 
− Arm 1: Patients receive subcutaneous injections of 40 mg BCD-085 (1.0 mL) once a week 
for the first 3 weeks (induction period) and then once every 2 weeks (maintenance period). 
For blinding purposes, these patients receive two subcutaneous injections of placebo (1.0 
mL each) together with each injection of BCD-085. Thus, the drug is administered on Day 
 
2 If neutralizing antibodies are detected in the serum samples collected for PK study 


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1 at Week 0, Day 1 at Week 1, Day 1 at Week 2 (induction period), Day 1 at Week 4, Day 
1 at Week 6, Day 1 at Week 8, and Day 1 at Week 10 (maintenance period).  
− Arm 2: Patients receive 80 mg BCD-085 (two subcutaneous injections 1.0 mL each) once 
a week for the first 3 weeks (induction period) and then once every 2 weeks (maintenance 
period). For blinding purposes, these patients receive one subcutaneous injection of 
placebo (1.0 mL) together with the injections of BCD-085. Thus, the drug is administered 
on Day 1 at Week 0, Day 1 at Week 1, Day 1 at Week 2 (induction period), Day 1 at Week 
4, Day 1 at Week 6, Day 1 at Week 8, and Day 1 at Week 10 (maintenance period). 
− Arm 3: Patients receive 120 mg BCD-085 (three subcutaneous injections 1.0 mL each) 
once a week for the first 3 weeks (induction period) and then once every 3 weeks 
(maintenance period). Thus, the drug is administered on Day 1 at Week 0, Day 1 at Week 
1, Day 1 at Week 2 (induction period), Day 1 at Week 4, Day 1 at Week 6, Day 1 at Week 
8, and Day 1 at Week 10 (maintenance period). 
− Arm 4: Patients  receive placebo as three 1.0 mL subcutaneous injections on Day 1 at 
Week 0, Day 1 at Week 1, Day 1 at Week 2, Day 1 at Week 4, Day 1 at Week 6, Day 1 at 
Week 8, and Day 1 at Week 10. 
Thus, in the active period of the study, patients are given the test drug/placebo injections 
weekly for the first three weeks of treatment and then once every 2 weeks. After assessment of the 
results at Week 12, all patients are transferred to a 4-week follow-up. During 14 weeks after the 
screening, 9 visits are performed to assess the efficacy, safety,
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4. EVALUATION CRITERIA 
4.1 Efficacy endpoints 
Primary endpoint 
− The proportion of patients in each study arm who achieved PASI 75 at Week 12 of 
treatment. 
Secondary endpoints 
− The proportion of patients in each study arm who achieved PASI 75 at weeks 4 and 8 of 
treatment. 
− The proportion of patients in each study arm who achieve PASI 50/90 at weeks 4, 8, and 12 
of treatment. 
− The PASI score improvement from baseline to weeks 4, 8, and 12 in each study arm. 
− The BSA improvement from baseline at weeks 4, 8, and 12 in each study arm. 
− The NAPSI improvement from baseline at week 12 in each study arm. 
− The mean changes in the intensity of pruritus measured by VAS (0-100 mm) in each study 
arm at weeks 1, 4, 8, and 12 relative to baseline. 
− The proportion of patients in each study arm who achieve an sPGA 0 or 1 at Weeks 4, 8, 
and 12 relative to baseline. 
− The mean change from baseline in the QoL score in each study arm (assessed using DLQI 
and SF-36 scales) at weeks 4, 8, and 12. 
 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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4.2. Safety endpoints 
− The proportion of patients who developed SAEs. 
− The proportion of patients who developed AEs. 
− The proportion of patients who developed administration site reactions. 
− The proportion of patients who developed grade 3/4 AEs/SAEs. 
− The proportion of patients who discontinued the study due to AEs/SAEs. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5. THE PLANNED ANALYSIS 
The study report will be made after the study completion (after all included patients will 
finish the study). The report  will present the efficacy analysis for 12 weeks of treatment and the 
safety 
 analyses over 14 weeks of the study. 
6. SAMPLE SIZE CALCULATION 
This study is to test the hypothesis that the test drug is superior to placebo (H0:ε ≤𝛿, 
H1:ε > δ, where ε is the true difference in the mean efficacy level between the arms, δ is the margin 
of clinically non-meaningful differences between the test arm and the placebo arm). Error levels 
are set as follows: type 1 error of 5% (α=0.05); type 2 error of 20% (β=0.2); power of 80%.  


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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The sample size required to run the study was calculated on the basis of the literature data 
on the clinical efficacy of drugs inhibiting IL-17 signaling. 
The efficacy criterion used to calculate the sample size was the proportion of patients with 
moderate to severe plaque psoriasis who achieved a PASI75 at Week 12 of ixekizumab therapy in 
a clinical study that had the same design as the planned study3. The proportion of PASI75 
responders was 76.7% in the arm treated with the lowest dose of secukinumab and 7.7% in the 
placebo arm. 
 
1. The efficacy in the test arm (pТ) and in the placebo arm (ppl): 
pТ = 
 
ppl = 
 
 
2. The true difference in the frequencies between the test and the placebo arms: 
ε = pТ–ppl = 
 
 
3. zα and zβ – quantiles of normal distribution N(0.1) (mean: 0, standard deviation: 1). 
 
4. k- the ratio between the sample sizes between the arms (placebo-to-test) : 
npl/nT = k. 
 
5. The superiority margin was set as follows: 
δ= 
 
 
With the method described by [Chow Sh.-Ch., Shao J., Wang H, 2008], the sample size 
was calculated assuming that the size of the test sample (nт) is the same as the size of the placebo 
sample (npl), i.e. k = 1. 
 
3Leonardi C, Matheson R, Zachariae C, Cameron G, Li L, Edson-Heredia E, Braun D, Banerjee S. Anti-interleukin-17 
monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012 Mar 29;366(13):1190-9. 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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𝑛T = 𝑛pl = 
(𝑧𝛼+ 𝑧𝛽)
2 ∗(𝑝𝑇∗(1 −𝑝𝑇)
𝑘
+ 𝑝𝑝𝑙∗(1 −𝑝𝑝𝑙))
(𝜀−𝛿)2
=
Thus, the study aimed at proving the efficacy of BCD-085 has to involve at least 20 patients 
(5 in each of 4 arms). However, such small samples do not allow reliably evaluating the drug safety 
and pharmacokinetics and performing appropriate inter-group comparisons. Moreover, we had to 
account for potential dropouts due to reasons not related to the study therapy. 
Taking all above said into account, the final sample size was set as 120 patients. This 
sample size allows evaluating adverse events that occur in more than 1 of 10 patients, ensures 
 
 and allows comparing the effects seen with 
different doses of BCD-085. 
 
7. ANALYSIS POPULATIONS 
Safety analysis 
The safety analysis will include all patients who received at least one dose of BCD-085. 
Efficacy analysis 
Per protocol, the efficacy analysis is planned to include all patients who received at least 
one dose of BCD-085/placebo and who attended at least one visit. If no data are available at Week 
12, the data from the last assessment should be used (last-observation-carried-forward method). In 
addition, these cases have to be considered non-responders and analyzed separately. 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
 
 
 
 
 
 
8. ANALYSIS PLAN AND STATISTICAL METHODS 
8.1. The software 
Statistical processing of the data will be performed using the Statistica 10.0 package and R 
programming language. 
8.2. Description of the Statistical Methods to be Employed 
The statistical analysis will include two-tailed hypothesis testing; the chosen significance 
level is 0.05. 
To prove the protocol-stated hypothesis of BCD-085 being superior to placebo, the 95% 
CIs will be calculated for the difference in proportions of PASI 75 achievement at Week 12 
(individual comparisons will be performed for placebo versus each BCD-085 arm). The hypothesis 
will be accepted if the lower bound of the estimated 95% CI for the difference in proportions of 
PASI 75 at Week 12 achievement is above the pre-specified margin of clinically non-meaningful 
differences (δ) of 
 
Quantitative Data 
The following quantitative data will be analyzed in the study:  
Efficacy: 
− The percent improvement from baseline in the PASI score in each study arm at 
weeks 4, 8, and 12, 
− The relative improvement from baseline in the BSA in each study arm at weeks 4, 
8, and 12, 
− The relative improvement from baseline in the NAPSI in each study arm at 
week 12, 
− The mean change from baseline in the intensity of pruritus measured by VAS (0-
100 mm) in each study arm at weeks 1, 4, 8, and 12, 
− The mean change from baseline in the QoL score in each study arm (assessed using 
DLQI and SF-36 scales) at weeks 4, 8, and 12, 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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Safety: 
− CBC results, 
− Blood chemistry results, 
− Coagulation pattern, 
− Vital signs, 
Demographics and other baseline characteristics: 
− General information (age, body weight, height, BMI), 
− Duration of the disease, severity and the area of psoriasis (PASI), BSA, severity by 
sPGA, severity of nail psoriasis (NAPSI), severity of pruritus (VAS), and the 
quality of life score (SF-26 and DLQI). 
Quantitative data will be described using the following descriptive statistics: mean, SD, 
geometric mean (for the pharmacokinetic data), median, quartiles, CV, min, and max. 
Quantitative variables will be tested for normality using the Shapiro-Wilk test. 
Normally distributed quantitative variables will be tested using the two-sample Student’s 
t-test, Welch’s t-test, and ANOVA. 
Non-normally distributed quantitative variables will be tested using the Mann-Whitney U-
test, the Wilcoxon test, the Kruskal-Wallis test, and the Friedman test. 
 
Categorical Data 
The following categorical data will be analyzed in the study: 
Efficacy: 
− The proportion of patients in each study arm who achieved PASI 50/75/90 at weeks 
4, 8 and 12 of treatment, 
− The proportion of patients in each study arm who achieve an sPGA 0 or 1 at weeks 
4, 8, and 12 relative to baseline, 
Safety: 
− The proportion of patients who developed SAEs, 
− The proportion of patients who developed AEs, 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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− The proportion of patients who developed administration site reactions, 
− The proportion of patients who developed grade 3/4 AEs/SAEs, 
− The proportion of patients who discontinued the study due to AEs/SAEs, 
 
 
 
 
  
Demographics and other baseline characteristics: 
− General information (Race, Sex, Childbearing potential (women)), 
− Prior therapies for plaque psoriasis, 
− Co-morbidities and the most relevant prior diseases.  
 
 
 
Percentages or proportions will be used to describe categorical data. 
Categorical data will be processed using frequency tables, the Fisher’s exact test, Yates-
corrected Pearson’s 𝜒2 test, and the Cochran-Mantel-Haenszel test. 
The Benjamini-Yekutieli correction for multiple testing will be used. 
 
 
 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
 
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Statistical Analysis Plan 
Protocol Number: BCD-085-2 
 
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8.4. The level of significance to be used 
The level of significance is set as 0,05 (5%) with statistical power of 0,8 (80%). 
8.5. Accounting for missing, unavailable or doubtful data, outliers 
Missing, unused, and spurious data will not be substituted. 
Spurious and unevaluable data are revealed during the outlier analysis by examination of 
Mahalanobis or Cook distance, visual analysis of scatter plots and box plots. 
All actions taken to handle missing, unevaluable, spurious data and outliers before/during 
the statistical analysis will be described in the Clinical Study Report. 
8.6. Statistical evaluations for the early study termination 
Not available. 
9. OTHER PLANNED ANALYSES 
No additional analyses are planned in this study. 
10. DEVIATIONS FROM ANALYSIS METHODS DESCRIBED IN STUDY PROTOCOL 
This Statistical Analysis Plan has no deviations from methods described in Study Protocol.