Clinical trial NCT03390101
Conditions: Moderate to Severe Plaque Psoriasis
Sponsor: Biocad
Start date: 2017-12-26; Completion date: 2022-01-20
Enrollment: 213 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
BCD-085 is an innovative drug, a monoclonal antibody against interleukin-17. The toxicity, safety, and pharmacokinetics of BCD-085 were investigated in animals, in phase I clinical study in healthy volunteers, and in phase III clinical study in patients with moderate to severe plaque psoriasis. This clinical study aims at investigating the efficacy and safety of BCD-085 every other week regimen (after induction for the first 3 weeks) versus BCD-085 one per month regimen (after induction for first 3 weeks) versus placebo in patients with moderate to severe plaque psoriasis.

Study purpose:

To investigate the efficacy and safety of BCD-085 versus placebo in patients with moderate to severe plaque psoriasis (psoriasis vulgaris)

Study objectives:

1. To compare the efficacy of BCD-085 every 2 weeks versus BCD-085 every 4 weeks versus placebo, based on the proportion of patients who achieved a PASI75, target sPGA score, and on other secondary efficacy measures.
2. To evaluate the proportion of patients in each study arm who develop adverse events with multiple injections of BCD-085 and placebo. Compare the safety profiles of BCD-085 when used every 4 weeks and when used every 2 weeks.
3. 4\. To assess the immunogenicity of BCD-085 defined as the proportion of patients who develop anti-drug antibodies (binding or neutralizing).

Detailed description:

Arms: arm 1: Patients in this arm (85 subjects) will receive 120 mg BCD-085 (two SC injections, 60 mg in 1.0 mL each). Thus, the drug will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction), Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10.

On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 1 will be given BCD-085 every 4 weeks through Week 50. arm 2: Patients in this arm (85 subjects) will receive 120 mg BCD-085 (two SC injections, 60 mg in 1.0 mL each). Thus, the drug will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction), Day 1 of Week 6 and Day 1 of Week 10. For the purpose of blind design, patients will receive a placebo (2 injections) on day 1 of week 4 and week 8.

On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 2 will continue BCD-085 every 4 weeks through Week 50. arm 3: Patients in this arm (43 subjects) will be given two SC injections of placebo (1.0 mL each) on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2, Day 1 of Week 4, Day 1 of Week 6, Day 1 of Week 8, and Day 1 of Week 10.

On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 3 will receive BCD-085 on Day 1 of Week 12, Day 1 of Week 13, Day 1 of Week 14 (induction), then every 4 weeks through Week 50.
Interventions: intervention 1: BCD-085 Q2W intervention 2: BCD-085 Q4W intervention 3: Placebo
Intervention descriptions: intervention 1: In Arm 1, the test drug BCD-085 will be used at a dose of 120 mg given as two SC injections according to the following schedule: once a week for the first 3 weeks (induction treatment) and then once every 2 weeks through Week 10.

On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label patients will receive BCD-085 through week 50. The follow-up will continue through week 54. intervention 2: In Arm 2, and then once every 4 weeks through Week 10. On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 2 will be given BCD-085 once every 4 weeks through week 50. The follow-up will continue through week 54. intervention 3: In Arm 3, patients will be given two SC injections of placebo (1.0 mL each) according to the following schedule: on Day 1 of weeks 0, 1, 2 and then once every 2 weeks through Week 10.

On Week 12, the treatment efficacy will be assessed with a PASI75 score, and the therapies will be unblinded. During the open-label period, patients from Arm 3 will receive BCD-085 at weeks 12, 13, 14 and then once every 4 weeks through week 50. The follow-up will continue through week 54.

Protocol documents:
Prot_000.pdf: 


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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ................................................................................................................ 2 
SIGNATURE SHEET ..................................................................................................................... 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 
SYNOPSIS .................................................................................................................................... 21 
1. STUDY JUSTIFICATION ........................................................................................................ 40 
1.1. Introduction ......................................................................................................................... 40 
1.1.1. 
Overview of disease pathogenesis, epidemiology, and currently available 
treatment options ............................................................................................................... 40 
1.1.2. 
Background information for studied therapy ....................................................... 42 
1.2. Name and description of the investigational products ........................................................ 44 
1.2.1. Test drug .................................................................................................................. 44 
1.2.2. Placebo ..................................................................................................................... 45 
1.2.3. Labeling of the investigational products .................................................................. 45 
1.3. Relevant non-clinical and clinical aspects .......................................................................... 47 
1.3.1. Non-clinical studies ................................................................................................. 47 
1.3.2. Clinical studies ......................................................................................................... 64 
1.3.3. Conclusions and study rationale .............................................................................. 89 
1.4. Summary of the known and potential risks and benefits, if any, to human subjects 
(risk/benefit balance) ................................................................................................................. 91 
1.4.1. Benefit assessment ................................................................................................... 91 
1.4.2. Risk assessment ....................................................................................................... 91 
1.4.3. Conclusions .............................................................................................................. 93 
1.5. Description of and justification for the route of administration, dosage, dosing regimen, 
and treatment period .................................................................................................................. 94 
1.5.1 Description and justification of the study design ..................................................... 94 
1.5.2. Description of and justification for the route of administration, dosage, dosing 
regimen, and treatment period ........................................................................................... 96 
1.5.3. Justification of placebo use ...................................................................................... 98 
1.6. Clinical study compliance with regulatory requirements ................................................... 98 
1.7. Description of study population .......................................................................................... 99 
1.8. References ........................................................................................................................... 99 


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2. STUDY AIMS AND OBJECTIVES ....................................................................................... 103 
2.1 Study aims .......................................................................................................................... 103 
2.2 Study objectives ................................................................................................................. 103 
3. STUDY HYPOTHESIS .......................................................................................................... 103 
4. STUDY DESIGN .................................................................................................................... 104 
4.1. Primary and secondary outcome measures to be assessed in the study ............................ 104 
4.1.1. Primary endpoint ................................................................................................... 104 
4.1.2 Secondary endpoints ............................................................................................... 104 
4.2. Description of the study type/design, study flow-chart, study procedures and periods ... 106 
4.3. Measures to minimize/eliminate bias................................................................................ 114 
4.3.1. Distribution of patients by study sites ................................................................... 114 
4.3.2. Procedure of assigning study IDs .......................................................................... 114 
4.3.3. Stratification procedure ......................................................................................... 115 
4.3.4. Randomization procedure ...................................................................................... 119 
4.3.5. Blinding and subject-specific lots of investigational products .............................. 123 
4.4. Description of the study treatment, doses, and dosing regimen of the investigational 
products. Description of the dosage form, packaging, and labeling of the investigational products
 ................................................................................................................................................. 123 
4.4.1. Description of the study treatment, doses, and dosing regimen of the investigational 
products ........................................................................................................................... 123 
4.4.2. Description of the dosage form, packaging, and labeling of the investigational 
products ........................................................................................................................... 125 
4.5. Expected duration of the study and subjects’ participation in the study .......................... 125 
4.6. Description of the sequence and duration of all study periods ......................................... 125 
4.6.1 Study visits and procedures .................................................................................... 125 
Information for the Investigator about allowed changes in scheduled dates of visits ..... 145 
4.6.2. Procedures by visits ............................................................................................... 147 
4.7. Description of individual study procedures ...................................................................... 171 
4.7.1. History taking, complaints, demographics ............................................................ 184 
4.7.2. Physical examination ............................................................................................. 185 
4.7.3. Vital signs .............................................................................................................. 185 
4.7.4. Laboratory tests ..................................................................................................... 186 
4.7.5. ECG ....................................................................................................................... 190 
4.7.6. Tuberculosis diagnostics ........................................................................................ 190 
4.7.7. Chest x-ray ............................................................................................................. 193 
4.7.8. Assessment of the severity and area of psoriasis (PASI), including body surface 
area affected by psoriasis (BSA) ..................................................................................... 194 
4.7.9. Static Physician’s Global Assessment (sPGA) ...................................................... 198 


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4.7.10. Quality of life assessment .................................................................................... 200 
4.7.11. Nail Psoriasis Severity Index (NAPSI) ................................................................ 201 
4.7.12. Patient assessment of itch .................................................................................... 203 
4.7.13. Assessment of psoriatic arthritis .......................................................................... 203 
4.7.14. Diagnostics of depression .................................................................................... 206 
4.7.15. Blood drawing for immunogenicity testing ......................................................... 210 
4.7.16. Storage and shipping of biospecimens ................................................................ 212 
4.7.17. Total blood volume taken during the study ......................................................... 213 
 
4.7.19. Assessment of the Patient’s Diary ....................................................................... 219 
4.7.20. Data entering to eCRF ......................................................................................... 219 
4.8. Stop rules and criteria for premature withdrawal for study subjects, study periods, and 
study as a whole ....................................................................................................................... 219 
4.8.1. Stop rules for study as a whole .............................................................................. 219 
4.8.2. Criteria for premature withdrawal of study subjects ............................................. 220 
4.9. Drug accountability ........................................................................................................... 221 
4.9.1. Handling of the investigational products ............................................................... 222 
4.10. Procedure for code keeping and unblinding ................................................................... 222 
4.11. Data entered directly into CRF (i.e. no prior written or electronic record of data) and 
considered as source data ......................................................................................................... 223 
5. ELIGIBILITY AND EXCLUSION OF STUDY SUBJECTS ................................................ 223 
5.1. Inclusion criteria ............................................................................................................... 224 
5.2. Exclusion criteria .............................................................................................................. 224 
5.3. Withdrawal criteria ........................................................................................................... 228 
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 ...................................................................... 229 
5.4.1. Follow-up of patients who received at least one dose of the investigational product . 
 
 ........................................................................................................................... 229 
5.4.2. Follow-up of subjects who did not receive a single dose of the investigational 
product  ........................................................................................................................... 230 
6. TREATMENT OF STUDY SUBJECTS ................................................................................ 231 
6.1. Study therapy .................................................................................................................... 231 
6.1.1. Preparation of the investigational products for administration and administration 
procedure ......................................................................................................................... 232 
6.1.2. Adjustment and discontinuation of study therapy ................................................. 234 
6.1.3. Overdose ................................................................................................................ 235 
6.2. Concomitant therapy, medications allowed and prohibited by the Protocol .................... 235 
6.2.1. Allowed concomitant therapy ................................................................................ 235 


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6.2.2. Prohibited concomitant therapy ............................................................................. 235 
6.3. Compliance with study procedures ................................................................................... 236 
6.3.1. Treatment compliance ........................................................................................... 236 
7. ASSESSMENT OF EFFICACY ............................................................................................. 238 
7.1 List of efficacy variables .................................................................................................... 238 
7.1.1. Definition of variables ........................................................................................... 238 
7.1.2. Efficacy endpoints ................................................................................................. 238 
7.1.2.1. Primary endpoint ................................................................................................ 238 
7.1.2.2. Secondary endpoints in the main treatment period (Week 0 to Week 54): ........ 238 
7.1.2.3. Efficacy endpoints during the extension study period (Week 54 through Week 
166) 
 ........................................................................................................................... 239 
7.2 Methods and timeframes for assessment, documenting, and analysis of efficacy variables
 ................................................................................................................................................. 240 
7.2.1 Timeframes for analysis of efficacy variables ........................................................ 240 
7.2.2 Methods and timeframes for assessment and documenting of efficacy variables .. 240 
8.1. List of safety variables ...................................................................................................... 241 
8.1.1. Terms and definitions ............................................................................................ 241 
8.1.2. Safety endpoints ..................................................................................................... 243 
8.2. Methods and timeframes for assessment, documenting and analysis of safety variables 243 
8.2.1. Timeframes for analysis of safety variables .......................................................... 243 
8.2.2. Methods and timeframes for assessment and documenting of safety variables .... 244 
8.3 Requirements for reports, procedures for registration and reporting AEs, and filling out AE 
Report Forms ........................................................................................................................... 245 
8.3.1. Recording AEs/SAEs ............................................................................................. 245 
8.3.2. AE/SAE reporting .................................................................................................. 247 
8.3.3. Reporting cases of study subject’s pregnancy/study subject’s partner’s pregnancy ... 
 
 ........................................................................................................................... 250 
8.3.4. Recording administration errors with the investigational product ........................ 250 
8.3.5. Reporting drug overdose ........................................................................................ 251 
8.4. Methods and duration of follow-up for study subjects after the onset of AE/SAE .......... 251 
8.5. Immunogenicity study ...................................................................................................... 252 
9. STATISTICS ........................................................................................................................... 253 
9.1. Description of statistical methods ..................................................................................... 253 
9.2. Statistical analysis steps and timelines for reports ............................................................ 255 
9.3. Planned number of subjects. Justification of sample size, including reasoning or 
calculations to justify statistical power, and clinical justification of the study ....................... 255 
9.3.1. Non-inferiority hypothesis ..................................................................................... 255 
9.3.2. Superiority hypothesis ........................................................................................... 257 


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9.4. Suitable significance level ................................................................................................ 258 
9.5. Statistical criteria for stopping and/or terminating the study ............................................ 258 
9.6. Handling of missing, unevaluable or uncertain data ......................................................... 259 
9.7. Reporting any deviations from the initial statistical plan ................................................. 259 
9.8. Selection of subjects for analysis ...................................................................................... 260 
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ................................................... 260 
11. QUALITY CONTROL AND QUALITY ASSURANCE .................................................... 260 
11.1. Data quality assurance .................................................................................................... 260 
11.2. Investigator’s adherence to the Protocol ......................................................................... 261 
11.3. Investigator’s responsibility to comply with the Protocol .............................................. 261 
11.4. Study monitoring ............................................................................................................ 262 
11.5. Data management and quality control ............................................................................ 262 
11.6. Study termination ............................................................................................................ 262 
12. ETHICS ................................................................................................................................. 263 
12.1. Ethical aspects of the study ............................................................................................. 263 
12.2. Confidentiality of study subjects .................................................................................... 264 
13. DATA HANDLING AND RECORD KEEPING ................................................................. 264 
13.1. Record keeping at the study site ..................................................................................... 264 
13.2. Confidentiality of data .................................................................................................... 265 
13.3. Collection of data ............................................................................................................ 266 
14. REIMBURSEMENT AND INSURANCE ........................................................................... 266 
15. PUBLICATIONS .................................................................................................................. 267 
16. ANNEXES ............................................................................................................................ 268 
Annex 1. Injection Site Reaction Form.................................................................................... 268 
Annex 2. VAS for assessing itch severity (template) .............................................................. 269 
Annex 3. VAS for assessing psoriatic arthritis (templates) ..................................................... 270 
Annex 4. HAQ-DI questionnaire to assess functional activity ................................................ 272 
 


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SIGNATURE SHEET 
To Protocol version 2.0 of November 02, 2018: “An International, Multicenter, Randomized, Double-blind, Placebo-
Controlled Clinical Study to Compare the Efficacy and Safety of Two Dosing Regimens of BCD-085 (JSC BIOCAD, 
Russia) 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 study as 
outlined in this Protocol, the ICH GCP, and applicable regulations 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 
 
______________________________ 
Signature 
______________________________   
Date 


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ABBREVIATIONS 
AUC 
Area under the concentration vs. time curve 
AE 
Adverse event 
ALT 
Alanine transaminase  
AnSc 
Anaphylaxis score 
AP 
Alkaline phosphatase 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate transaminase 
AUMC 
Area under the first moment curve 
BAbs 
Binding antibodies 
BCD-085 
Monoclonal anti-IL17 antibody manufactured by JSC BIOCAD 
BP 
Blood pressure 
BSA 
Body surface area affected 
CHF 
Congestive heart failure 
Cl 
Total clearance 
Cmax 
Maximum drug concentration in the plasma 
Cmin 
Minimum concentration 
CNS 
Central nervous system 
CRF 
Case Report Form 
CTCAE 
Common Toxicity Criteria for Adverse Events 
DLQI 
Dermatology Quality of Life Index  
DNA 
Deoxyribonucleic acid 
ESR 
Erythrocyte sedimentation rate 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
HBcor 
Hepatitis B core antigen 
HBsAg 
Hepatitis B surface antigen 


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HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HDL 
High-density lipoproteins 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
ICH 
International Conference on Harmonization 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IL 
Interleukin  
INN 
International non-proprietary name 
ITT 
Intention-to-treat population (all patients who were randomized in the study, 
whether they completed the study per protocol or discontinued it due to any 
reason) 
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  
NSAIDs 
Non-steroidal anti-inflammatory drugs 
NYHA 
New York Heart Association 
PASI 
Psoriasis Area and Severity Index 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PP 
Per-protocol population (all patients who completed the study per protocol) 
Q2W 
Once every 2 weeks 
Q4W 
Once every 4 weeks 
RNA 
Ribonucleic acid 


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SAE 
Serious adverse event 
SOP 
Standard Operating Procedure 
sPGA 
Static Physician’s Global Assessment 
SS 
Separate subdivision 
t½ 
Elimination half-life 
TC 
Total cholesterol 
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 2-3% of the population 
have 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 treatment-resistant forms of psoriasis have become more 
common, which significantly affects the patients’ quality of life and leads, in some cases, to 
disability (about 1% of patients with psoriasis). This determines the social significance of 
psoriasis. According to Krueger et al., psoriasis, as a medical and social problem and a factor 
reducing quality of life, shares the first place with depression, cardiovascular disorders, and 
diabetes. 
Today, psoriasis is considered incurable. However, advanced treatment options are able to 
significantly improve the clinical course of the disease. 
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 to patients with mild 
psoriasis. 
Phototherapy is an important option in the treatment of psoriasis. It includes 
photochemotherapy (PUVA), a combination of the UVA light and a photosensitizing agent taken 
orally; selective phototherapy, a combination of middle-wave and long-wave UV light; and 
narrow-band UVB therapy. The light is likely to exert its therapeutic effects by stimulating 


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production of cytokines with immunosuppressive effects, by enhancing expression of several 
molecules on the cell surface, and by inducing cell apoptosis. 
Retinoids (synthetic vitamin A derivatives) have been used in psoriasis for more than 25 
years. Retinoids 
inhibit 
proliferation of 
epidermis, normalize keratinization, exert 
immunomodulating effects on dermal cells, and stabilize membrane structures of cells. 
In recent decades, opinions about mechanisms of psoriasis have changed, and now psoriasis 
is understood to be a systemic autoimmune disease. Thus, approaches to its therapy have been 
revised. Cytostatics (methotrexate), systemic glucocorticoids, and cyclosporine for the treatment 
of moderate to severe psoriasis are taking a backseat to more selective agents. 
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 minimal adverse 
effects. 
Biologics used in clinical practice can be classified as follows [1]: 
• Inhibitors of tumor necrosis factor-alpha (adalimumab, certolizumab, etanercept, 
golimumab, and infliximab), 
• Inhibitors of the similar p40 subunit of the proteins IL-12 and IL-23 (ustekinumab), 
• Inhibitors of interleukin-17 or its receptor (secukinumab, ixekizumab, brodalumab). 
The first biologics approved by the FDA for the treatment of psoriasis (2003) 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 long-term use of the drug [1]. 
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 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]. 


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The recent findings suggest that interleukin-17 plays a key role in the development of 
psoriasis. Several drugs blocking this cytokine demonstrated high efficacy and favorable safety in 
a number of pivotal clinical studies [15-24]. The known interleukin-17-blocking drugs differ in 
the type of antibody used, the structure of the Fc fragment, and physicochemical properties. 
Secukinumab, for example, is a fully human antibody (Ig G1) that selectively binds to and 
neutralizes interleukin 17A (IL-17A). The FDA (U.S. Food and Drug Administration) and EMA 
(European Medicines Agency) approved secukinumab on the basis of four Phase 3 studies, 
including those in adults with moderate to severe plaque psoriasis diagnosed at least 6 months 
before the study initiation. All the studies were multicenter, placebo-controlled, and double-blind. 
They involved a total of 2403 patients. Most of the study subjects (> 50%) had clear or almost 
clear skin after 12 weeks of treatment with 300 mg secukinumab, which refers to at least 90% 
improvement of all symptoms as compared to baseline (PASI 90) [21-23]. In a more recent 
study (CLEAR; 679 patients), in which secukinumab was compared with ustekinumab, 44% of 
patients on secukinumab and 28% of patients on ustekinumab achieved PASI 100 at Week 16 of 
treatment [24]. 
Psoriasis is a common and socially significant chronic disease. Thus, development of drugs 
that block IL-17 signaling is a promising approach in searching for new highly effective and safe 
treatments for psoriasis. 
1.1.2. Background information for studied therapy 
Although the exact mechanism of psoriasis is unknown, the pathological process is thought 
to involve both innate and adaptive immune responses affecting keratinocytes and other skin cells 
such as fibroblasts, mast cells, and endothelial cells [2, 3, 4]. 
A psoriatic plaque becomes infiltrated with activated T-cells that produce a number of 
cytokines, i.e. interferon-gamma, tumor necrosis factor-alpha, interleukin-17 (17A), and 
interleukin-22 [2, 5, 6, 7]. Certain substances are produced by the dendritic cells (interleukin-23, 
interleukin-20, and TNF-α) and keratinocytes (CXCL8, CXCL1, CCL20) [3, 8, 9]. After the role 
of the cytokines in psoriasis has been demonstrated, a large number of studies have been initiated 
to investigate effects of blocking particular molecules. Results obtained in these studies suggest 
that interleukin-17 (produced by the T-cells in response to interleukin-23) plays a key role in skin 
damage [10].  


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Interleukin-17 exhibits significant pro-inflammatory activity in vitro and in vivo, can 
induce the synthesis of various inflammatory mediators (including TNF-α and interleukins 1, 6 
and 8 (CXCL8) [29, 30, 31], and stimulates keratinocytes to produce various chemokines [26, 27, 
28], thus promoting inflammation in psoriasis patients. 
IL-17 blockade reduces the production of pro-inflammatory cytokines, secretion of 
chemokines by keratinocytes, and, therefore, suppresses the inflammation. The clinical effect is 
the reduction of the pathological processes in the psoriatic plaque and limiting the area of the 
affected skin. Thus, blockade of this cytokine in patients with psoriasis is thought to be a promising 
and justified therapeutic approach. 
It is interesting that available effective treatments affect either IL-23 or IL-23-induced IL-
17. Ustekinumab suppresses IL-23 and IL-12 (yet several small studies have shown that IL-12 
inhibition has a little impact on the overall efficacy of ustekinumab) [10]. The clinical efficacy of 
other psoriasis treatments (cyclosporine, phototherapy, etanercept, TNF inhibitors) positively 
correlates with the suppression of interleukin-17 [11, 12, 13, 14]. These data confirm the essential 
role that interleukin-17 plays in the pathogenesis of psoriasis and justify the feasibility of 
developing clinically effective drugs affecting this signal pathway. 
In 2012, the data were published illustrating the clinical effect of monoclonal antibodies 
specifically interacting with IL-17 (or IL-17 receptor) in patients with moderate to severe psoriasis. 
In clinical studies, the proportion of PASI 75 responders after 12 weeks of treatment was up to 
89.7% in the test drug arms and up to 9% in the placebo arm [15-24]. Moreover, the new drugs 
were shown superior to such approved and effective medications as etanercept and ustekinumab 
[16, 18, 24]. 
JSC BIOCAD has developed an original anti-IL-17 monoclonal antibody (BCD-085) that 
has several advantages. 
 
 As of now, a full range 
of non-clinical investigations and phase I and II clinical studies has been conducted with BCD-
085. In the non-clinical program, the drug showed in vitro and in vivo potency, low 
immunogenicity, and low toxicity, and was well tolerated by the animals. In the Phase I dose-
escalation clinical study when single doses of BCD-085 were given subcutaneously to healthy 
volunteers, the pharmacokinetics of the drug was characterized, and its suitable tolerability and 
safety were demonstrated. Phase II clinical studies in patients with moderate to severe plaque 


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psoriasis and patients with active ankylosing spondylitis showed significant superiority of BCD-
085 over placebo and its favorable safety profile. 
Thus, the evidence available shows an apparent potential of developing BCD-085, which 
should result in a new highly-effective and safe treatment for psoriasis. 
1.2. Name and description of the investigational products 
Investigational products in this study include BCD-085 (test drug) and placebo. 
1.2.1. Test drug 
Trade name: not assigned. 
Internal code: BCD-085. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1.2.2. Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.2.3. Labeling of the investigational products 
Labeling during the blinded treatment period 
The treatment will be blinded until Week 12, so both investigational products will be 
labeled the same way during this period. 
According to Article 46 of Federal Law 61-FZ “On the Circulation of Medicines” of April 
12, 2010 and regulatory requirements of the Republic of Belarus, the primary packaging of the 
investigational product will contain the following information (printed in Russian, in the easily 
readable font): 
- BCD-085/placebo, 
- Lot No, 
- Date of manufacture, 
- Shelf life, 
- Dosage. 


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The secondary packaging will contain the following information (printed in Russian, in the 
easily readable font): 
- BCD-085/placebo, 
- Manufacturer’s name: JSC BIOCAD, Russia,  
- Lot No, 
- Date of manufacture, 
- Shelf life, 
- Route of administration, 
- Dosage, 
- Pharmaceutical form, 
- Prescription status, 
- Storage conditions, 
- Cautionary labeling, 
- Visit name. 
Both the primary and secondary packaging will also have the “For clinical studies only” 
label. 
The secondary packaging also will contain the following information: protocol code, 
patient’s identification number, date of injection.  
Labeling during the open-label treatment period 
The period from Week 12 to Week 158 (for Arms 1 and 2) or from Week 12 to Week 174 
(for Arm 3) is open-label, so no treatment blinding is required. 
According to Article 46 of Federal Law 61-FZ “On the Circulation of Medicines” of April 
12, 2010 and regulatory requirements of the Republic of Belarus, the primary packaging of the 
investigational product will contain the following information (printed in Russian, in the easily 
readable font): 
- Name of the investigational product (BCD-085), 
- Batch, 
- Date of manufacture, 
- Shelf life, 
- Dosage. 


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The secondary packaging will contain the following information (printed in Russian, in the 
easily readable font): 
- Name of the investigational product (BCD-085), 
- Manufacturer’s name: JSC BIOCAD, Russia, 
- Batch, 
- Date of manufacture, 
- Shelf life, 
- Route of administration, 
- Dosage, 
- Pharmaceutical form, 
- Prescription status, 
- Storage conditions, 
- Cautionary labeling. 
Both the primary and secondary packaging will also have the “For clinical studies only” 
label. 
The secondary packaging also will contain the following information: protocol code, 
patient’s identification number, date of injection.  
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 antibody selectively targeted the human IL-17A antigen and had a high 
binding constant
 
 
 
 
 
 
 
 


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1.3.1.2. Non-clinical pharmacodynamics 
 
 
 
 
 
  
 
 
 
 
 
 










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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 
involved joint surface was lower than that in the controls at all time points. The most pronounced 
effect was observed in animals treated with the lowest dose (4.0 mg/kg). The percentage of 
involved joint surface was significantly lower than that in the controls starting from Week 4 of the 
experiment (counted starting from the first injection) and until the end of the experiment. For 
animals dosed with 8.0 mg/kg BCD-085, significant differences were seen only at the end of the 
experiment. 
Examination of the metacarpophalangeal and metatarsophalangeal joints showed the 
changes typical for the initial signs of arthritis in the placebo-dosed animals. Disappearance of the 
lamina splendens was observed in all animals. The surface zone opened directly in the joint cavity 
as a homogeneous matrix. Selective staining with toluidine blue revealed swelling and slight in 
the surface zone, and metachromasia on the surface detecting focal disappearance of acidic 
glycans. Signs of apoptosis, hypertrophy, and proliferation were seen in the chondrocytes. The 
synovial membrane was moderately swollen and plethoric with insignificant signs of proliferation. 
No lymphoplasmacytic proliferation was observed. The subchondral plate and underlying bone 
trabeculae were normal. 
Disappearance of the lamina splendens was observed in one animal (No. 3) from the 4.0 
mg/kg group. In other cases, the cartilage remained intact, and the synovial membranes had no 
signs of damage or inflammation. No proliferation of synoviocytes was observed. 
Animals from the 8.0 mg/kg group had intact cartilages; no disruption of the surface pattern 
was seen, and the ratio between the matrix and cellular structure was normal. The matrix and 
associated chondrocytes were organized in three appropriately oriented, well-ordered zones 
(superficial, central, and deep). The subchondral plate and underlying bone trabeculae were 
normal. The synovial membrane was normal with no signs of proliferation. 
Repeated (once a week for 4 weeks) SC administration of BCD-085 to cynomolgus 
monkeys (Macaca fascicularis) was associated with a significant reduction of inflammation and 
degeneration induced by two injections of collagen. These results were supported by the 
histological findings as well. 


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1.3.1.2.3. Repeated-dose pharmacokinetics study of BCD-085 
Pharmacokinetics of BCD-085 was studied in healthy cynomolgus monkeys (Macaca 
fascicularis) after multiple SC injections at doses of 2 mg/kg, 8 mg/kg, and 40 mg/kg (18 animals).  
The repeated-dose PK parameters were investigated with 2.0 mg/kg, 8.0 mg/kg, and 40.0 
mg/kg doses. The highest dose used in this study (40 mg/kg) equaled 10 doses that showed the 
maximum anti-inflammatory effect in the PD study performed in collagen-induced arthritis (CIA) 
model. This meets requirements stated in both Russian and international regulations15. 
The animals were divided into three groups according to drug doses assigned. 
BCD-085 was administered subcutaneously in the withers once a week for 25 weeks. This 
administration mode corresponds to one recommended for clinical use. The following doses were 
used in the study: 2 mg/kg, 8 mg/kg, and 40 mg/kg. The injection volume was 0.8 mL/kg. BCD-
085 was administered at a dose of 2.5 mg/mL in the minimum-dose group, 10.0 mg/mL in the 
medium-dose group, and 50.0 mg/mL in the maximum-dose group. 
Serum levels of BCD-085 were evaluated by means of ELISA. Experimental data were 
used to calculate the AUC0-168 (an integral index characterizing the changes in the drug 
concentration after the first injection during the dosing period of 168 h) and AUCss168 (4032-4200) 
(steady-state AUC referring to the 168-h dosing interval). In addition, the accumulation ratio was 
calculated as the ratio of AUCss168 (4032-4200) to AUC0-168. The values of AUC0-168 and AUCss168 (4032-
4200) were dose-proportional, while the values of half-life period did not depend on the dose of 
BCD-085. This suggested the linear pharmacokinetics of BCD-085. 
The accumulation ratio did not depend on the dose and was similar across the groups. The 
accumulation ratio was 2.35 with BCD-085 2.0 mg/kg, 2.68 with BCD-085 8.0 mg/kg, and 2.17 
with BCD-085 40.0 mg/kg. 
                                                          
15 Guidelines for non-clinical studies of medicinal products (edited by A.N. Mironova, M. Federal State Budgetary 
Institution Scientific Center for Expert Evaluation of Medical Products of the Ministry of Healthcare of the Russian 
Federation, 2012, in two volumes); Guideline on experimental (non-clinical) investigation of new pharmacological 
compounds // M. - 2005; Guidelines on evaluation of medicinal products (edited by Mironova A.N., M. Federal State 
Budgetary Institution Scientific Center for Expert Evaluation of Medical Products, 2014, in two volumes); Guidelines 
on the quality, safety, and efficacy of biotherapeutic protein products prepared by recombinant DNA technology. 
World Health Organization – 2013; ICH Harmonised Tripartite Guideline Preclinical Safety Evaluation of 
Biotechnology-Derived Pharmaceuticals S6(R1) – 2011 
 
 


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The PK parameters were calculated based on the concentrations of BCD-085 in the serum 
of all experimental animals. 
1.3.1.2.4. Single-dose toxicity of BCD-085 
The following doses of BCD-085 were used in a single-dose SC toxicity study: 8.0 mg/kg, 
40.0 mg/kg, and 80.0 mg/kg. The minimum dose used in this study is equivalent to the expected 
therapeutic dose in humans with the 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 involved 16 male and female monkeys (Macaca fascicularis) with body weight 
from 3.0 kg to 7.0 kg: 
1. BCD-085 8 mg/kg (2 males and 2 females) 
2. BCD-085 40 mg/kg (2 males and 2 females); 
3. BCD-085 80 mg/kg (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; 
• Changes in vegetative reactions (pupil diameter, eye slit size, salivation, involuntary 
defecation, urination, increased diuresis); 
• Changes in pelage (piloerection, alopecia, pelage color); 
• Eye changes (tearing, discharge); 
• Effects on animal behavior. 
The study results showed that BCD-085 in the tested doses did 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 limited volume that could be injected). The general health of animals was 
satisfactory throughout the entire experiment; no body weight loss was registered. CBC parameters 
and blood chemistry markers of the liver and urinary system did not change during the observation 
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Some decrease in the serum glucose level was observed with the medium (40 mg/kg) and 
high (80 mg/kg) 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 BCD-085 40.0 mg/kg and 80.0 mg/kg 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 30 monkeys (Macaca fascicularis). BCD-085 
was administered subcutaneously in the withers once a week for 25 weeks. This administration 
mode corresponds to one recommended for clinical use. The following doses were used in the 
study: 2 mg/kg, 8 mg/kg, and 40 mg/kg. The injection volume was 0.8 mL/kg. BCD-085 was 
administered at a dose of 2.5 mg/mL in the minimum dose group, 10.0 mg/mL in the medium-
dose group, and 50.0 mg/mL in the maximum dose group. The highest dose used in this study (40 
mg/kg) equaled 10 doses that showed the maximum anti-inflammatory effect in the PD study 
performed in collagen-induced arthritis (CIA) model. This meets requirements stated in both 
Russian and international regulations16. The maximum concentration of BCD-085 used in this 
study was higher than the concentration planned to be used in clinical studies.  
The recovery period (drug-free) was 8 weeks. The animals were divided into 5 groups 
according to the doses of the test drug and the time when they were euthanized: the minimum dose 
group (2 mg/kg, 1 male and 1 female euthanized at the end of the recovery period), the 
medium-dose group (8 mg/kg, 1 male and 1 female euthanized at the end of the recovery period), 
the maximum dose/main group (40 mg/kg, 3 males and 3 females euthanized after 25 doses of 
BCD-085), the maximum dose/satellite group (40 mg/kg, 3 males and 3 females euthanized at the 
end of the recovery period), and the placebo control group (3 males and 3 females euthanized at 
the end of the recovery period).  
                                                          
16 Guidelines for non-clinical studies of medicinal products (edited by A.N. Mironova, M. Federal State Budgetary 
Institution Scientific Center for Expert Evaluation of Medical Products of the Ministry of Healthcare of the Russian 
Federation, 2012, in two volumes); Guideline on experimental (non-clinical) investigation of new pharmacological 
compounds // M. - 2005; Guidelines on evaluation of medicinal products (edited by A.N. Mironova, M. Federal State 
Budgetary Institution Scientific Center for Expert Evaluation of Medical Products, 2014, in two volumes); Guidelines 
on the quality, safety, and efficacy of biotherapeutic protein products prepared by recombinant DNA technology. 
World Health Organization – 2013; ICH Harmonised Tripartite Guideline Preclinical Safety Evaluation of 
Biotechnology-Derived Pharmaceuticals S6(R1) – 2011. 


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The toxicological profile of the study drug was assessed by using common experimental 
methods recommended for non-clinical studies. 
The following parameters were monitored during the study: motor activity, vegetative 
reactions, pelage, eye changes, nasal mucosa, oral mucosa, stool, appetite, breathing pattern, 
urinary function, and cellular profile of peripheral blood. Also, the effects of BCD-085 on the 
following were assessed: 1) blood clotting system; 2) protein, carbohydrate metabolic and 
enzymatic functions of the liver (by means of blood chemistry – liver function tests, total bilirubin, 
cholesterol, protein, triglycerides, and glucose), 3) urinary system (urinalysis and blood chemistry: 
urea, creatinine, sodium, and potassium); 4) cardiovascular system (ECG); and 5) central nervous 
system. 
The animals were euthanized according to the standard protocol for the postmortem 
examination of the viscera. 
The animals tolerated well the anti-IL-17 monoclonal antibody. No body weight loss, 
behavioral changes or thermogenic reactions were registered in any experimental animal over the 
entire study. Multiple injections of BCD-085 (2 mg/kg, 8 mg/kg, or 40 mg/kg) did not change 
major CBC or clotting parameters, did not affect the functions of the liver, urinary or 
cardiovascular systems. 
No changes in autonomic reactions (pupil diameter, eye slit size, salivation, involuntary 
defecation, urination, increased diuresis) were observed. The test drug did not affect pelage 
(caused no piloerection, alopecia, or changes in pelage color), did not lead to any eye changes 
(tearing, discharge), did not affect nasal or oral mucosa. Throughout the entire study, no drug 
effects on animal appetite were observed (food or water consumption). Neither did repeated 
administration of the drug affect the stool of the animals. The daily clinical examination did not 
reveal any effects of BCD-085 on breathing pattern, motor activity, or sociability of the animals. 
The histological findings suggested that the test drug caused no local reactions in the 
administration site. 
The gross examination did not reveal any toxic effects of BCD-085 on organs or organ 
systems. In most cases, the morphological structure of the internal organs was consistent with 
animals’ age and normal histology. Most changes were seen also at baseline or could develop as 
spontaneous abnormalities during the study, which can be expected in captive-held animals.  
The toxicity study of BCD-085 (an anti-Il-17 mAb product, JSC BIOCAD) showed that 
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animals upon repeated-dose weekly subcutaneous administration over 25 weeks. The 
no-observed-adverse-effect-level (NOAEL) established in this study corresponded to the highest 
dose of BCD-085 (40 mg/kg). 
In the non-clinical study, animals tolerated BCD-085 well. The drug did not alter the 
cardiovascular and urinary function and did not produce any local intolerance. The drug was 
considered low-toxic and can be recommended for clinical development. 
1.3.1.2.6. Local tolerance studied as part of the BCD-085 repeated-dose toxicity 
Local tolerance was evaluated by external examination and histological findings. Tissues 
in the injection site and regional lymph nodes were taken for histology. 
Histological examination of the tissues taken after necropsy of animals in the main max 
dose group showed that BCD-085 40 mg/kg administered subcutaneously for 25 weeks did not 
produce any local intolerance in cynomolgus monkeys. Histological examination did not show any 
changes in the injection sites or draining lymph nodes. 
1.3.1.2.7. Immunotoxicity of BCD-085 
Repeated-dose immunotoxicity was studied using two doses of BCD-085: 8.0 mg/kg and 
40.0 mg/kg. The experiment was conducted in 9 male monkeys (Macaca fascicularis) of 3.0 kg to 
7.0 kg. The animals were divided into three groups depending on the dose/drug administered: 
1. BCD-085 8.0 μg/kg (3 males); 
2. BCD-085 40.0 μg/kg (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 showed that the test drug did not alter the subpopulation ratio. 
An assessment of drug effects on humoral immunity was one of the main parts of 
immunotoxicity study. 
The obtained results evidence that repeated SC administration of BCD-085 did not alter 
the levels and balance of immunoglobulins M, G, A, E. 
No changes in the phagocytic activity were observed during the study. Its intensity was 
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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 8.0 mg/kg and 40.0 mg/kg in cynomolgus monkeys 
produced no immunotoxicity in the said experimental settings. 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 


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1.3.1.2.11. 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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1.3.1.2.12. 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 2 mg/kg, 8 mg/kg, and 40 mg/kg (18 animals).  
The animals were divided into three groups according to drug doses assigned. 
BCD-085 was administered subcutaneously in the withers once a week for 25 weeks. This 
administration mode corresponds to one recommended for clinical use. The following doses were 
used in the study: 2 mg/kg, 8 mg/kg, and 40 mg/kg. The injection volume was 0.8 mL/kg. 
BCD-085 was administered at a dose of 2.5 mg/mL in the minimum dose group, 10.0 mg/mL in 
the medium-dose group, and 50.0 mg/mL in the maximum dose group. 
The potential effect of binding anti-BCD-085 antibodies on the PK parameters of the drug 
was assessed. Experimental findings confirmed that no animals developed anti-drug binding 
antibodies in any test group. 
1.3.2. Clinical studies 
By the time this Protocol was written, a Phase I clinical study was completed that 
investigated the safety, tolerability, and pharmacokinetics of single ascending doses of BCD-085. 
The results of this study are described below. BIOCAD also completed Phase II studies of the 
efficacy and safety of BCD-085 given as repeated SC injections of different doses in patients with 
moderate to severe plaque psoriasis and patients with ankylosing spondylitis. Study results are 
presented in section 1.3.2.2.2. Efficacy and safety of BCD-085. 
1.3.2.1. Dose-escalation single-dose study of pharmacokinetics, safety, and tolerability 
An open-label clinical study of the pharmacokinetics, tolerability, and safety of single 
ascending doses of BCD-085 in healthy volunteers 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: 


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1. Cohort 1: 1 volunteer who received a single SC dose of BCD-085 0.05 mg/kg of 
body weight. 
2. Cohort 02: 3 volunteers who received single SC doses of BCD-085 0.05 mg/kg of 
body weight. 
3. Cohort 03: 3 volunteers who received single SC doses of BCD-085 0.25 mg/kg of 
body weight. 
4. Cohort 04: 3 volunteers who received single SC doses of BCD-085 0.825 mg/kg of 
body weight. 
5. Cohort 05: 3 volunteers who received single SC doses of BCD-085 1.25 mg/kg of 
body weight. 
6. Cohort 06: 3 volunteers who received single SC doses of BCD-085 1.75 mg/kg of 
body weight. 
7. Cohort 07: 3 volunteers who received single SC doses of BCD-085 2.25 mg/kg of 
body weight. 
8. Cohort 08: 3 volunteers who received single SC doses of BCD-085 3.0 mg/kg of 
body weight. 
The volunteers were included in the study one after another. At first, 1 volunteer was 
included in Cohort 01 and received a single subcutaneous dose of BCD-085 0.05 mg/kg (estimated 
starting safe dose). If the volunteer 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 (DLT) 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 
complete blood count and blood chemistry) of grade 1 in 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 AST increased (1 
event in Cohorts 05 and 06) and ALT increased (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 included 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 the 








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products contain fully human monoclonal antibodies selective for interleukin-17, and the last one 
contains antibodies that target the IL-17 receptor. 
A Phase II clinical study of ixekizumab included 142 patients with moderate to severe 
psoriasis, who were randomized to 5 arms: 150 mg, 75 mg, 25 mg, and 10 mg of ixekizumab, and 
placebo. The test drug/placebo was administered at Weeks 0, 2, 4, 8, 12, and 16. The primary 
endpoint set as the proportion PASI 75 responders 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]. 
Two Phase III pivotal clinical studies, UNCOVER-2 and UNCOVER-3, were conducted 
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 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) were met 
in both studies with both regimens of ixekizumab therapy. In the UNCOVER-2 and UNCOVER-3 
studies, the PASI 75 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. 
 


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Table 5. Adverse reactions from the UNCOVER-2 and UNCOVER-3 studies. 
Adverse reactions 
Placebo, 
n=360 
Etanercept, 
n=739 
IX4W, 
n=729 
IX2W, 
n=734 
Any treatment-emergent AE 
44.2% 
53.9% 
57.5% 
57.4% 
SAE 
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 heterodimeric IL-17A/F cytokine. In a 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/placebo 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 given brodalumab, respectively. In the placebo arm, no PASI75 response was observed at 
all. The frequency of the response in all active 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 were 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 


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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 PASI 
75 responders 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 PASI 75 responders and sPGA 
responders. 
Table 6. Results from the AMAGINE-2 and AMAGINE-3 studies 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 maintained the PASI 75 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. 
The main adverse reactions registered in the AMAGINE-2 and AMAGINE-3 studies 
during the induction phase (first 12 weeks) are listed in Table 7. 


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Table 7. Adverse reactions registered in the AMAGINE-2 and AMAGINE-3 studies during the 
induction phase (first 12 weeks). 
Adverse reactions 
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% 
SAE 
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 infections 
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 reactions 
1.4% 
2.0% 
1.6% 
1.5% 
 
In November 2014, Amgen and AstraZeneca announced positive results from a Phase III 
study, 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 PASI 75 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 progression of the main disease, nasopharyngitis, and upper respiratory tract infections. 
Another Phase II study [20] used different 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 demand 
(“start of relapse” regimen). During the induction phase (Week 12), the proportion of PASI 75 
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 PASI 75 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% 
 
 
 
 


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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% 
 
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%, by arms, 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 reactions 
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% 
SAE 
1.8% 
1.2% 
2.1% 
0.9% 
Nasopharyngitis 
8.0% 
10.7% 
13.8% 
11.1% 
Upper respiratory tract infections 
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 infections 
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% 
 


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Thus, all three products blocking the signaling of interleukin-17 demonstrated high efficacy 
and a favorable safety profile in the clinical studies. 
1.3.2.2.2. Efficacy and safety of BCD-085 
By the date of this Protocol, two Phase II studies (in patients with plaque psoriasis and 
patients with ankylosing spondylitis), and extension periods (treatment extension to 1 year) of 
these studies have been completed.  
1.3.2.2.2.1. Results of the efficacy and safety study of BCD-085 in patients with psoriasis 
The first Phase II study (“An International, Multicenter, Randomized, Double-blind, 
Placebo-controlled, Dose-finding Clinical Study of the Efficacy and Safety of Subcutaneous 
BCD-085 in Patients with Moderate to Severe Plaque Psoriasis”) has now been completed. This 
study aimed at finding the optimal BCD-085 doses and treatment regimen for patients with 
moderate to severe plaque psoriasis and at investigating the efficacy, safety, and pharmacokinetics 
of BCD-085.  
According to the approved Protocol, the study involved 120 adults with moderate to severe 
plaque psoriasis. Before being included in the active phase of the study, all patients underwent a 
screening examination (max duration: 28 days) to determine whether they met the eligibility 
criteria. When all screening procedures were completed and the Investigator qualified the patient 
eligible for the study, the patient was stratified by body weight (≤80 kg/≥81 kg), prior use of 
monoclonal antibodies for the treatment of psoriasis (MAb-treated/MAb-naive), current use of 
systemic non-biologics (yes/no), PASI score (<20/≥20), and signs of psoriatic arthritis 
(absent/present). After stratification, the patients were randomized 1:1:1:1 to four study arms (Arm 
1: BCD-085 40 mg, Arm 2: BCD-085 80 mg, Arm 3: BCD-085 120 mg, Arm 4: placebo). Thus, 
the active period of the study involved the test drug/placebo injections given weekly for the first 
three weeks of treatment and then once every 2 weeks. After assessment of the results at Week 12, 
all patients were transferred to a 4-week follow-up. During 14 weeks after the screening, 9 visits 
were performed to assess the efficacy, safety, and immunogenicity of BCD-085. Patients involved 
in the PK study (a limited population) attended 13 visits. 
The treatment efficacy was assessed as a proportion of patients who achieved PASI 75 at 
Week 12 of treatment. The PASI 75 achievement was defined as at least 75% improvement in the 
overall PASI score at Week 12 versus baseline. 




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Assessment of PASI 50/75/90 achievement and relative changes in the PASI score showed 
that PASI score in the BCD-085 arms decreased significantly over time, with this reduction being 
significantly more pronounced than that in the placebo arm. Although there were no significant 
differences among the BCD-085 arms, the absolute values demonstrated the dose-dependent 
nature of the response. The highest proportions of all types of PASI achievers at Week 12 were 
seen in the arm dosed with BCD-085 120 mg. Similar trends were seen for the changes in the BSA 
and the proportion of patients with sPGA 0 or 1.  
The best response in terms of the NAPSI score and the itch severity was also seen with 
BCD-085 120 mg. Patients in this arm showed the best nail and itch improvement among all study 
arms.  
The quality of life assessment demonstrated the opposite results for two scores (SF-36 and 
DLQI). The DLQI score decreased gradually and significantly with time (which indicates an 
improvement in the QoL) in the BCD-085 arms and did not change in the placebo arm, while the 
SF-36 score (physical component) at Week 12 improved significantly in the placebo arm (with no 
inter-arm differences detected at all time points), and the mental SF-36 component improved 
significantly in Arm 1 (inter-arm comparison detected the difference only at Week 12). These 
findings are likely to be explained by the fact that the SF-36 is a nonspecific questionnaire used to 
assess the QoL in patients with various pathologies. This questionnaire is not tailored to diseases 
of any particular organs or systems, which may result in certain difficulties when interpreting 
patient responses with regard to psoriasis. At the same time, the DLQI is a validated dermatology-
specific instrument. Results obtained with the DLQI do not contradict the results obtained for other 
study endpoints. 
BCD-085 was proved superior to placebo. The primary study goal was achieved. Although 
there were no differences between three doses of BCD-085, the best overall reduction in the 
signs/symptoms of psoriasis was detected in the BCD-085 120 mg arm. 
The safety analysis included 117 patients. BCD-085 (all tested dose levels) demonstrated 
a favorable safety profile with adverse events not differing in nature and severity from those seen 
with placebo. 
At least one AE/SAE was reported in 45.16% (14 of 31) of patients in Arm 1, 36.67% (11 
or 30) of patients in Arm 2, 25.00% (7 of 28) of patients in Arm 3, and 39.29% (11 of 28) of 
patients in Arm 4 (P = 0.443, two-sided 𝜒𝜒2 test with Yates correction). AEs/SAEs were judged as 
related to the study treatment in 6 (19.35%) patients in Arm 1, in 3 (10.00%) patients in Arm 2, in 




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frequency of this case was 3.23% of all patients in Arm 1 (P = 1.000, two-sided Fisher’s exact 
test). 
BCD-085 40 mg, 80 mg, and 120 mg demonstrated a favorable safety profile. The nature 
and severity of adverse events seen in three BCD-085 arms did not significantly differ from that 
in the placebo arm. 
The immunogenicity assessment did not detect binding anti-BCD-085 antibodies in any 
patient. 
The PK analysis demonstrated dose-dependent changes in the BCD-085 concentration over 
time. The serum concentration of BCD-085 increased gradually in a linear mode and reached its 
maximum by the end of Week 1. With re-administrations, BCD-085 accumulated in the serum, 
and its concentration increased 
Higher doses (80 mg and 120 mg) showed higher 
induction potential as compared with 40 mg, because fewer injections were needed to achieve 
concentrations around Cmax-mult. This finding justified further investigation of a regimen with less 
frequent BCD-085 injections (once every 4 weeks). 
Thus, the study showed that BCD-085 40 mg, 80 mg, and 120 mg was significantly superior 
to placebo in patients with moderate to severe plaque psoriasis. The best response was observed 
in the arm treated with 120 mg BCD-085. 
1.3.2.2.2.2. Results of the extension period of the efficacy and safety study of BCD-085 in 
patients with psoriasis  
The extension period of the Phase II study aiming to assess the efficacy and safety of 
multiple SC doses of BCD-085 80 mg and 120 mg in patients with moderate to severe plaque 
psoriasis who completed the BCD‑085-2 study has been completed. 
The study involved 103 adult patients with moderate to severe plaque psoriasis who 
completed the BCD-085-2 study. After the investigator decided to include the patient in the study, 
PASI and its relative improvement vs. baseline for the BCD-085-2 study were determined. 
According to the results, the patient was distributed into one of two study arms:  
• 
120 mg arm (< PASI 50 vs. baseline). During the first 12 weeks of the BCD-085-2ext 
study, patients of this arm received BCD-085 120 mg subcutaneously (three injections 
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were mostly mild to moderate in severity (grade 1/2, CTCAE 4.03). No cases of treatment 
discontinuation due to AEs or SAEs were recorded. No injection site reactions were recorded after 
use of BCD-085. 
The immunogenicity analysis did not show binding anti-drug antibodies after 42 weeks of 
the BCD-085-2ext study (i.e. 56 weeks from the beginning of the BCD-085-2 study).  
Thus, the overall analysis demonstrated high efficacy of long-term use of BCD-085 in 
patients with moderate to severe plaque psoriasis who failed to respond to previous standard 
therapy. The maintenance treatment period showed that BCD-085 can be used less often (once a 
month) if administered at a dose of 120 mg. 
1.3.2.2.2.3. Results of the efficacy and safety study of BCD-085 in patients with ankylosing 
spondylitis 
The second Phase II study (“An International, Multicenter, Randomized, Double-blind, 
Placebo-controlled, Dose-finding Clinical Study of the Efficacy and Safety of Repeated-dose 
Subcutaneous BCD-085 in Patients with Active Ankylosing Spondylitis”) aimed at finding the 
optimal BCD-085 doses and treatment regimen for patients with active ankylosing spondylitis and 
at investigating the efficacy, safety, and pharmacokinetics of BCD-085 (BCD-085-3 study).  
According to the approved Protocol, the study involved 88 adults with active ankylosing 
spondylitis. Before being included in the active phase of the study, all patients underwent a 
screening examination (max duration: 28 days) to determine whether they met the eligibility 
criteria. After the patient completed the screening procedures and the Investigator qualified the 
patient eligible for the study, the patient was stratified according to the baseline CRP level 
(normal/elevated), BASDAI score (4-6/≥ 7), prior exposure to TNF-alpha inhibitors or other 
therapeutic monoclonal antibodies for the treatment of AS (experienced/naive), and need for 
DMARD therapy (yes/no). Stratified patients were then randomized 1:1:1:1 to 4 study arms (Arm 
1: BCD-085 40 mg, Arm 2: BCD-085 80 mg, Arm 3: BCD-085 120 mg, Arm 4: placebo). 
Thus, in the active phase of the study, patients were given injections of the test 
drug/placebo weekly for the first three weeks of treatment and then once every 2 weeks until Week 
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The secondary endpoint analysis showed that the ASAS20/40 and ASAS 5/6 rates at each 
assessment visit were higher in the BCD-085 arms than in the placebo arm. However, the pair-wise 
comparisons found these differences to be significant not for all assessment points. The most 
pronounced and quick changes were seen in patients receiving BCD-085 120 mg. This arm showed 
a significant superiority to placebo in ASAS40 and ASAS5/6 rates at Weeks 12 and 16.  
Similar results were obtained with other secondary endpoints. All assessed responses were 
higher in the BCD-085 arms than in the placebo arm, but the longest and fastest response was seen 
in the BCD-085 120 mg arm. In this arm, significant improvements in the BASDAI, ASDAS-CRP, 
BASMI, MASES, BASFI, CRP, and pain severity were seen as early as at the second assessment 
at Week 4 (for pain severity at Week 2). These improvements were maintained throughout the 
entire study, thus suggesting a significant decrease in the activity of ankylosing spondylitis.  
Changes in other endpoints (chest expansion) were less pronounced. However, 
improvements were seen for all endpoints, and they were the greatest with BCD-085 120 mg. 
BCD-085 was proved superior to placebo. The primary study goal was achieved. 
Comparison of additional efficacy measures at different timepoints showed that the most 
pronounced and fast response was achieved with BCD-085 120 mg. 
The safety analysis included 88 patients who received at least one dose of BCD-
085/placebo. BCD-085 (all tested dose levels) demonstrated a favorable safety profile with adverse 
events not differing in nature and severity from those seen with placebo. 
At least one AE/SAE was recorded in 45.45% (10) of patients in the BCD-085 40 mg arm, 
27.27% (6) of patients in BCD-085 80 mg arm, 18.18% (4) of patients in the BCD-085 120 mg 
arm and 31.82% (7) of patients in the placebo arm (P = 0.298, two-sided Fisher’s exact test). The 
arms did not differ in the proportion of patients with treatment-related adverse events (22.73%, 
18.18%, 4.55% and 22.73%, P = 0.354, two-sided exact Fisher’s test). 
The arms were also similar in the rates of severe AEs (grade 3/4), including those related 
to treatment (P > 0.05, two-sided Fisher’s exact test) 
There was only one dropout due to an AE. A patient from BCD-085 80 mg arm 
discontinued the study after Visit 6 due to the AE “erosive colitis” (CTCAE 4.03 grade 3), which 
was not related to the study therapy. No serious adverse events, injection site reactions or deaths 
were recorded. 




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1.3.2.2.2.4. Results of the extension period of the efficacy and safety study of BCD-085 in 
patients with ankylosing spondylitis  
The extension period of the Phase II study “An International, Multicenter, Randomized, 
Double-blind, Placebo-controlled, Dose-finding Clinical Study of Efficacy and Safety of 
Repeated-dose Subcutaneous BCD-085 in Patients with Active Ankylosing Spondylitis” aimed to 
compare the efficacy and safety of multiple subcutaneous doses of BCD-085 80 mg and 120 mg 
in patients with active ankylosing spondylitis who completed the BCD-085-3 study. 
BCD-085-3ext study (“An International, Multicenter, Open-label, Comparative Clinical Study of 
the Efficacy and Safety of Multiple Subcutaneous Doses of BCD‑085 80 mg and 120 mg in 
Patients with Ankylosing Spondylitis Who Completed the BCD‑085-3 Study”). 
The study involved 81 adult patients with ankylosing spondylitis who completed the 
previous study BCD-085-3. On the basis of ASAS20 response (vs. screening for BCD-085-3 
study), the patients were distributed into two arms: 
• 
Arm 1: patients who achieved ASAS20 by Week 16 of the BCD-085-3 study. In 
the extension study, they received BCD-085 80 mg subcutaneously (2.0 mL) once every 2 weeks 
through Week 36 (52).  
• 
Arm 2: patients who failed to achieve ASAS20 by Week 16 of the BCD-085-3 
study. In the extension study, they received BCD-085 120 mg subcutaneously once every 2 weeks 
through Week 36 (52). 
More than 70% of patients achieved ASAS response (ASAS20/40, ASAS5/6) at each 
assessment point (Weeks 28, 40, 52) during the extension study regardless of the dose used. 
Other endpoints in the total population (n=81) demonstrated similar trends: a statistically 
significant improvement achieved by the first assessment point of the extension study [Week 12 
(28)], then a stable response that maintained without changes through the study end. 
The analysis of the ASAS20/40 rate over time did not detect trends towards a loss of 
response during the extension study. By the end of the extension study, only 7.41% (4) of patients 
(ASAS20) and 10.26% (4) of patients (ASAS40) lost their response achieved after 16 weeks of 
the main study BCD-085-3. 
The extension period showed that the long-term use of BCD-085 120 mg resulted in a 
pronounced clinical response in patients who failed to respond during the first 16 weeks of the 




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and infestations and blood and lymphatic system disorders. Cardiovascular and hepatobiliary 
disorders were less common. 
Most adverse events, including treatment-related ones, were mild to moderate (CTCAE 
4.03 grade 1/2), thus suggesting a favorable safety profile of BCD-085. Four patients had severe 
grade 3 adverse events (neutropenia, GGT increased, ARVI and blood pressure increased). The 
vast majority of treatment-related adverse events were expected and mild to moderate.  
Two cases of positive Diaskintest with normal chest X-ray were recorded during the study. 
It should be noted that no active tuberculosis infection was recorded in the study subjects with 
positive Diaskintest results during the study. Special attention should be paid to AE “esophagus 
candidiasis” recorded in one patient (1.23%). Candida infections of various localization, in 
particular, esophagus, have been described for interleukin-17 blockers. These events are classified 
as adverse events of special interest. In the extension study, esophagus candidiasis was of grade 2 
and resolved without sequelae after a medication therapy.  
If considering the route of administration (SC injections), injection site reactions are 
expected for BCD-085. The proportion of patients with injection site reactions was 1.23% (one 
patient had two local reactions, which included hyperemia, swelling, itch, pain and local infiltrate). 
This shows a low incidence rate of this AE.  
To assess the risk of increasing AE/SAE rate during the long-term use of BCD-085, 
exposure-adjusted AEs incidence rate (EAIR) was assessed during the extension phase and 
compared with that during the BCD-085-3 study. The EAIR for the BCD-085-3 study was 1.379, 
for the BCD-085-3ext – 0.588. Thus, the frequency of AE/SAE showed a tendency towards a 
decrease during the long-term use, suggesting no risk of AE rate increase over time. 
The immunogenicity assessment did not detect binding anti-BCD-085 antibodies in any 
patient. 
Thus, the obtained data confirmed the high efficacy of BCD-085 (JSC BIOCAD, Russia) 
in ankylosing spondylitis. The response was stable over time; it was more frequent with BCD-085 
120 mg. The safety profile of BCD-085 was favorable. 
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 significant progress in the development of treatment options, severe 
atypical forms resistant to therapy have become more common in the last decade. Biologics 


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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 skin damage. Taking this information into account, 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 was confirmed in a number of 
clinical studies. 
JSC BIOCAD has developed an original monoclonal anti-IL-17 antibody (BCD-085), which 
has several competitive advantages over other drugs of this class. BCD-085 has modified Fc 
regions and CDRs,
 
respectively.  
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 
and potency. A set of experiments in relevant animal species (cynomolgus monkeys) 
 
demonstrated the pharmacodynamic effect of BCD-085, which is 
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 of a large non-clinical program allowed for conducting a Phase I clinical study in 
healthy volunteers and Phase II studies in patients with moderate to severe plaque psoriasis and in 
patients with active ankylosing spondylitis. BCD-085 confirmed the previously discovered 
characteristics such as high efficacy and favorable safety profile. Pharmacokinetics of BCD-085 
was typical for monoclonal antibodies. The drug was shown to have a long half-life period. The 
Phase II studies showed that upon repeated injections of BCD-085 40 mg, 80 mg, and 120 mg, the 
minimum serum concentration was rather high (> 60% Cmax) and was reached before the second 
injection of BCD-085. With re-administrations, BCD-085 accumulated in the serum, and its 
concentration increased 
 Higher doses (80 mg and 120 mg) showed higher induction 
potential as compared with 40 mg because fewer injections were needed to achieve concentrations 
around Cmax-mult. Thus, it was decided to assess a less frequent dosing regimen (once every 4 weeks 
after induction). 
Thus, BCD-085 can be recommended for further clinical development in the target 
populations of patients. With the current knowledge from clinical studies of other drugs having 


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similar mechanisms of action, psoriasis is believed to be highly sensitive to IL-17 blockade. 
Investigating this drug 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. 
1.4. Summary of the known and potential risks and benefits, if any, to human subjects 
(risk/benefit balance) 
1.4.1. Benefit assessment 
BCD-085 is an innovative drug the toxicity, safety, and pharmacokinetics of which was 
investigated in animals, in the Phase I clinical study in healthy volunteers, and in the Phase II 
clinical studies in patients with moderate to severe plaque psoriasis and in patients with ankylosing 
spondylitis. 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. This 
clinical study aims at investigating the efficacy and safety of a less frequent dosing regimen of 
BCD-085 (once every 4 weeks) versus BCD-085 every 2 weeks and versus placebo in patients 
with moderate to severe plaque psoriasis. This means that some study subjects will be randomly 
assigned to the placebo arm during the first period of the study and, thus, may not get any personal 
benefit from being in the study other than getting a comprehensive medical examination. However, 
the information obtained after the study is completed will be of high scientific value and may help 
to implement in clinical practice a new effective treatment for autoimmune diseases. At the end of 
this period, all patients (including those from the placebo arm) will be switched to BCD-085, which 
should result in good treatment response. If the study achieves its primary endpoint, BCD-085 will 
be administered less frequently (and thus more conveniently for patients). 
1.4.2. Risk assessment 
BCD-085 is a new drug, so its effects in humans are not enough investigated. The 
pharmacodynamic effects of blocking human IL-17 suggest 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); during the study potential complications will 


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be carefully monitored. Thus, it is expected that the risk of infectious complications for the patients 
involved in the study will be minimal. Risk of allergic reactions cannot be ruled out in subjects 
with hypersensitivity to ingredients of BCD-085. The method of administration (subcutaneous 
injections) and protein nature of BCD-085 suggest that there is a risk of injection site reactions. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
The 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) were rarely 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 


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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. 
In one Phase II clinical study, SC injections of BCD-085 40 mg, 80 mg, and 120 mg in 
patients with moderate to severe plaque psoriasis were well tolerated; no serious adverse events or 
grade 4 adverse events were reported. Nobody withdrew from the study due to adverse events. The 
most common AEs were neutropenia, acute respiratory tract infections, increased blood pressure, 
and elevated liver transaminases. Most of the AEs were mild in severity. Only one injection site 
reaction (grade 1) was detected in Arm 1 manifesting as swelling in the injection site. The 
investigator did not consider this event clinically meaningful. 
Another Phase II clinical study showed that BCD-085 at doses of 40 mg, 80 mg, and 120 
mg has a favorable safety profile in patients with ankylosing spondylitis. The vast majority of 
adverse events were represented by single episodes throughout the entire study. The most common 
adverse events were infections and blood and lymphatic system disorders. Cardiovascular 
disorders were slightly less common. Most adverse events, including treatment-related ones, were 
mild or moderate in severity (CTCAE 4.03 grade 1/2). Grade 3/4 AEs were registered as single 
episodes in all arms including the placebo arm. Thus, the safety profile of BCD-085 was 
considered favorable. No SAEs were reported in this study. The immunogenicity assessment did 
not detect binding anti-BCD-085 antibodies in any patient. 
1.4.3. Conclusions 
Findings from physicochemical investigation, non-clinical development, the clinical study 
of PK, safety, and tolerability in healthy volunteers, the clinical studies of the efficacy and safety 
of multiple SC injections of different doses of BCD-085 in patients with moderate to severe plaque 
psoriasis and in patients with ankylosing spondylitis provided 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 development program, including that in patients with 
psoriasis, will have a positive effect with low risk of adverse reactions. Thus, the overall 
risk/benefit ratio for BCD-085 is considered favorable for the patients.  


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1.5. Description of and justification for the route of administration, dosage, dosing regimen, 
and treatment period 
1.5.1 Description and justification of the study design 
This is an international multicenter double-blind randomized study to compare the efficacy 
and safety of two dosing regimens of BCD-085 (JSC BIOCAD, Russia) in patients with moderate 
to severe plaque psoriasis in 3 parallel arms [Arm 1: BCD-085 120 mg Q2W after induction; Arm 
2: BCD-085 Q4W after induction; Arm 3: placebo (until Week 10), blinded therapy]. At Week 12, 
the therapy will be unblinded, and the efficacy will be assessed. Starting from Week 14, patients 
in Arm 1 will receive BCD-085 Q4W through Week 50. Starting from Week 14, patients in Arm 
2 will continue to receive BCD-085 Q4W through Week 50. Patients from Arm 3 will receive 
BCD-085 at Weeks 12, 13 and 14, then Q4W (from Week 18 through Week 50). To assess long-
term efficacy and safety of BCD-085, and to evaluate maintenance of the stable treatment effect 
with no increased safety risk after 1-year treatment, the treatment in ≥PASI 75 responders at Week 
52 will be continued Q4W starting from Week 54 through Week 154 (in patients from Arms 1 and 
2) or through Week 166 (in patients from Arm 3). 
Since the planned population size is 213 patients with moderate to severe plaque psoriasis, 
it is unlikely that all of them can be recruited at one study site. To ensure optimal timing, patients 
will be recruited at several sites. 
In this study, the effects of BCD-085 will be compared with the effects of placebo to make 
adequate and objective conclusions on the efficacy and safety of BCD-085. The necessity of using 
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 minimize 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. 
Patients in all three arms will receive the treatment in parallel. This is important to obtain 
objective results and eliminate the possibility of external factors to affect treatment efficacy and 
safety. It is known, for example, that psoriasis patients commonly have seasonal exacerbations, 
and by using the parallel-group design, the effect of the season on the study results will be 
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Randomization ensures that any factors that can affect treatment results are uniformly 
distributed by study groups, thus allowing to attribute differences in responses directly to the 
investigational product used. 
This Phase III study aims to evaluate the efficacy and safety of BCD-085 Q4W vs. BCD-085 
Q2W vs. placebo in patients with moderate to severe plaque psoriasis and to investigate long-term 
efficacy and safety of BCD-085 in this population. In drug development, treatment duration should 
be enough to establish the efficacy and safety of the drug but should not be too long because some 
patients are on placebo. The EMA guidelines [CHMP/EWP/2454/02 corr, 2004] 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]. It was decided to use a less frequent 
dosing regimen on the basis of the assessment of multiple-dose PK in the Phase II study. It showed 
that with repeated administrations BCD-085 accumulated in serum, and its concentrations 
increased several times. Thus, BCD-085 can be used less frequently after the induction period.  
The primary endpoint in 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 
PASI 75 responders is widely used in clinical development to evaluate the efficacy of psoriasis 
drugs and is also 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 was used in Phase III 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 static 
Physician’s Global Assessment (sPGA), Nail Psoriasis Severity Index (NAPSI), 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]. NAPSI was used in several Phase 3 studies of 
ixekizumab (an anti-IL-17 antibody) (RHAZ, RHBA studies18). It significantly improved in 
patients with psoriatic nail involvement.  
                                                          
18 http://www.ema.europa.eu/docs/en GB/document library/EPAR -
Public assessment report/human/003943/WC500205806.pdf  


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The recent findings suggest that interleukin-17 plays a key role in the development of 
psoriasis. Clinical studies of drugs blocking the IL-17 signaling (ixekizumab, brodalumab, and 
secukinumab) demonstrated high efficacy of this approach in the treatment of patients with 
moderate to severe plaque psoriasis with the PASI 75 response seen in 70% to 80% of patients as 
early as after 12 weeks of treatment [15-21]. Thus, moderate to severe plaque psoriasis is 
considered a model sensitive enough for clinical investigation of BCD-085. 
1.5.2. Description of and justification for the route of administration, dosage, dosing regimen, 
and treatment period 
In Arm 1, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment), then Q2W through Week 10. After that, since Week 14, patients will receive 
BCD-085 Q4W through Week 50. If achieving ≥PASI 75 response at Week 52, patients will 
receive treatment with BCD-085 Q4W from Week 54 through Week 154.  
In Arm 2, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment) and then Q4W (maintenance treatment) through Week 10. Thus, the drug 
will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction therapy), 
Day 1 of Week 6, Day 1 of Week 10. To maintain the study blind, patients of this arm will receive 
placebo (2 injections) on Day 1 of Week 4 and Week 8. Starting from Week 14, patients will 
receive BCD-085 Q4W through Week 50. If achieving ≥PASI 75 response at Week 52, patients 
will receive treatment with BCD-085 Q4W from Week 54 through Week 154. 
In Arm 3 (control arm), patients will receive 2 subcutaneous injections of placebo (1.0 mL 
each) on Day 1 of Weeks 0, 1, 2, 4, 6, 8 and 10. Patients will receive BCD-085 120 mg once a 
week at Weeks 12, 13, 14, then Q4W starting from Week 18 through Week 50. If achieving ≥PASI 
75 response at Week 52, patients will receive treatment with BCD-085 Q4W from Week 54 
through Week 166. 
Patients will be followed up for 4 weeks after the last injection of the investigational product. 
BCD-085 is a potential therapeutic candidate for the long-term management of psoriasis. In 
the Phase II clinical study of the efficacy and safety of different doses of BCD-085, the drug was 
used as SC injections for better convenience of the patients because this route of administration 
has several advantages. Patients can give injections to themselves, or injections can be made in the 


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outpatient settings. Thus, it is reasonable to study the efficacy, safety, and immunogenicity of 
BCD-085 in patients with the same route of administration that is planned to be implemented in 
routine clinical practice. 
 
 
 
 
 
 
 
 
 
 
The main PK parameters of BCD-085 were characterized in the Phase I study. This study 
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 studies”).  
It was shown that doses closest to those planned to be used in the Phase II study were given 
to patients from Cohorts 4-6 (with account for patients’ body weight). Thus, it was considered that 
BCD-085 40 mg, 80 mg, and 120 mg will have pharmacokinetics similar to that seen in Cohorts 
4-6 with the half-life ranging from 16 to 18 days. Thus, the Phase I of the clinical development 
allowed suggesting that BCD-085 should be used once every 2 weeks.  
However, the PK study in the Phase II of the clinical development in patients with psoriasis 
showed that with re-administrations, BCD-085 accumulated in the serum, and its concentration 
increased 
 Higher doses (80 mg and 120 mg) showed higher induction potential as 
compared with 40 mg because fewer injections were needed to achieve concentrations around 
Cmax-mult. Thus, it was decided to assess a less frequent dosing regimen (once every 4 weeks after 
induction). Less frequent dosing with the same treatment efficacy will allow a more comfortable 
and safe dosing regimen for the patients. At baseline, patients have acute inflammation that has to 
be resolved as soon as possible. This requires induction (higher) doses or an induction phase (more 
frequent injections). Clinical studies of the drugs inhibiting the signaling of interleukin-17 utilized 
both the first [16] and the second [17, 18, 20, 21] approaches. In this study, patients will receive 


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BCD-085 once weekly for 3 weeks for induction treatment. After that, patients will be switched 
to maintenance doses of BCD-085 (Arm 1: Q2W, after 10 weeks – Q4W; Arm 2: Q4W after 
induction). Patients of Arm 3 will receive BCD-085 at Weeks 12, 13, and 14, then Q4W (Week 
18 through Week 50). To assess long-term efficacy and safety of BCD-085, and to evaluate 
maintenance of the stable treatment effect with no increased safety risk after 1-year treatment, the 
treatment in ≥PASI 75 responders at Week 52 will be continued Q4W starting from Week 54 
through Week 154 (in patients from Arms 1 and 2) or through Week 166 (in patients from Arm 
3). 
Thus, the 120 mg dose, dosing frequency, and route of administration to be used in this 
study were chosen on the basis of the findings from non-clinical and phase I and II clinical studies 
of BCD-085 and available information on other anti-IL-17 monoclonal antibodies. Convenience 
for patients was also taken into account. 
1.5.3. Justification of placebo use 
Some of the patients 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 [15-22]. The necessity of using placebo in this 
case 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 not be exposed to excessive risk because of getting a 
placebo. If the disease worsens and requires additional therapy, the patient can always discontinue 
the study and receive all the medications he/she needs.  
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. 
1.6. Clinical study compliance with regulatory requirements 
The clinical study will be conducted according to this Protocol developed in full compliance 
with the current law of the Russian Federation, Federal Law No. 61-FZ of April 12, 2010: On the 
Circulation of Medicines; National Standard of the Russian Federation GOST R 52379-2005 Good 
Clinical Practice; the rules of Good Clinical Practice of the Eurasian Economic Union; the 
Constitution of the Russian Federation; Federal Law No. 323-FZ of November 21, 2011: On 


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Public Health Protection in the Russian Federation; the WMA Declaration of Helsinki (Fortaleza 
2013), Order No. 200n of April 01, 2016 On Approval of the Good Clinical Practice; the GCP 
principles, and the current law and regulations of the participating countries. 
1.7. Description of study population 
Men and women aged from 18 years (inclusive) and older with a confirmed diagnosis of 
moderate to severe plaque psoriasis (lasting for at least 6 months before signing the ICF) who did 
not respond to/are 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 Jun; 160(4): 810–820.  
2. Nestle FO, Kaplan DH, Barker J. Psoriasis 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. Clin Dermatol 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 Invest Dermatol 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 
Leukoc Biol 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 Invest 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. 
Clin Dermatol 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. J 
Invest 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 Exp 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 Immunol 2008;180:1913-20. 
15. Gordon KB, Blauvelt A, Papp KA et al, Phase 3 Trials of Ixekizumab in Moderate-to-
Severe Plaque Psoriasis, N Engl J Med. 2016 Jul 28;375(4):345-56. doi: 
10.1056/NEJMoa1512711. Epub 2016 Jun 8. 
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. Benjamin Farahnik, Kourosh Beroukhim et al, Brodalumab for the Treatment of Psoriasis: 
A Review of Phase III Trials, Dermatol Ther (Heidelb) (2016) 6:111–124 DOI 
10.1007/s13555-016-0121-x. 
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. 


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19. Langley RG1, Elewski BE, et al, Secukinumab in plaque psoriasis - results of two phase 3 
trials, N Engl J Med. 2014 Jul 24;371(4):326-38. doi: 10.1056/NEJMoa1314258. Epub 
2014 Jul 9. 
20. Rich P, Sigurgeirsson B, Thaci DP, et al. Secukinumab induction and maintenance therapy 
in moderate-to-severe plaque psoriasis: a randomised, double-blind, placebo-controlled, 
phase II regimen-finding 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 24;371(4):326-38. 
22. Kircik L, Fowler J, Weiss J, Meng X, Guana A, Nyirady J. Efficacy of Secukinumab for 
Moderate-to-Severe Head and Neck Psoriasis Over 52 Weeks: Pooled Analysis of Four 
Phase 3 Studies. Dermatology and Therapy. 2016; 6(4):627-638. doi:10.1007/s13555-016-
0139-0.  
23. Menter A, Cather JC, Jarratt M, Meng X, Guana A, Nyirady J. Efficacy of Secukinumab 
on Moderate-to-severe Plaque Psoriasis Affecting Different Body Regions: a Pooled 
Analysis of Four Phase 3 Studies. Dermatology and Therapy. 2016; 6(4):639-647. 
doi:10.1007/s13555-016-0140-7. 
24. Thaçi D, Blauvelt A, Reich K, Tsai TF, Vanaclocha F, Kingo K, Ziv M et al. Secukinumab 
is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque 
psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015 
Sep;73(3):400-9. doi: 10.1016/j.jaad.2015.05.013. Epub 2015 Jun 17 
25. Kavanaugh A. Ethical and practical issues in conducting clinical trials in psoriasis and 
psoriatic arthritis.Ann Rheum Dis 2005;64:ii46-ii48. 
26. 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. 
27. Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J 
Dermatol. 2012 Oct;167(4):717–24. 
28. 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 Sept;129(9):2175–83. 


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29. Girolomoni G, Mrowietz U, Paul C. Psoriasis: rationale for targeting interleukin-17. Br J 
Dermatol. 2012 Oct;167(4):717–24. 
30. 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. 
31. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 
2009 Aug 27;361(9):888–98. 
32. Federal law 61-FZ dated 12.04.2010 “Concerning the circulation of medicinal products”. 
33. 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). 
34. Order No. 200n of April 01, 2016: On Approval of the Good Clinical Practice Rules. 


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2. STUDY AIMS AND OBJECTIVES 
2.1 Study aims 
Study aim: To evaluate the efficacy and safety of BCD-085 Q4W vs. BCD-085 Q2W (standard 
dosing regimen) vs. placebo. 
2.2 Study objectives 
Objectives of the main study period 
1. To compare the efficacy of BCD-085 in two dosing regimens and placebo using PASI 75 
rate, sPGA score, and other secondary efficacy measures after 12 weeks of the treatment. 
2. To compare the efficacy of BCD-085 in two dosing regimens and placebo using PASI 75 
rate, sPGA score, and other secondary efficacy measures after 52 weeks of the treatment. 
3. To evaluate the proportion of patients in each study arm who developed adverse events with 
repeated administration of BCD-085 or placebo. To compare the safety profiles of BCD-
085 Q4W and BCD-085 Q2W. 
4. To assess the immunogenicity of BCD-085 defined as the proportion of patients who 
developed anti-drug antibodies (binding/neutralizing). 
Objectives of the extension study period 
1. To assess maintenance of response during the long-term treatment with BCD-085 (for up 
to 154 weeks) and evaluate the safety profile of such treatment. 
2. To assess the immunogenicity of BCD-085 defined as the proportion of patients who 
developed anti-drug antibodies (binding/neutralizing). 
3. STUDY HYPOTHESIS 
Two independent hypotheses will be tested during the study: 
1. BCD-085 Q4W is not less effective than BCD-085 Q2W; 
2. The efficacy of BCD-085 in both regimens is superior to placebo. 


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4. STUDY DESIGN 
4.1. Primary and secondary outcome measures to be assessed in the study 
4.1.1. Primary endpoint 
• Proportion of patients who achieved PASI 75 at Week 12, by study arms. 
4.1.2 Secondary endpoints 
Efficacy endpoints during the main study period (Week 0 through Week 54): 
• Proportion of patients who achieved PASI 75/90/100 at Weeks 8, 16, 24, 42 and 
52, by study arms.  
• Proportion of patients with sPGA score 0 or 1 at Weeks 8, 12, 16, 24, 42, and 52. 
• Proportion of patients with sPGA score 0 at Weeks 16, 24, 42, and 52. 
• Relative change from baseline in PASI score at Weeks 8, 12, 16, 24, 42 and 52. 
• Change from baseline in itch severity measured with visual analog scale (0 mm to 
100 mm) at Weeks 1, 12, 24, and 52. 
• Change from baseline in Nail Psoriasis Severity Index (NAPSI) score at Week 12, 
24, and 52. 
• Change from baseline in Dermatology Life Quality Index (DQLI) score at Weeks 
8, 12, 24, 42, and 52. 
• Proportion of patients with DLQI score 0 or 1 at Weeks 24, 42, and 52. 
• Proportion of patients (among those with psoriatic arthritis) who achieved an 
ACR20/50/70 at Weeks 12, 24, and 52. 
Efficacy endpoints during the extension study period (Week 54 through Week 166) 
• Proportion of patients who maintained PASI 75/90/100 response after 62, 74, 86, 
98, 110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 
• Proportion of patients who maintained sPGA 0-1 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 


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• Proportion of patients who maintained sPGA score 0 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 
• Proportion of patients who maintained DLQI score 0-1 after 62, 74, 86, 98, 110, 
122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of treatment 
with BCD-085. 
• Time to loss of PASI 75/90/100, sPGA 0-1/sPGA 0, DLQI 0-1 response during 
the treatment with BCD-085. 
• Proportion of patients who maintained ACR 20/50/70 response (among patients 
with psoriatic arthritis) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of 
treatment vs. response after 52 weeks of treatment with BCD-085. 
• Proportion of patients who achieved PASI 75/90/100 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment with BCD-085. 
• Proportion of patients with sPGA score 0 or 1 after 62, 74, 86, 98, 110, 122, 134, 
146, and 154 weeks of the treatment with BCD-085. 
• Proportion of patients who achieved sPGA score 0 after 62, 74, 86, 98, 110, 122, 
134, 146, and 154 weeks of treatment with BCD-085. 
• Change from baseline in itch severity measured with visual analog scale (0 mm to 
100 mm) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment with 
BCD-085. 
• Change from baseline in Nail Psoriasis Severity Index (NAPSI) score after 62, 74, 
86, 98, 110, 122, 134, 146, and 154 weeks of treatment with BCD-085 (among 
patients with nail psoriasis at baseline). 
• Proportion of patients who achieved DLQI score 0 or 1 after 62, 74, 86, 98, 110, 
122, 134, 146, and 154 weeks of treatment with BCD-085. 
• Change from baseline in Dermatology Life Quality Index (DQLI) score after 62, 
74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment with BCD-085. 
Safety endpoints: 
• 
Proportion of patients who developed AEs/SAEs. 
• 
Proportion of patients who developed injection site reactions. 
• 
Proportion of patients who developed Grade 3/4 AEs/SAEs. 


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• 
Proportion of patients who discontinued the study due to AEs and/or SAEs. 
• 
Exposure adjusted incidence rate of AEs/SAEs during the extension study.  
Immunogenicity endpoints 
• 
Proportion of patients with anti-drug antibodies (binding/neutralizing). 
4.2. Description of the study type/design, study flow-chart, study procedures and periods 
Study design 
The BCD-085-7 study is an international multicenter, randomized, double-blind, 
placebo-controlled clinical study comparing the efficacy and safety of two dosing regimens of 
BCD-085 (JSC BIOCAD, Russia) in patients with moderate to severe plaque psoriasis. 
Before being screened for the study, patients must read and sign the informed consent form 
and undergo a screening examination (within 28 calendar days) to confirm that they are eligible 
for the study. The Protocol does not provide any additional requirements regarding the diet or 
physical activity during the screening or study period. The study is planned to enroll 213 adult 
patients with moderate to severe plaque psoriasis (diagnosed at least 6 months before signing the 
informed consent form) who have BSA ≥ 10%, PASI score ≥ 10, 19and sPGA score ≥ 3. 
Stratification and randomization 
When the Investigator has decided that the patient can take part in the study, the patient 
should be stratified according to his/her body weight (<100 kg/≥100 kg), previous use of 
monoclonal antibodies for the treatment of psoriasis (previously treated/naive), PASI score 
(<20/≥20), and psoriatic arthritis (yes/no) and randomly assigned at a 2:2:1 ratio to one of the three 
study groups: 1) BCD-085 Q2W (Arm 1), 2) BCD-085 Q4W (Arm 2), 3) placebo (Arm 3). 
Study periods 
1. Screening (up to 28 days from signing the Patient Information Sheet with the Informed 
Consent Form, inclusive); 
2. Main treatment period (from Week 0 through Week 54  
                                                          
19 The severity of psoriasis must be confirmed by the investigator at screening. 


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3. Extension treatment period (from Week 54 through Week 154 in Arms 1 and 2, from 
Week 54 through Week 166 in Arm 3); 
4. Follow-up period (from Week 154 through Week 158 in Arms 1 and 2, from Week 166 
through Week 170 in Arm 3). 
Screening period:  
Up to 28 days from signing the Patient Information Sheet with the Informed Consent Form, 
inclusive. 
 
Main study period (Week 0 to Week 54) 
In this study period patients will be distributed to three arms: 
• Arm 1: Patients in this arm (85 subjects) will receive BCD-085 120 mg (two subcutaneous 
injections, 60 mg in 1.0 mL each) once a week during the first 3 weeks (induction) and 
then once every 2 weeks through Week 10. Thus, the investigational product will be 
administered on Day 1 of Week 0, Week 1, Week 2, Week 4, Week 6, Week 8, and Week 
10.  
• Arm 2: Patients in this arm (85 subjects) will receive BCD-085 120 mg (two subcutaneous 
injections, 60 mg in 1.0 mL each) once a week during the first 3 weeks (induction) and 
then once every 4 weeks through Week 10. Thus, the investigational product will be 
administered on Day 1 of Week 0, Week 1, Week 2, Week 6 and Week 10. To maintain 
the study blind, patients of this arm will receive placebo (2 injections) on Day 1 of Week 
4 and Week 8. 
• Arm 3: Patients of this arm (43 subjects) will receive placebo (2 subcutaneous injections 
of placebo, 1.0 mL each) on Day 1 of Week 0, Week 1, Week 2, Week 4, Week 6, Week 
8 and Week 10. 
On Week 12, the treatment efficacy will be assessed with a PASI 75 score, and the 
treatment will be unblinded. Patients from Arms 1 and 2 will be given BCD-085 once every 4 
weeks. Patients from Arm 3 will receive BCD-085 as follows:  
 Induction: Weeks 12, 13, and 14, once a week;  
 Weeks 18 through 50: once every 4 weeks. 


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Therefore, there will be 3 arms even after unblinding, and patients will receive BCD-085 
according to the regimens described below: 
a) Patients in Arm 1 will receive BCD-085 120 mg (2 SC injections of 60 mg each) once 
every 4 weeks starting from Week 14 and through Week 50. 
b) Patients in Arm 2 will receive BCD-085 120 mg (2 SC injections of 60 mg each) once 
every 4 weeks starting from Week 14 and through Week 50. 
c) Patients in this arm will receive BCD-085 120 mg once a week at Weeks 12, 13, 14, then 
once every 4 weeks through Week 50. 
Unblinding will be performed at Visit 8 (Week 12) by opening the randomization envelops 
provided by the Sponsor with the investigational products. 
Extension study period (from Week 54 through Week 154 for Arms 1 and 2, through 
Week 166 for Arm 3): 
During the extension study period (Week 54 to Week 166) all patients who achieved PASI 
75 at Week 52 will receive BCD-085 120 mg once every 4 weeks: 
a) Patients from Arm 1 will receive BCD-085 from Week 54 through Week 154. 
b) Patients from Arm 2 will receive BCD-085 from Week 54 through Week 154. 
c) Patients from Arm 3 will receive BCD-085 from Week 54 through Week 166. 
Patients who fail to achieve PASI 75 at Week 52 will be withdrawn from the study. 
The investigator must inform JSC BIOCAD within 24 h about the patient’s premature 
withdrawal and specify the reason (by email). 
If the subject discontinues the study, an Early Withdrawal Form should be filled out in the 
CRF. The follow-up procedures for the discontinued subjects are described in section 5.4 
Procedures by Visits. 
Patients who discontinue the study will not be replaced. 
For further details see Section 11.6. Study termination. 
In Arm 3, treatment will be extended by 12 weeks so that the total treatment duration in all 
arms can be 154 weeks. During the main treatment period (during the first 12 weeks of the study), 
patients from Arm 3 receive placebo, so the treatment period for these patients is extended to 166 
weeks. 


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Regardless of the arm where the patient is assigned to, during the main study period (Week 
0 through Week 54) SC injections will be performed by an authorized member of the study team 
at the study site (except for the injection on Week 54).  
At Week 54 patients will be trained on how to self-inject the investigational product. If 
necessary, the training can be repeated at any of the subsequent visits. 
During the extension study period (Week 54 to Week 154 for patients from Arms 1 and 2, 
Week 54 to Week 166 for patients from Arm 3), patients will self-inject the investigational product 
at home (on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 138, 142, 
150 in Arms 1 and 2; on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 
138, 142, 150, 158, 162 in Arm 3) after relevant training at the study site at Week 54. Injections 
of the investigational product on visit dates will be performed by an authorized member of the 
study team at Weeks 62, 74, 86, 98, 110, 122, 134, 146, 154 (in Arms 1 and 2) or at Weeks 62, 74, 
86, 98, 110, 122, 134, 146, 154, 166 (in Arm 3). The first self-injection of the investigational 
product at Week 54 will be performed under the supervision of an authorized member of the study 
team. 
Frequency of visits during the extension study period will be the following: 
• For patients of Arms 1 and 2: once every 8 weeks (from Week 54 through Week 62), then 
once every 12 weeks (from Week 62 through Week 146), with the last treatment visit at 
Week 154. 
• For patients of Arm 3: once every 8 weeks (from Week 54 through Week 62), once every 
2 weeks (from Week 62 through Week 64), once every 10 weeks (from Week 64 through 
Week 74), once every 12 weeks (from Week 74 through Week 146), once every 8 weeks 
(from Week 146 through Week 154), with the last treatment visit at Week 166. 
At each of the visits from Week 54 to Week 146 (for Arms 1 and 2) or to Week 154 (for Arm 3), 
BCD-085 will be dispensed to patients for self-administration at home at an amount sufficient 
until the next visit.  
 
Follow-up period (4 weeks) 
Patients will be followed up for 4 weeks after the last injection (Week 154 to Week 158 for 
Arms 1 and 2, Week 166 to Week 170 for Arm 3). 
 




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Treatment by study arms 
In Arm 1, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment) and then once every 2 weeks through Week 10 (inclusive). After 10 weeks, 
patients will receive BCD-085 once every 4 weeks starting from Week 14 through Week 50. If 
achieving ≥PASI 75 response at Week 52, patients will receive treatment with BCD-085 Q4W 
from Week 54 through Week 154. 
In Arm 2, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment) and then Q4W (maintenance treatment) through Week 10. Thus, the drug 
will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction therapy), 
Day 1 of Week 6, Day 1 of Week 10. To maintain the study blind, patients of this arm will receive 
placebo (2 injections) on Day 1 of Week 4 and Week 8. After 10 weeks, patients will receive BCD-
085 once every 4 weeks starting from Week 14 through Week 50. If achieving ≥PASI 75 response 
at Week 52, patients will receive treatment with BCD-085 Q4W from Week 54 through Week 
154. 
In Arm 3 (control arm), patients will receive 2 subcutaneous injections of placebo (1.0 mL 
each) on Day 1 of Weeks 0, 1, 2, 4, 6, 8 and 10. Patients will receive BCD-085 120 mg once a 
week at Weeks 12, 13, 14, then Q4W starting from Week 18 through Week 50. If achieving ≥PASI 
75 response at Week 52, patients will receive treatment with BCD-085 Q4W from Week 54 
through Week 166. If failing to achieve ≥ PASI 75 response at Week 52, patients will discontinue 
the study. 
Patients will be followed up for 4 weeks after the last injection of the investigational 
product. 
Injections can be given to the abdomen, hips, or upper arms. Injections should be given at 
least 5 cm apart. 
During the entire study, patients are not allowed to use phototherapy, systemic therapy or 
live vaccines. 
Patients may use topical glucocorticoids (of mild to moderate potency) on the face, 
underarm, and genitals Patients may also use topical moisturizers, emollients, oils, and salicylic 
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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 is to be defined by the attending physician. 
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 examination including: 
• Baseline clinical characteristics and medical history, 
• Physical examination, 
• Blood pressure and wrist pulse, 
• Electrocardiography, 
• Chest20 X-ray, 
• Complete blood count,  
• Blood chemistry, 
• hs-CRP, atherogenicity index, apoB1/apoA1, 
• Glycated hemoglobin HbA1C (only for patients with confirmed diabetes mellitus), 
• Pregnancy test21, 
• Assessment of the patient’s infection status [Diaskintest® or blood testing for TB 
(QuantiFERON or T-spot)]; examination by the TB Specialist (required if the 
Diaskintest®/QuantiFERON/T-spot test results are uncertain), anti-HIV antibodies and p24 
antigen [HIVAg/Ab Combo], HBs-antigen, anti-HBcor antibodies [IgG + IgM/ IgM], and 
anti-HCV antibodies, qualitative PCR for HCV RNA/HBV DNA (only if the patient tests 
positive for respective antibodies), consultation with the Infectious Disease Specialist 
(required only if the patient tests positive for anti-HBcor or anti-HCV antibodies), 
microprecipitation reaction, and a direct hemagglutination assay (T. pallidum), 
• Beck’s depression inventory, 
                                                          
20 Chest X-ray is performed according to the standards of the study site. 
21 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• Psoriasis area and severity (PASI), including body surface area affected by psoriasis 
(BSA), assessment of the nail psoriasis using NAPSI, 
• Static Physicians Global Assessment (sPGA), 
• Assessment of psoriatic arthritis (the 66/68 swollen/tender joint count), functional activity 
(HAQ-DI), disease activity (assessed by the physician and by the patient, VAS), patient 
assessment of pain (VAS), and markers of inflammation (C-reactive protein and ESR), 
• Itch severity (VAS), 
• DLQI questionnaire. 
To measure the efficacy of treatment in the timeframes specified by the Protocol, changes 
over time in the PASI, NAPSI, and sPGA scores, VAS scores for itch severity, assessment of 
psoriatic arthritis (ACR 20/50/70), and quality of life (DLQI score) will be evaluated. 
 
 
 
For safety evaluation, the following will be closely monitored: all general disorders 
(including fever and flu-like syndrome), abnormal vital signs (blood pressure and wrist pulse), 
infectious complications, abnormal laboratory values (CBC results: hemoglobin, erythrocytes, 
platelets, leukocytes including changes in the leukocyte differential, ESR; blood chemistry: 
glucose, total bilirubin, ALT, AST, total protein, creatinine; urinalysis), assessment of 
cardiovascular risks (hs-CRP, atherogenicity index, apoB1/apoA1 ratio), cardiac disorders (ECG), 
lung disorders (chest X-ray). In some cases, to rule out tuberculosis or neoplasms that emerged 
during the study treatment, chest computed tomography can be done at the discretion of the TB 
Specialist. 
For immunogenicity assessment, blood samples will be drawn from the patients and 
analyzed for binding and neutralizing anti-BCD-085 antibodies. 
 
 
 
  
 
 
 


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4.3. Measures to minimize/eliminate bias 
4.3.1. Distribution of patients by study sites 
Patients’ recruitment at the study sites will be performed on a competitive basis. 
Recruitment can be re-opened if the Sponsor’s audit reveals patients who do not meet the eligibility 
criteria or patients with major Protocol violations (with no explanation timely provided to the 
Sponsor). 
4.3.2. Procedure of assigning study IDs 
Patients will be randomized, stratified, and assigned IDs according to the internal 
guidelines of JSC BIOCAD. 
Each study site will be assigned a 2-digit identification number. For example, the first site 
receives ID 01, the second – 02, the third – 03 etc. 
After signing the informed consent form, each patient receives a 5-digit screening ID 
consisting of a 2-digit site ID and a 3-digit subject’s ID (continuing numbering in sequence, as 
patients are enrolled at this site). This information is recorded in the source documents and 
screening log. For example, in the study site 02, the first patient who has signed the informed 
consent form will receive the screening ID 02-001.  
When all screening procedures are completed, and the investigator decides that the patient 
meets all the eligibility criteria, the investigator fills out a screening form and/or an eCRF and 
sends it to the BIOCAD’s clinical study project manager via e-mail or fax: +7 (495) 992 82 98 
(ext. 116). If JSC BIOCAD confirms the inclusion of this patient, a BIOCAD’s representative 
stratifies and randomizes the patient, assigns him/her a Subject ID, and e-mails a Randomization 
Form (with the Subject ID and the drug lot number to be used in this patient) to the investigator. 
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A representative of JSC BIOCAD will monitor the total number of enrolled patients. It is 
assumed that many patients would fail the screening since the eligibility criteria are rather strict. 
Therefore, the number of screened patients can be increased depending on the percentage of 
screening failures. 
4.3.5. Blinding and subject-specific lots of investigational products 
In the first, blinded, period of the study (until Week 12), neither investigators nor patients 
will know whether the active drug (BCD-085) or placebo is used.  
The investigator (the principal investigator, a member of the study team responsible for the 
treatment of this patient) will receive BCD-085/placebo in identical secondary packaging 
(cartons). Each product will have an individual lot number. Each lot number is patient-specific. 
Once the patient is enrolled in the study (randomized), the Sponsor will send to the 
investigator the Subject ID and appropriate lot number of the drug to be given to this patient. If 
the electronic randomization system is used, all numbers are generated automatically after the 
investigator enters all the required information. The investigator records the lot numbers in the 
source documents and the eCRF.  
Starting from Week 12 treatment arms will be unblinded. The investigators and patients 
will be made aware of the drug and the dose used. There will be no individual lots during this 
study stage. Batch number should be recorded. Unblinding will be performed at Visit 8 (Week 12) 
by opening the randomization envelops provided by the Sponsor with the investigational products.  
4.4. Description of the study treatment, doses, and dosing regimen of the investigational 
products. Description of the dosage form, packaging, and labeling of the investigational 
products 
4.4.1. Description of the study treatment, doses, and dosing regimen of the investigational 
products 
Patients in Arm 1 will receive BCD-085 120 mg given as two SC injections on Day 1 of 
Week 0, Week 1, Week 2, Week 4, Week 6, Week 8, Week 10 (blinded treatment period), then on 
Day 1 of Weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, 50. If achieving ≥PASI 75 response at Week 
52, patients will continue to receive BCD-085 120 mg once every 4 weeks starting from Week 54 


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(with injections given at Weeks 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 
118, 122, 126, 130, 134, 138, 142, 146, 150, 154). 
In Arm 2, patients will receive BCD-085 120 mg as two SC injections on Day 1 of Weeks 
0, 1, 2, 6, 10 (blinded treatment period). To maintain the study blind, patients of this arm will 
receive placebo (2 injections) on Day 1 of Week 4 and Week 8. At Week 12, treatment will be 
unblinded, and since then patients will continue to receive BCD-085 120 mg once every 4 weeks 
starting from Week 14. Thus, injections will be given at Weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, 
and 50. If achieving ≥PASI 75 response at Week 52, patients will continue to receive BCD-085 
120 mg once every 4 weeks starting from Week 54 with injections given at Weeks 54, 58, 62, 66, 
70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 
154. 
Patients in Arm 3 will receive placebo as two 1.0 mL SC injections on Day 1 of Week 0, 
Week 1, Week 2, Week 4, then on Day 1 of Week 6, Week 8, Week 10 inclusive (blinded treatment 
period). After that, they will be switched to BCD-085 120 mg SC with injections given on Day 1 
of Weeks 12, 13, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50. If achieving ≥PASI 75 response at 
Week 52, patients will continue to receive BCD-085 120 mg once every 4 weeks starting from 
Week 54 with injections given at Weeks 54, 58, 62, 66, 70, 74, 78, 82, 86, 90, 94, 98, 102, 106, 
110, 114, 118, 122, 126, 130, 134, 138, 142, 146, 150, 154, 158, 162, 166.  
The patients will be followed up until Week 158 (in Arms 1 and 2) or Week 170 (in Arm 3). 
Regardless of the arm where the patient is assigned to, during the main study period (Week 
0 through Week 54) SC injections will be performed by an authorized member of the study team 
at the study site (except for the injection on Week 54).  
At Week 54 patients will be trained on how to self-inject the investigational product. If 
necessary, the training can be repeated at any of the subsequent visits. 
During the extension study period (Week 54 to Week 154 for patients from Arms 1 and 2, 
Week 54 to Week 166 for patients from Arm 3), patients will self-inject the investigational product 
at home (on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 138, 142, 
150 in Arms 1 and 2; on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 
138, 142, 150, 158, 162 in Arm 3) after relevant training at the study site at Week 54. Injections 
of the investigational product on visit dates will be performed by an authorized member of the 
study team at Weeks 62, 74, 86, 98, 110, 122, 134, 146, 154 (in Arms 1 and 2) or at Weeks 62, 74, 
86, 98, 110, 122, 134, 146, 154, 166 (in Arm 3). The first self-injection of the investigational 


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product at Week 54 will be performed under the supervision of an authorized member of the study 
team. 
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. Description of the dosage form, packaging, and labeling of the investigational products 
See section 1.2. Name and description of investigational products. 
4.4.2.1. Test drug 
See Section 1.2.1. Test drug 
See Section 1.2.2. Placebo 
4.4.2.3. Labeling of investigational products 
See Section 1.2.3.  
4.5. Expected duration of the study and subjects’ participation in the study 
 The expected duration of the study is 65 months, which includes patients’ recruitment (up 
to 12 months), treatment period, follow-up period, and data collection and statistical processing. 
The expected duration of each subject’s participation in the study, including the screening period, 
active study phase and follow-up period, is about 162 weeks (for patients from Arms 1 and 2) or 
174 weeks (for patients from Arm 3). 
4.6. Description of the sequence and duration of all study periods 
4.6.1 Study visits and procedures 
The study includes the following periods: 
1. Screening (up to 28 days from signing the Patient Information Sheet with the Informed 
Consent Form, inclusive); 
2. Main treatment period (from Week 0 through Week 54;  
3. Extension treatment period (from Week 54 through Week 154 in Arms 1 and 2, from Week 
54 through Week 166 in Arm 3); 


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4. Follow-up period (from Week 154 through Week 158 in Arms 1 and 2, from Week 166 
through Week 170 in Arm 3). 
The Investigator will decide whether it is feasible and possible to include the patient in the 
extension study period based on efficacy data (PASI 75), tolerability and safety of BCD-085 in 
each particular patient during the main study period if the patient gives his/her consent to 
participate in the extension study period. If by the date of approval of Protocol BCD-085-7 version 
2.0 of 02-Nov-2018 the patient has completed all visits of the main treatment period, and the last 
injection of the investigational product at Week 50 was not more than 6 weeks ago, the Investigator 
should inform the patient about this Amendment and about an opportunity to continue the therapy 
in the extension study period, and invite the patient to come to the study site for reading and signing 
the new version of the Informed Consent Form (v. 2.0 as of 02-Nov-2018). If the patient 
agrees/refuses to visit the study site and/or is lost to follow-up, the investigator should record this 
in source documentation. If by the date when Protocol BCD-085-7 v. 2.0 of 02-Nov-2018 is 
approved the patient has not completed the main study period, the Investigator should inform the 
patient about this Protocol Amendment and an opportunity to participate in the extension study 
period, and the patient will sign the informed consent form during the planned visit. This should 
be recorded in the source documentation. 
Table 25 lists all the procedures to be performed in the study. All data obtained during 
these assessments must be confirmed by the source documents.  
The screening/baseline assessment should be performed within 28 days before the 
estimated date of the first infusion of the investigational product. Visit 1 should be within 4 days 
after the randomization date. Prior results may be used for certain screening tests and exams (see 
section 4.7 for details). CBC, blood chemistry, urinalysis, QuantiFERON (or T-Spot) can be 
repeated once at screening. Repeated collection of biospecimens is also allowed if the sample is 
lost, 
if 
any 
technical 
problems 
occur 
at 
the 
pre-analytical 
phase 
(defective 
sampling/storage/transportation of the material), or is the biospecimen is not suitable for analysis 
(e.g. due to hemolysis or milky serum). At the end of the screening period, the patient should be 
assessed for the inclusion/exclusion criteria and undergo randomization. The schedule of visits 
during the extension period is presented in Table 24. 


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Table 24. Schedule of visits during the extension period. 
Arms 1 and 2: patients initially randomized to BCD-085 arms, 
Arm 3: patients initially randomized to the placebo arm 
Visit 
Group 1 
Group 2 
Arm 3 
Visit 23 (Day 1 of Week 62) 
+ 
+ 
+ 
Visit 23-1 (Day 1 of Week 64) 
Not performed 
Not performed 
+ 
Visit 24 (Day 1 of Week 74) 
+ 
+ 
+ 
Visit 25 (Day 1 of Week 86) 
+ 
+ 
+ 
Visit 26 (Day 1 of Week 98) 
+ 
+ 
+ 
Visit 27 (Day 1 of Week 110) 
+ 
+ 
+ 
Visit 28 (Day 1 of Week 122) 
+ 
+ 
+ 
Visit 29 (Day 1 of Week 134) 
+ 
+ 
+ 
Visit 30 (Day 1 of Week 146) 
+ 
+ 
+ 
Visit 31 (Day 1 of Week 154) 
+ 
+ 
+ 
Visit 32 (Day 1 of Week 158) 
+ 
+ 
N/A 
Visit 32-1 (Day 1 of Week 166) 
Not performed 
Not performed 
+ 
Visit 32-2 (Day 1 of Week 170) 
Not performed 
Not performed 
+ 
 




































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Information for the Investigator about allowed changes in scheduled dates of visits 
The first visit can be conducted on any day of the week. However, all the subsequent visits 
must be conducted on the same day of the week, with the intervals specified by the visit schedule. 
Thus, if Visit 1 (“Day 1 of Week 0”) was conducted on Wednesday, all subsequent visits, starting 
from Visit 2 (“Day 1 of Week 1”), must also be conducted on Wednesdays.  
The table below contains information about the allowed changes in the dates of the study 
visits. 
Table 28. Allowed changes in the study visits during the main study period (Weeks 0 to 54). 
Visit name 
Allowed changes 
Note 
Screening 
N/A 
N/A 
Visit 1  
(Day 1 of Week 0) 
Not later than 4 days after 
randomization 
- 
Visit 2  
(Day 1 of Week 1) 
• 
Due to force-majeure 
circumstances: not later than 
in 7 days (inclusive) and not 
earlier than 3 days before the 
scheduled date 
• 
Due to AE: not later than in 14 
days (inclusive) 
 
 
• 
If a visit when an injection of the 
investigational product is scheduled 
has to be postponed by more than 3 
days, all subsequent visits must be re-
scheduled 
accordingly. 
The 
first 
postponement day is the day after the 
visit date. 
• 
If the patient misses this visit, 
subsequent visits are not re-scheduled. 
• 
Other cases of visit re-scheduling must 
be agreed with the Sponsor. 
• 
A severe violation of visit time 
windows from Week 0 to Week 52 is a 
postponement of a visit by more than 7 
days (inclusive) due to any reasons or 
by more than 14 days (inclusive) due to 
AEs.  
• 
All cases when visits have to be 
postponed by more than 7 days 
(inclusive) due to reasons not related to 
AEs or by more than 14 days 
(inclusive) due to AEs must be agreed 
with the Sponsor.  
 
Visit 3 
(Day 1 of Week 2) 
Visit 4  
(Day 1 of Week 4) 
Visit 5  
(Day 1 of Week 6) 
Visit 6  
(Day 1 of Week 8) 
Visit 7  
(Day 1 of Week 10) 
Visit 8 
(Day 1 of Week 12) 
Visit 8-148 
(Day 1 of Week 12) 
Visit 9  
(Day 1 of Week 14) 
Visit 10  
(Day 1 of Week 16) 
Visit 11  
(Day 1 of Week 18) 
Visit 12 
(Day 1 of Week 22) 
Visit 13 
(Day 1 of Week 24) 
Visit 14 
(Day 1 of Week 26) 
Visit 15 
(Day 1 of Week 30) 
Visit 16 
(Day 1 of Week 34) 
Visit 17 
(Day 1 of Week 38) 
                                                          
48 This visit is performed only for Arm 3. 


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Visit name 
Allowed changes 
Note 
Visit 18 
(Day 1 of Week 42) 
Visit 19 
(Day 1 of Week 46) 
Visit 20 
(Day 1 of Week 50) 
Visit 21 
(Day 1 of Week 52) 
Visit 22 
(Day 1 of Week 54) 
• The visit can be postponed by up to 
21 days (due to any reasons) 
• 
All cases when the visit has to be 
postponed by more than 21 days 
(inclusive) due to AEs must be agreed 
with the Sponsor.  
 
 
Table 29. Allowed changes in the study visits during the extension and follow-up periods 
(Weeks 55 to 170). 
Visit name 
Allowed changes 
Note 
Visit 23 (Day 1 of 
Week 62) 
• 
Due to force-majeure 
circumstances: not later than 
in 7 days (inclusive) and not 
earlier than 3 days before the 
scheduled date 
• 
Due to AE: not later than in 14 
days (inclusive) 
 
• 
If the date of a visit with the 
investigational product administration 
has to be shifted by more than 3 days, 
dates of the subsequent injections also 
should be shifted. 
• 
If the patient misses this visit, 
subsequent visits are not re-scheduled. 
• 
Other cases of visit re-scheduling must 
be agreed with the Sponsor. 
See 
Section 
6.3.1. 
“Treatment 
compliance” 
 
Visit 23-149 
(Day 1 of Week 64) 
Visit 24 (Day 1 of 
Week 74) 
• 
Due to force-majeure 
circumstances: not later than 
in 14 days (inclusive) and not 
earlier 3 days before the 
scheduled date 
 
• 
If the date of a visit with the 
investigational product administration 
has to be shifted by more than 3 days, 
dates of the subsequent injections also 
should be shifted. 
• 
If the patient misses this visit, 
subsequent visits are not re-scheduled.  
• 
Other cases of visit re-scheduling must 
be agreed with the Sponsor. 
See Section 6.3.1. “Treatment compliance” 
 
Visit 25 (Day 1 of 
Week 86) 
Visit 26 (Day 1 of 
Week 98) 
Visit 27 (Day 1 of 
Week 110) 
Visit 28 (Day 1 of 
Week 122) 
Visit 29 (Day 1 of 
Week 134) 
Visit 30 (Day 1 of 
Week 146) 
Visit 31 (Day 1 of 
Week 154) 
                                                          
49 Visits 23-1, 32-1, 32-2 are performed only in patients from Arm 3. 


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Visit name 
Allowed changes 
Note 
Visit 3250 (Day 1 of 
Week 158) 
Visit 32-151 (Day 1 
of Week 166) 
Visit 32-251 (Day 1 
of Week 170) 
 
4.6.2. Procedures by visits 
Procedures of Screening Period 
The screening period starts when the patient signs the informed consent form and lasts for 
not more than 28 days (Days -28 to 0) until the day when the patient is enrolled in the study. 
• Taking informed consent from the patient. 
• Taking medical history and documenting any patient complaints. 
• Collecting information about concomitant therapy (including therapies used within 
1 month before signing the ICF). 
• Blood pressure, wrist pulse, and body temperature. 
• Physical examination (including body weight and height). 
• Complete blood count52 
 
• Bloodchemistry36 
 
• Determination of hs-CRP (highly-sensitive C-reactive protein), atherogenicity 
index, apoB1/apoA1 ratio 
 
• Glycated hemoglobin HbA1c is measured only in patients with confirmed diabetes 
mellitus 
 
• Tests for HIV, HCV, HBV, and syphilis 
 
• Urinalysis36. 
• ECG. 
                                                          
50 Visit 32 is performed only in patients from Arms 1 and 2. 
51 Visits 32-1, 32-2 are performed only in patients from Arm 3. 
52At screening, the test can be repeated once, if the first result does not meet the eligibility criteria. 


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• Chest X-ray53. 
• Pregnancy test54. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• The patient fills out the Beck depression inventory. 
• For patients with psoriatic arthritis: swollen/tender joint count55 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• TB test56 
 
 
 
• Checking for eligibility (inclusion/non-inclusion criteria). 
• Inclusion in the study (randomization and stratification). 
• Recording SAEs. 
 
 
 
 
                                                          
53 Chest fluorography can be used instead of chest X-ray. Screening chest X-ray is not required if the patient had chest 
X-ray/fluorography/CT/MRI done within 3 months before signing the informed consent form for this study. 
54 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 
55 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
56 TB diagnostics can be performed with the skin test (Diaskintest) or blood test (QuantiFERON/T-spot). 
QuantiFERON/T-spot can be repeated once. Upon reconciliation with the Sponsor, the patient with uncertain 
Diaskintest/QuantiFERON/T-spot results can be enrolled in the study if the TB Specialist confirms in written that the 
patient has no TB infection, and the patient shows no signs of active TB according to the chest X-ray performed any 
time within 3 months before signing the ICF or during the screening. The Diaskintest results are valid if the test was 
performed within 3 months before signing the ICF. 


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Procedures of Visit 1 (Day 1 of Week 0) 
• Physical examination. 
• Blood sampling for immunogenicity study (must be done BEFORE the injection of 
BCD-085/placebo) 
 
• Complete blood count 
 
• Blood chemistry 
 
• Information about concomitant therapy. 
• Administration of BCD-085/placebo. 
• Blood pressure, wrist pulse, and body temperature are measured any time before 
and immediately after the administration of the investigational product. 
• Assessing injection site reactions (two times): 4 h and 8 h after the injection of 
BCD-085/placebo. 
• Recording AEs/SAEs. 
 
Procedures of Visit 2 (Day 1 of Week 1), performed 7 days after the first injection of BCD-
085/placebo 
• Physical examination. 
• The patient fills out the VAS for itch. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 3 (Day 1 of Week 2) 
• Physical examination. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 


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• Recording AEs/SAEs. 
Procedures of Visit 4 (Day 1 of Week 4) 
• Physical examination. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 5 (Day 1 of Week 6) 
• Physical examination. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 6 (Day 1 of Week 8) 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
 
 
• DLQI questionnaire. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Complete blood count 
 
• Blood chemistry 
 
• Urinalysis. 
• Information about concomitant therapy. 
• Assessing injection site reactions. 


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• Recording AEs/SAEs. 
 
 
Procedures of Visit 7 (Day 1 of Week 10) 
• Physical examination. 
• Administration of BCD-085/placebo. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 8 (Day 1 of Week 12) 
• Information about concomitant therapy. 
• Physical examination.  
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Nail Psoriasis Severity Index (NAPSI). 
• Assessment of psoriatic arthritis: swollen/tender joint count(66/68), VAS by the 
patient (pain, disease activity) and by the physician (disease activity), functional 
activity with HAQ-DI. 
• Unblinding. 
• Taking a blood sample for immunogenicity assay 
 
• Complete blood count
 
• Blood chemistry 
 
• hs-CRP, atherogenicity index, apoB1/apoA1 
 
• Urinalysis. 


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• Administration of BCD-085 (only to patients from Arm 3: first administration of 
BCD-085). 
• Blood pressure, heart rate and body temperature (immediately after dosing).57 
• ECG. 
• Assessing injection site reactions.58 
• Recording AEs/SAEs. 
 
Procedures of Visit 8-1 (Day 1 of Week 13) (only in patients from Arm 3) 
• Physical examination. 
• Information about concomitant therapy. 
• Second administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 9 (Day 1 of Week 14) 
• Physical examination. 
• Information about concomitant therapy. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 10 (Day 1 of Week 16) 
• Information about concomitant therapy. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
 
 
                                                          
57 For patients of Arm 3 just after the administration of the investigational product. 
58 In Arm 3, assessment of injection site reactions on Visit 8 (Week 12) is performed 4 h and 8 h after the injection of 
BCD-085. 


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• Recording AEs/SAEs. 
Procedures of Visit 11 (Day 1 of Week 18) 
• Physical examination. 
• Information about concomitant therapy. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 12 (Day 1 of Week 22) 
• Physical examination. 
• Information about concomitant therapy. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 13 (Day 1 of Week 24) 
• Information about concomitant therapy. 
• Taking a blood sample for immunogenicity assay 
 
• hs-CRP, atherogenicity index, apoB1/apoA1 
 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA).  
• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Complete blood count 
 
• Blood chemistry
 
• Urinalysis. 


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• Assessing psoriatic arthritis: swollen/tender joint count (66/68), VAS by the patient 
(pain, disease activity) and by the physician (disease activity), functional activity 
with HAQ-DI.  
• Recording AEs/SAEs. 
 
Procedures of Visit 14 (Day 1 of Week 26) 
• Physical examination (including body weight). 
• TB test59 
 
 
 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• ECG. 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
 
Procedures of Visit 15 (Day 1 of Week 30) 
• Physical examination. 
• Information about concomitant therapy. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
                                                          
59If the patient has to take a Diaskintest, he/she will receive a referral for the test on this Visit. The Diaskintest must 
be performed within 7 days after the referral. If the TB test show uncertain/positive results, the patient should be called 
to the study site for an unscheduled visit where he/she will be given a referral to a TB clinic. If the TB is confirmed, 
this must be registered as an AE, and the patient must be withdrawn from the study. Patients can continue the study if 
the TB Specialist provides a documented impression that the patient has no TB infection (the blood work for TB may 
be repeated on the discretion of the TB Specialist). 


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Procedures of Visit 16 (Day 1 of Week 34) 
• Complete blood count 
 
• Blood chemistry 
 
• Physical examination. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
 
Procedures of Visit 17 (Day 1 of Week 38) 
• Physical examination. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 18 (Day 1 of Week 42) 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
 
 
• DLQI questionnaire. 
• Complete blood count 
 
• Blood chemistry 
 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 


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• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Total blood volume drawn at the visit: 12.5 mL. 
Procedures of Visit 19 (Day 1 of Week 46) 
• Physical examination. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 20 (Day 1 of Week 50) 
• Physical examination. 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Information about concomitant therapy. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Procedures of Visit 21 (Day 1 of Week 52) 
• Information about concomitant therapy. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Nail Psoriasis Severity Index (NAPSI). 
• Assessing psoriatic arthritis: swollen/tender joint count (66/68), VAS by the patient 
(pain, disease activity) and by the physician (disease activity), functional activity 
with HAQ-DI. 


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• hs-CRP, atherogenicity index, apoB1/apoA1 
 
• Complete blood count 
 
• Recording AEs/SAEs. 
 
Procedures of Visit 22 (Day 1 of Week 54) 
• Assessing the patient for eligibility for the extension study period. 
• Physical examination (including body weight). 
• Taking a blood sample for immunogenicity assay 
. 
• Blood chemistry
. 
• Urinalysis. 
• Pregnancy test. 
• ECG. 
• TB test (skin test (Diaskintest) or blood test 
 
 
 
• The patient fills out Beck depression inventory. 
• Chest X-ray. 
• Blood pressure, wrist pulse, and body temperature.  
• Information about concomitant therapy. 
• Recording AEs/SAEs. 
If the patient continues to participate in the extension study period: 
• Training the patient on self-administration of the investigational product, fulfilling 
the Diary, requirements for investigational product transportation (in a cooling bag 
with cold packs) and storage, requirements for handling with used syringes and 
returning the syringes and the Diary. 
• Self-administration of BCD-085 (under the supervision of an authorized member 
of the study team). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Dispensing the Patient’s Diary.  


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Total blood volume drawn at the visit: 24 mL. 
Procedures of Visit 23 (Day 1 of Week 62) 
• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• For patients with psoriatic arthritis: swollen/tender joint count60 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP 
 
• Urinalysis. 
• Pregnancy test.61 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
                                                          
60 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
61 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 




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• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry
 
• Urinalysis. 
• Pregnancy test.63 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
 
Procedures of Visit 25 (Day 1 of Week 86) 
• Information about concomitant therapy. 
• Physical examination (including body weight). 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
                                                          
63 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• For patients with psoriatic arthritis: swollen/tender joint count64 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP, atherogenicity index, apoB1/apoA1 
 
• TB test (skin test (Diaskintest) or blood test
 
 
 
• Chest X-ray.65 
• Urinalysis. 
• Pregnancy test.66 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arms 1 and 2: 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 26 (Day 1 of Week 98) 
                                                          
64 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
65 Performed in patients with positive results of the skin test (Diaskintest) or blood test for TB (QuantiFERON or T-
spot). 
66 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• Urinalysis. 
• Pregnancy test.67 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arm 3: 
Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 27 (Day 1 of Week 110) 
• Information about concomitant therapy. 
• Physical examination. 
                                                          
67 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• For patients with psoriatic arthritis: swollen/tender joint count68 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP
 
• TB test 
 
 
 
• Urinalysis. 
• Pregnancy test.69 
• ECG. 
• Chest X-ray.70 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
                                                          
68 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
69 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 
70 Performed in patients with positive results of the skin test (Diaskintest) or blood test for TB (QuantiFERON or T-
spot). 


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• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arms 1 and 2: 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 28 (Day 1 of Week 122) 
• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA). 
• Nail Psoriasis Severity Index (NAPSI). 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• Urinalysis. 
• Pregnancy test.71 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arm 3: 
                                                          
71 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• For patients with psoriatic arthritis: swollen/tender joint count72 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• hs-CRP 
 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 29 (Day 1 of Week 134) 
• Information about concomitant therapy. 
• Physical examination (including body weight). 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• For patients with psoriatic arthritis: swollen/tender joint count73 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), function 
assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP, atherogenicity index, apoB1/apoA1 
 
                                                          
72 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
73 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 


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• TB test 
 
 
 
• Chest X-ray.74 
• Urinalysis. 
• Pregnancy test.75 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arms 1 and 2: 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 30 (Day 1 of Week 146) 
• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
                                                          
74 Performed in patients with positive results of the skin test (Diaskintest) or blood test for TB (QuantiFERON or T-
spot). 
75 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• Complete blood count 
 
• Blood chemistry 
 
• Urinalysis. 
• Pregnancy test.76 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Dispensing the investigational product for self-administration and a container for 
used syringes. 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arm 3: 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 31 (Day 1 of Week 154) 
• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
                                                          
76 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• For patients with psoriatic arthritis: swollen/tender joint count77 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), function 
assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP 
 
• Urinalysis. 
• Pregnancy test.78 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
Only for patients from Arm 3: 
• Dispensing BCD-085 to the patient. 
Only for patients from Arms 1 and 2: 
• Taking a blood sample for immunogenicity assay 
 
 
 
Procedures of Visit 32 (Day 1 of 158) The visit is performed only in patients from Arms 1 
and 2. 
• Information about concomitant therapy. 
• Blood pressure, wrist pulse, and body temperature (any time). 
• Physical examination (including body weight). 
• Complete blood count 
 
                                                          
77 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
78 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 


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• Blood chemistry 
 
• Atherogenicity index, apoB1/apoA1 
 
• TB test 
 
 
 
• Urinalysis. 
• Pregnancy test.79 
• ECG. 
• Chest X-ray. 80 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
 
Procedures of Visit 32-1 (Day 1 of Week 166) This visit is performed only for patients from 
Arm 3. 
• Information about concomitant therapy. 
• Physical examination. 
• Psoriasis Area and Severity Index (PASI), including Body Surface Area affected 
by psoriasis (BSA). 
• Static Physician’s Global Assessment (sPGA) 
• Nail Psoriasis Severity Index (NAPSI). 
 
 
• The patient fills out the VAS for itch. 
• DLQI questionnaire. 
                                                          
79 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 
80 Performed in patients with positive results of the skin test (Diaskintest) or blood test for TB (QuantiFERON or T-
spot). 


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• For patients with psoriatic arthritis: swollen/tender joint count81 (66/68), VAS filled 
out by the patient (pain, disease activity) and by the physician (disease activity), 
function assessment with HAQ-DI. 
• Checking the Patient’s Diary and withdrawing a detachable page. 
• Accounting of the investigational product. 
• Complete blood count 
 
• Blood chemistry 
 
• hs-CRP 
 
• Taking a blood sample for immunogenicity assay 
 
• Urinalysis. 
• Pregnancy test.82 
• Administration of BCD-085. 
• Blood pressure, heart rate and body temperature (immediately after dosing). 
• Assessing injection site reactions. 
• Recording AEs/SAEs. 
 
Procedures of Visit 32-2 (Day 1 of Week 170) This visit is performed only for patients from 
Arm 3. 
• Information about concomitant therapy. 
• Blood pressure, wrist pulse, and body temperature (any time). 
• Physical examination (including body weight). 
• Complete blood count 
 
• Blood chemistry 
 
• Atherogenicity index, apoB1/apoA1 
 
                                                          
81 Joints are assessed by the Assessing Physician (an Investigator who underwent training on assessing joints provided 
by the Sponsor). During the study, the patient’s joints will be assessed by one physician or, if absent, his/her 
representative. 
82 Pregnancy test detecting hCG in the urine (test strips). Pregnancy test is not required if the female patient is at least 
2 years post-menopausal or had a uterus or ovary surgery that makes pregnancy impossible. 






























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other chronic skin inflammatory disorders, immunodeficiency, concomitant conditions) with 
the onset/resolution dates (if applicable) 
− Medical history – main disease (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 within the 
last 6 months, 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 reason for discontinuation (if 
applicable). Medications for the treatment of psoriasis that the patient uses now or has been 
using within 6 months 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, Weeks 26, 54, 86, 134, 15896 and 17097) 
− Skin and mucosa (visual examination, describe all pathological changes that are not due to 
psoriasis) 
− Ear-nose-throat, respiratory system (examination, lung auscultation) 
− Cardiovascular system (heart auscultation, examination of major vessels area) 
− GI (examination, palpation of the abdominal area) 
− Palpation of the liver 
− Palpation of the spleen 
4.7.3. Vital signs 
Vital signs include axillary body temperature (°C), blood pressure (on one arm, mm Hg), 
and heart rate (wrist pulse, bpm). 
                                                          
96 Only for patients from Arms 1 and 2. 
97 Only for patients from Arm 3. 


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Blood pressure, pulse, and body temperature at Visit 1 (measured any time before and 
immediately after the injection of the investigational product).  
4.7.4. Laboratory tests 
Laboratory investigations include complete blood count, blood chemistry, hs-CRP, 
atherogenicity index and apoB1/apoA1, TB diagnostics with QuantiFERON/T-spot, blood 
sampling for immunogenicity testing, urinalysis. In addition, markers of HIV, hepatitis B and C, 
and syphilis will be determined at screening. 
The Protocol allows repeating the CBC and urinalysis once during the screening.  
Repeated collection of biospecimens is also allowed if the sample is lost, if any technical 
problems occur at the pre-analytical phase (defective sampling/storage/transportation of the 
material), or is the biospecimen is not suitable for analysis (e.g. due to hemolysis or milky serum). 
4.7.4.1. Complete blood count 
CBC is tested in accordance with the standard procedure. The test is performed at fasting 
(fasting means at least 8 hours after the last meal). This study includes the following CBC 
parameters: 
− Hemoglobin (g/L) 
− Erythrocytes (×1012/L) 
− Leukocytes (×109/L) 
− Platelets (×109/L) 
− Neutrophils (×109/L) 
− Lymphocytes (×109/L) 
− Monocytes (×109/L) 
− ESR (mm/h) by Westergren or capillary photometry 
 
Blood sampling is performed using standard procedures. 
 
 
 
 
 


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The specimens are shipped at +2 to +8 °C. 
4.7.4.2. Blood chemistry 
Blood chemistry is performed according to the standard procedure in 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),  
− ALT (U/L),  
− AST (U/L),  
− Total protein (g/L),  
− Creatinine (µmol/L) 
− Alkaline phosphatase (U/L), measured at screening only. 
. 
Blood sampling is performed using standard procedures. 
 
 
 
 
 
 
The specimens are shipped at +2 to +8 °C. 
4.7.4.3. Determination of hs-CRP, atherogenicity index, apoB1/apoA1 
To assess cardiovascular risks in study subjects, changes over time in highly-sensitive 
C-reactive protein, atherogenicity index and apoB1/apoA1 ratio will be determined. Concentration 
of highly-sensitive C-reactive protein will be used to assess psoriatic arthritis according to the 
ACR criteria. The investigations are performed at fasting state (12 hours without food, including 
sweet and alcohol beverages, do not smoke for 30 min before blood collecting) from one blood 
specimen. 
  


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The atherogenicity index is calculated using total cholesterol (tCs) and high-density 
lipoproteins (hd-LPP). The apoB1/apoA1 ratio is calculated using levels of apolipoproteins A1 
and B1. 
Concentration of hs-CRP is measured using latex-enhanced immunoturbidimetry. 
Concentration of total cholesterol is measured by CHOD/PAP assay. Concentration of HDL is 
measured also by CHOD/PAP assay but without sample precipitation. Concentration of 
apolipoproteins B1 and A1 is measured by immunoturbidimetry.  
 
 
 
 
 
 
4.7.4.4. Serological tests 
The test for HIV-infection detects antibodies to HIV-1, HIV-2, and p24 antigen (HIV 
Ag/Ab Combo) in the serum or plasma.  
The test for syphilis is performed as a microprecipitation (RPR-test) and direct 
hemagglutination assay. Other tests can also be used. If any of the tests shows positive results, 
other methods can be used to clarify the diagnosis. In this case, the actions must be reconciled with 
the Sponsor, and a consultation from a Dermatology/Venereology Specialist is required. The 
Dermatology/Venereology Specialist can request additional tests from the following list: specific 
tests for syphilis 
 
 
 
; non-specific tests for syphilis: 
 
 Other tests 
can also be used. 
The screening for HBV includes tests for HBsAg and total antibodies to HBcor antigen (anti-
HBcor total = IgG + IgM). If the test results for these markers (HBsAg and anti-HBcor total) are 
negative, the patient is considered eligible for the study by this criterion. If the patient tests positive 
for HBsAg, the patient cannot be included in the study regardless of the results for anti-HBcor. If 
the test results for HBsAg are negative but anti-HBcor total antibodies are detected, the patient 




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The tests are performed at screening. Test results for HIV, HCV, HBV, and syphilis 
obtained within 1 month before signing the ICF are valid at screening. 
4.7.4.5. Urinalysis 
Urine sampling and urinalysis will be performed using standard procedures. Urinalysis 
includes general properties of urine (color, clarity, specific gravity, pH, protein, glucose) and 
urinary sediment microscopy (epithelium, erythrocytes, leukocytes, cylinders, bacteria, salts). 
One urine re-testing can be performed during the screening. 
4.7.5. ECG 
12-lead ECG is recorded using a commonly used procedure. 
4.7.6. Tuberculosis diagnostics 
This study will accept results of the Diaskintest or QuantiFERON or T-spot assays obtained 
with standard procedures. Diaskintest/QuantiFERON/T-spot tests and their interpretations must 
be performed by a certified healthcare professional. 
Blood assay (QuantiFERON/T-Spot) can be performed the second time if the first one 
(QuantiFERON/T-Spot/Diaskintest) gives uncertain/positive results, or the results of the first test 
cannot be interpreted because the biomaterial was spoiled, pre-analytical step was violated, or 
expired kits were used. No letter from the Sponsor is required. 
Diagnostics of tuberculosis at screening 
QuantiFERON/T-spot can be repeated once at screening. Patients with uncertain 
Diaskintest/QuantiFERON/T-spot test are eligible for the study if a qualified specialist confirms 


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no TB infection (a written report must be provided) and the chest X-ray exam performed within 3 
months before signing the ICF reveals no signs of active TB infection. 
Diagnostics of tuberculosis at subsequent visits 
In sufficient time in advance before Visits 14, 22, 25, 27, 29, 32, and 32-2, on which the 
test is planned (if Diaskintest is planned for the patient), the patient will receive a referral to 
Diaskintest. Diaskintest results should be obtained not earlier than 14 days before Visits 14, 22, 
25, 27, 29, 32, and 32-2, respectively, where the test is to be performed. The Diaskintest must be 
performed within 7 days after the referral.  
During the main and extension periods (at Visits 14, 22, 25, 27, 29, 32, and 32-2), if the 
first test for TB (QuantiFERON/T-spot/Diaskintest) is uncertain/positive, blood for the second test 
for TB (QuantiFERON or T-spot) should be drawn as soon as possible. A written approval from 
the Sponsor is not required. All patients with initial uncertain/positive tests for TB should undergo 
chest X-ray; if necessary, X-ray can be replaced with or supplemented by chest computed 
tomography (if lesions suggesting tuberculosis have been detected in this area).  
If repeated tests (QuantiFERON/T-spot) give uncertain/positive results, the patient should 
be referred to a TB Specialist for a consultation. The TB Specialist should exclude or confirm the 
diagnosis of tuberculosis and decide whether the patient has contraindications to treatment with 
genetically engineered biological products (for diagnostics at Visits 14, 22, 25, 27, and 29).  
Results of additional diagnostics (repeated QuantiFERON/T-spot test) should be 
interpreted in the following way: 
If the test is negative, the patient can continue to participate in the study provided that chest 
X-ray shows no signs suggesting tuberculosis. 
If the test is uncertain, the patient can continue to participate in the study if the TB 
Specialist in his/her report states that the patient has no active tuberculosis and contraindications 
to genetically engineered biologic drugs. At the discretion of the TB Specialist, the patient can be 
administered with anti-TB agents (for prophylaxis). Information about these drugs should be 
recorded in the TB Specialist report, other source documents (medical case history, etc.) and eCRF. 
If the test is positive, the AE “positive test for tuberculosis” should be recorded. If the TB Specialist 
in his/her record states that the patient has active tuberculosis, the patient should be withdrawn 
from the study and referred to the TB Specialist for further treatment. If tuberculosis is confirmed, 
the AE’s name should be corrected to “confirmed tuberculosis” with localization of the lesion (if 


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this information is available). For diagnostics at Visits 14, 22, 25, 27, and 29: if the TB Specialist 
states that the patient with the positive TB test result has no active tuberculosis and 
contraindications to biologic drugs, the patient can be administered anti-TB agents for prophylaxis, 
and the Sponsor should approve via a letter the continuation of the study by this patient.  
 
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 Mycobacterium 
tuberculosis and Mycobacterium bovis, virulent strains of mycobacteria. The procedure and results 
assessment of Diaskintest® 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 occur. 
• 
Uncertain: hyperemia with no infiltrate. 
• 
Positive: an infiltrate (papula) of any size. 
The Diaskintest® is performed at a local TB clinic or at the study site if a qualified 
healthcare professional is available (materials for the tests performed at study sites will be provided 
by JSC BIOCAD). 
The Diaskintest results are valid if the test was performed within 3 months before signing 
the ICF. There is a high risk of false-negative results if the skin test if done more often than once 
in 3 months. 
4.7.6.2. Plasma test for gamma interferon (QuantiFERON test) 
The QuantiFERON test allows evaluating plasma levels of the specific gamma interferon to 
confirm or exclude the tuberculosis infection. 
 
 
 


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4.7.6.3. T-spot assay 
The T-spot is an immunobiological diagnostic test for tuberculosis. It is based on counting 
the T cells that have been specifically activated by Mycobacterium tuberculosis. This test is very 
much like QuantiFERON assay. However, blood is collected only to one tube.  
The patient must be fasting before providing a blood sample for the test. 
 
 
 
 
 
 
 
 
4.7.7. Chest x-ray 
Chest X-ray is performed with standard procedures of the study site to exclude pulmonary 
tuberculosis or other lung diseases. The scanning is performed according to the standards of the 


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study site or third-party contractors. If necessary, the Sponsor’s representative may request the 
images (if the subject develops active TB while in the study). 
Upon reconciliation with the Sponsor, chest fluorography at screening 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 3 months before signing the ICF. 
 At Visits 22 (Week 54), 25 (Week 86), 27 (Week 110), 29 (Week 134), 32 (Week 158) 
and 32-2 (Week 170), chest X-ray should be performed only in patients with positive/uncertain 
results of skin or cell tests for tuberculosis. If necessary, X-ray can be replaced with or 
supplemented by chest computed tomography (if lesions suggesting tuberculosis have been 
detected in this area).  
4.7.8. Assessment of the severity and area of psoriasis (PASI), including body surface area 
affected by psoriasis (BSA) 
The area and severity of skin signs of psoriasis can be assessed with PASI (Psoriasis Area 
and Severity Index). Changes in PASI during the study are assessed vs. values at baseline (for 
example, PASI 75 is a reduction of the PASI score by 75% vs. baseline). 
 
 
 
 
 


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Each symptom (erythema, infiltration, scaling) is assessed with a 4-score scale – from 0 
(none) to 4 (maximum), separately for skin of head and neck, body, upper and lower extremities 
(lines 1-3). Assessment is performed for the area most affected by the evaluated 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 
Infiltration 
 
 
 
 
 
Score 
0 
1 
2 
3 
4 
Scaling 
 
 
 
 
 
Score 
0 
1 
2 
3 
4 










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Each question is assessed with a 3-score system: very much – score 3, a lot – score 2, a 
little – score 1, not at all or not relevant – score 0. Question 7: the “Yes” answer scores 3; the “No” 
answer scores 0. If more than two questions are left unanswered, the questionnaire is considered 
invalid. The index is calculated as a sum of all scores: the minimum value is 0, the maximum – 
30. The higher the score is, the more quality of life is impaired. 
The survey must be filled in only by the patient or his/her legal representative. The DLQI 
survey must not be given to patients for completing at home. The patients should fill the 
questionnaire at the study site on the visit day. Completed questionnaires should be stored in the 
Investigator’s File. The total score is calculated automatically in the eCRF after the data are 
entered. 
4.7.11. Nail Psoriasis Severity Index (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 most affected nail is divided into quadrants. In each quadrant, the 
severity of the 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. 


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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 


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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 nail psoriasis must be assessed only in those patients who had it at screening. 
4.7.12. Patient assessment of itch 
The patient will assess the itch severity with a visual analog scale ranging from 0 (no itch) 
to 100 mm (unbearable itch).  
The investigator asks the patient to mark the scale (to cross the line that corresponds to 
the maximum severity of experienced itching). Then the physician measures the distance (mm) 
from the left end of the scale (0 mm) to the patient’s mark and records the result (mm). 
It is required that the patient fills the scale while at the study site during the visit. The 
completed VAS should be stored in the Investigator’s File. The score is to be recorded in the source 
documents. The Investigator records VAS results in the eCRF. A template of VAS is presented in 
Appendix 2. 
4.7.13. Assessment of psoriatic arthritis 
Psoriatic arthritis must be assessed only in those patients who had it at screening. 
The intensity of psoriatic arthritis will be assessed according to the American College of 
Rheumatology Criteria (ACR20/50/70). The response will be assessed by estimating the 66/68 
swollen/tender joint count, functional activity (HAQ-DI), disease activity (assessed by the 
physician and by the patient), patient assessment of pain (VAS), and markers of inflammation 
(CRP and ESR). 
The ACR20 response is recorded if the patient has a 20% decrease in tender/swollen joint 
counts (of 68/66, respectively) and a 20% improvement in 3 (or more) of 5 parameters: VAS score 
(pain assessed by the patient); VAS score (activity assessed by the patient); VAS (activity assessed 
by the Investigator); HAQ score; ESR or CRP. 
Joints are assessed by the Assessing Physician (an Investigator who underwent training on 
assessing joints provided by the Sponsor). During the study, the patient’s joints will be assessed 
by one physician or, if absent, his/her representative.  








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Results processing: 
The value of each category is calculated the following way: each item is scored from 0 to 
3 depending on the increase or decrease of the symptom severity. The total Beck Inventory score 
is from 0 to 62 (the lower the score the better the health state). 
Interpreting the Beck’s Depression Inventory 


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 Test results are interpreted as follows: 0-9 - no signs of depression; 10-15 - minimal 
depression (sub-depression); 16-19 - mild depression; 20-29 - moderate depression; 30-63 - severe 
depression. 
The test is performed by the patient at screening and Visit 22 (Week 54). 
Patients who scored 16 and more in the Beck’s Depression Inventory are not included in 
the study.  
4.7.15. Blood drawing for immunogenicity testing 
Immunogenicity will be assessed by detecting binding and neutralizing antibodies in 
patients’ serum. The test for binding antibodies to BCD-085 will be conducted at the Central 
Laboratory (JSC BIOCAD’s Separate Subdivision) with validated ELISA procedures. The assay 
for neutralizing antibodies to BCD-085 will be performed only if the test for binding antibodies 
shows positive results. The neutralizing Abs assay will be done at the Central Laboratory (JSC 
BIOCAD’s Separate Subdivision) with a validated ELISA protocol.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




















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compliance issues, or any other reasons. 
2. Local ethics committees or regulatory authorities decide to stop the study. 
4.8.2. Criteria for premature withdrawal of study subjects 
The patient will be withdrawn from the study in the following circumstances: 
1. Major violations of inclusion and/or exclusion criteria revealed after the enrollment 
(patients removed at the discretion of JSC BIOCAD)112. 
2. The patient withdraws his/her consent to participate in the study. 
3. The patient develops AEs or SAEs (including depressions), 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. During the main treatment period: The patient misses more than 2 injections (in this case, 
the patient’s removal must be approved by JSC BIOCAD, refer to section 6.3.1. Treatment 
compliance) or misses 2 consecutive visits or 3 visits in total, or the patient regularly (7 
times or more) violates the timing of the scheduled visits. 
5. During the extension treatment period (Week 54 to Week 154 for patients from Arms 1 and 
2, Week 54 to Week 166 for patients from Arm 3): if ≥ 20% injections are missed (≥ 5 
injections for patients initially randomized in Arms 1 or 2, ≥ 6 injections for patients 
initially randomized in Arm 3) or ≥ 2 consecutive visits/injections are missed; 
6. The patient gets pregnant. If pregnancy is suspected, the urine test for HCG must be 
performed. If the test gives a positive result, the patient must be withdrawn from the study 
(follow-up procedures are described in section 5.4). 
7. The patient is diagnosed with active tuberculosis during the treatment with the 
investigational product (the diagnosis should be confirmed by a documented impression 
from the TB Specialist); 
8. The study is terminated by the decision of JSC BIOCAD, local ethics committees or 
regulatory authorities. 
9. The patient uses medications prohibited by the Protocol. 
10. The patient dies. 
                                                          
112 Violation of eligibility criteria justified by the investigator and approved by the Sponsor is not a reason for removing 
the patient from the study. 


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The investigator must inform JSC BIOCAD within 24 h about the patient’s 
premature withdrawal and specify the reason. 
If the subject discontinues the study, an Early Withdrawal Form should be filled out in the 
CRF. The follow-up procedures for the discontinued subjects are described in section 5.4 
Procedures by Visits. 
Patients who discontinue the study will not be replaced. 
For further details see Section 11.6. 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.  
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. 
Drug accountability records must be available to the CRA during each monitoring visit. 
Accounting records should include: 
• Delivery confirmation; 
• Inventory at the study site; 
• Use of the investigational products 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 provided by JSC BIOCAD; Unused investigational product is not 
used for any other purpose except this study.  
The CRA from JSC BIOCAD will regularly inspect drug accountability records. 


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The patient will return used syringes in a special container and cardboard cartons 
(secondary packaging) at every visit. The investigator should check the amount of the 
investigational product used. 
4.9.1. Handling of the investigational products 
The investigational product will be delivered to the study site before the study start (before 
the inclusion of the first patient). All packs will have a “For clinical studies” label.  
At the study site, the investigational product must be stored at 2 to 8 °С, protected from 
light, in a limited access area. Access to the storage area will be granted only to the Principal 
Investigator, co-investigators, members of the study team, and an authorized representative of the 
site administration who has access to the storage area granted by the local regulations. The 
investigator must maintain a temperature log.  
The investigator must ensure safe storage of the investigational product to prevent loss, 
theft, or improper environmental conditions (temperature) specified by the Sponsor and described 
in the Investigator Brochure. 
During the extension period from Week 54, BCD-085 will be given to the patients so that 
they can self-inject it at home. The investigational product should be transported by the patients in 
a cooling bag with additional cold packs to keep the temperature mode. The investigators should 
inform the patients that after arriving at home they should place the investigational product in the 
refrigerator (not in the freezer) at 2 to 8 °C; the investigational product must not be frozen. 
Guidelines on transportation, storage and use of the investigational product are given in the 
Patient’s Diary. Patients should be informed that they have to return a container with used syringes 
and cardboard cartons of the secondary packaging back to the study site during each visit. If there 
is no injection scheduled, the patient should return unused syringes. The investigator should check 
the amount of the investigational product used (and not used, if applicable). 
4.10. Procedure for code keeping and unblinding 
As this study is double-blind, the test product and placebo will be identified only by the 
patient-specific lot number. JSC BIOCAD will prepare 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 site and 
stored in the Investigator’s File. 


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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. 
The 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. 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. In 
emergency cases, when urgent unblinding is required for the patient’s benefit, the Investigator can 
unblind the treatment code first and then inform the representative of the Sponsor. After 
completing all necessary procedures, the Investigator should fill out the unblinding form and send 
it to JSC BIOCAD (to the Study Monitor, Drug Safety Division or Medical Expert) within 24 h 
from the moment when the code was unblinded. After unblinding, the Investigator should record 
this in the source documents. 
At Week 12, the treatment will be unblinded by opening the randomization envelops. This 
should be recorded in the primary documentation.  
Each patient participating in the study will receive a Study Subject’s Card, which will 
contain the Protocol title and code, study site number, and contact data of the Investigator. 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 healthcare professional of 
another medical facility (other than the study center) can contact the Investigator to discuss 
benefits 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 to be recorded in the CRF should be present in the source documents of the study 
site. 
In this study, no data will be entered directly to the CRFs without prior entering to the 
source documents. 
5. ELIGIBILITY AND EXCLUSION OF STUDY SUBJECTS 


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5.1. Inclusion criteria 
1. Signed informed consent form (ICF). 
2. Age of at least 18 years old at the time of signing the ICF. 
3. Moderate to severe plaque psoriasis diagnosed at least 6 months before signing the ICF. 
4. Patients who received at least one course of phototherapy or 113 systemic therapy for psoriasis 
or are candidates114 for such treatment according to the investigator. 
5. Body surface area (BSA) affected by psoriasis of 10% or greater, the PASI score of 10 or 
greater, and the sPGA score of 3 or greater at screening. 
6. 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).  
7. The ability of the patient (in the Investigator’s opinion) to follow the Protocol procedures. 
8. Patients of both sexes and their partners with reproductive potential must implement reliable 
contraceptive methods starting from signing the ICF to 20 weeks after the last dose of the 
investigational product. This requirement does not apply to patients after surgical sterilization 
and to females who are post-menopausal for 2 years or longer. Reliable contraceptive methods 
include one barrier method in combination with one of the following: spermicides, intrauterine 
device/oral contraceptives. 
5.2. Exclusion criteria 
1. Baseline erythrodermic, pustular, or guttate psoriasis or any other skin disorders (e.g. eczema) 
that can affect/complicate the assessment of psoriasis treatment.  
2. Use of the following medications: 
• Prior exposure to any therapeutic monoclonal antibodies targeting IL-17 or its receptor; 
• Prior exposure to more than one drug containing monoclonal antibodies or their 
fragments; 
• Prior exposure to any monoclonal antibodies given within 12 weeks before signing the 
ICF; 
                                                          
113 Systemic therapy refers to any non-biologics (methotrexate, cyclosporine, acitretin, mycophenolate mofetil, 
apremilast, calcitriol derivatives, etc.), or genetically engineered biologics (TNF inhibitors, anti-cytokine drugs, 
anti-CD20 drugs, etc.). 
114 BCD-085 is planned to be used as either a first- or second-line treatment, so the study involves treatment-naive 
patients along with those who failed to respond to systemic therapy or phototherapy. 


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• Use of any systemic115 medications for the treatment of psoriasis (including 
glucocorticoids, methotrexate, sulfasalazine, cyclosporine, acitretin, mycophenolate 
mofetil, apremilast, calcitriol derivatives, etc.) within 4 weeks before signing the ICF. If 
these drugs were stopped less than 4 weeks before signing the ICF, the screening period 
should be extended up to 8 weeks during which no new systemic drugs are allowed; 
• Use of phototherapy within 4 weeks before signing the ICF; 
• Use of topical116 medications for the treatment of psoriasis within 2 weeks before signing 
the ICF; 
• Vaccination with live or attenuated vaccines within 8 weeks before signing the ICF. 
3. Any active systemic infection or recurrent infection at screening/randomization. 
4. HIV, hepatitis B, hepatitis C, or syphilis117. 
5. Blood chemistry abnormalities appearing as:  
a) creatinine > 2 × upper limit of normal (ULN) at screening; 
b) ALT, AST or alkaline phosphatase > 2.5 × ULN at screening; 
с) bilirubin > 1.5 × ULN at screening; 
                                                          
115 Except for NSAIDs. 
116 Patients may use topical glucocorticoids (of mild to moderate potency) on the face, underarm, and genitals. Patients 
may also use topical moisturizers, emollients, oils, and salicylic acid ointments, topical antibacterial and/or 
antimycotic agents as needed. Patients should discontinue all local skin products (medications or cosmetics) 24 hours 
before the planned PASI assessment. 
117 The screening for HBV includes tests for HBsAg and total antibodies to HBcor antigen (anti-HBcor total = IgG + 
IgM). If the test results for these markers (HBsAg and anti-HBcor total) are negative, the patient is considered eligible 
for the study by this criterion. If the patient tests positive for HBsAg, the patient cannot be included in the study 
regardless of the results for anti-HBcor. If the test results for HBsAg are negative but anti-HBcor total antibodies are 
detected, the patient should undergo an additional examination. The additional examination should include the 
following: qualitative PCR for HBV DNA, anti-HBcor IgM, and a consultation with the Infectious Disease Specialist. 
The activity of liver transaminases and concentration of bilirubin in blood chemistry results should be also considered. 
Having considered the examinations and test results, the Sponsor will decide whether to approve such a patient for 
the study. If it is known that the patient had hepatitis B infection in the past, an additional examination may be 
performed along with the main examination (blood samples for HBsAg, anti-HBcor total, anti-HBcor-IgM and blood 
samples for qualitative PCR to HBV DNA are taken on the same day). 
The patient with anti-HCV antibodies can be included in the study if all of the following conditions are met: negative 
qualitative PCR results for HCV RNA (this test is performed only if anti-HCV antibodies are detected); no 
abnormalities (increased transaminases or bilirubin levels) found in blood chemistry; the Infectious Disease Specialist 
provides a documented conclusion that the patient has no HCV/cured HCV; and the Sponsor approves the enrollment 
of this patient. If it is known that the patient had HCV infection in the past, an additional examination may be 
performed along with the main examination (blood samples for anti-HCV and blood samples for qualitative PCR for 
HCV RNA are taken on the same day). 
The patient who has a positive test for syphilis can be included in the study at the discretion of the Sponsor if the 
Dermatology/Venereology Specialist provides a documented report that the patient has no syphilis/cured syphilis. An 
additional examination may be required to confirm the diagnosis (at the discretion of the Dermatology/Venereology 
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6. Leukocyte count < 3.0 × 109/L; absolute neutrophil count < 2.0 × 109/L; platelet count < 100 
× 109/L, or hemoglobin < 90 g/L according to complete blood count at screening. 
7. Any psychiatric conditions including severe depressive disorders and/or any history of suicidal 
thoughts or suicidal attempts118. 
8. Signs of clinically significant depression (Beck’s score ≥ 16 at screening). 
9. Alcohol or substance abuse. 
10. Tuberculosis now or in the past. 
11. Latent TB infection (positive results of the Diaskintest119, QuantiFERON test, or T-spot). 
12. Confirmed by source documentation and ongoing at screening, concurrent diseases that may 
increase the risk of adverse events during the study therapy or affect the evaluation of psoriasis 
symptoms (mask, enhance or alter the symptoms of psoriasis, or cause clinical or 
laboratory/instrumental symptoms similar to those of psoriasis): 
• Active inflammatory diseases or aggravation of chronic inflammatory diseases other than 
psoriasis; 
• Functional class III-IV stable angina of effort, unstable angina or a history of myocardial 
infarction within 1 year before signing the ICF; 
• Moderate to severe cardiac failure (NYHA class III-IV); 
• Treatment-resistant hypertension120;  
• Severe asthma, a history of angioedema; 
• Moderate to severe respiratory failure, grade 3/4 chronic obstructive pulmonary disease; 
• Diabetes mellitus with inadequate glycemic control, i.e. if HbA1C121 level is ≥ 8% (to be 
valid, results should be obtained at screening or within 3 months before signing the ICF); 
                                                          
118 This exclusion criterion can be confirmed or rejected on the basis of medical records or as told by the patient. 
Patient’s medical history that can, in the opinion of the investigator, jeopardize the patient or affect his/her ability to 
follow the protocol must be carefully evaluated. 
119 TB diagnostics can be performed with the skin test (Diaskintest) or blood test (QuantiFERON/T-spot). 
QuantiFERON/T-spot can be repeated once. Upon reconciliation with the Sponsor, the patient with uncertain 
Diaskintest/QuantiFERON/T-spot results can be enrolled in the study if the TB Specialist confirms in written that the 
patient has no TB infection, and the patient shows no signs of active TB according to the chest X-ray performed any 
time within 3 months before signing the ICF or during the screening. The Diaskintest results are valid if the test was 
performed within 3 months before signing the ICF. 
120 Treatment-resistant arterial hypertension is defined as blood pressure above the target range despite the concurrent 
use of a combination of three anti-hypertensive drugs of different classes, necessarily including a diuretic, and non-
medication methods (salt-free diet, controlled physical exercise). 
121 Glycated hemoglobin is measured only in patients with suspected/diagnosed diabetes mellitus. 


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•  Thyrotoxicosis persisting despite thyrostatic drugs or hypothyroidism not compensated 
with thyroid hormone drugs122;  
• Systemic autoimmune diseases (including but not limited to systemic lupus 
erythematosus, rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, 
non-specific ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed 
connective tissue disease123, overlap syndrome, etc.); 
• Any other underlying conditions (including but not limited to metabolism, hematology, 
renal, hepatic, pulmonary, neurological, endocrine, cardiac, and gastrointestinal 
disorders; infections) that, in the opinion of the Investigator, may affect the course of 
psoriasis, affect the assessment of its symptoms, or put the patient using the study therapy 
at unacceptable risk. 
13. Malignancies with less than 5 years of remission.  
14. Known severe allergies (anaphylaxis or drug allergy to two or more drugs). 
15. Known allergy or intolerance to monoclonal antibody drugs (murine, chimeric, humanized, or 
fully human) or any other components of the test drug or comparator. 
16. Major surgery within 30 days before the screening, or a major surgery being scheduled at any 
time during the study. 
17. Severe 
infections 
(including 
those 
that 
required 
hospitalization 
or 
parenteral 
antibacterial/antimycotic/antiprotozoal agents) within 6 months before signing the ICF. 
18. Use of systemic antibacterial/antimycotic/antiprotozoal agents within 2 months before signing 
the ICF. 
19. More than 4 episodes of respiratory infections within 6 months before signing the ICF. 
20. Episodes of systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, etc.) 
within 6 months before signing the ICF. 
21. History of epileptic attacks or seizures. 
22. Any concurrent diseases during which, in the Investigator’s opinion, the study therapy can 
harm the patient. 
23. Pregnancy, breastfeeding, or planning for pregnancy while participating in the study. 
                                                          
122 In case of a history of thyroid disorders with thyrotoxicosis or hypothyroidism, the patient can participate in the 
study if he/she has laboratory confirmation of euthyroidism within 3 months before signing the ICF, and no symptoms 
developing during therapy with stable doses of antithyroid drugs/thyroid hormones for at least 4 weeks before signing 
the ICF. 
123 Signs/symptoms of psoriatic arthritis are not considered an exclusion criterion. 


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24. Participation in any other clinical study within 3 months before signing the ICF or 
simultaneous participation in other clinical studies.  
25. Patients who have been already randomized in the study but then withdrawn due to any reasons 
cannot be included in the study. 
5.3. Withdrawal criteria 
The patient will be withdrawn from the study in the following circumstances: 
1. Major violations of inclusion and/or exclusion criteria revealed after the enrollment (patients 
removed at the discretion of JSC BIOCAD)124. 
2. The patient withdraws 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. During the main treatment period: The patient misses more than 2 injections (in this case, the 
patient’s removal must be approved by JSC BIOCAD, refer to section 6.3.1. Treatment 
compliance) or misses 2 consecutive visits or 3 visits in total, or the patient regularly (7 times 
or more) violates the timing of the scheduled visits. 
5. During the extension treatment period (Week 54 to Week 154 for patients from Arms 1 and 2, 
Week 54 to Week 166 for patients from Arm 3): If ≥ 20% injections are missed (≥ 5 injections 
for patients initially randomized in Arms 1 or 2, ≥ 6 injections for patients initially randomized 
in Arm 3) or ≥ 2 consecutive visits/injections are missed; 
6. The patient gets pregnant. If pregnancy is suspected, the urine test for HCG must be performed. 
If the test gives a positive result, the patient must be withdrawn from the study (follow-up 
procedures are described in section 5.4). 
7. The patient is diagnosed with active tuberculosis during the treatment with the investigational 
product (the diagnosis should be confirmed by a documented impression from the TB 
Specialist); 
8. The study is terminated by the decision of JSC BIOCAD, local ethics committees or regulatory 
authorities. 
9. The patient uses medications prohibited by the Protocol. 
                                                          
124 Violation of eligibility criteria justified by the investigator and approved by the Sponsor is not a reason for removing 
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10. The patient dies. 
The investigator must inform JSC BIOCAD within 24 h about the patient’s 
premature withdrawal and specify the reason. 
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 the investigational product 
The following should be done if the patient who received at least one dose of the 
investigational product discontinues the study early: 
- On the day of withdrawal, the Early Withdrawal Visit should be conducted and the 
investigator should complete the Early Withdrawal Visit and the End of Study forms in the eCRF. 
The Protocol does not specify the amount of procedures to be performed during the Early 
Withdrawal Visit; this is to be determined on a case-by-case basis.  
Said procedures are mandatory for all subjects who prematurely withdrew from the study, 
except for the subjects who are lost to follow-up or are physically unable to attend the visit. All 
records must be supported with appropriate source documents. 
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 is to be followed up until the AE or 
SAE resolves completely.  
If a woman involved in the clinical study or a partner of a clinical study participant becomes 
pregnant, this does not need to be reported as an AE unless the baby has any congenital abnormality 
or birth defect (these should be recorded as SAEs). However, all pregnancies must be documented 
in a Pregnancy Report Form and reported to the Sponsor as soon as possible. Women who 
discontinued the study because of becoming pregnant during the study should be monitored 
throughout the entire pregnancy and 6 months after childbirth to evaluate the mother’s and child’s 
health. Such monitoring is performed when possible and requires patient’s consent for the 
pregnancy follow-up. Information on pregnancy course and outcome should be recorded in the 
source documentation (with consent from the patient).  
Information about the health of the patient prematurely withdrawn from the study must be 
recorded in the source documentation and eCRF. 


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5.4.2. Follow-up of subjects who did not receive a single dose of the investigational product 
If the patient discontinues the study before getting the first dose of the investigational 
product, the investigator must fill out the End of Study Form in eCRF 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 discontinues the study before the first dose of the investigational product, 
his/her information will not be included in the safety analysis. 
 
 


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6. TREATMENT OF STUDY SUBJECTS 
6.1. Study therapy 
In Arm 1, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment) and then once every 2 weeks through Week 10 (inclusive). After 10 weeks, 
patients will receive BCD-085 once every 4 weeks starting from Week 14 through Week 50. If 
achieving ≥PASI 75 response at Week 52, patients will receive treatment with BCD-085 Q4W 
from Week 54 through Week 154.  
In Arm 2, the test drug BCD-085 will be used at a dose of 120 mg given as two 
subcutaneous injections according to the following schedule: once a week for the first 3 weeks 
(induction treatment) and then Q4W (maintenance treatment) through Week 10. Thus, the drug 
will be administered on Day 1 of Week 0, Day 1 of Week 1, Day 1 of Week 2 (induction therapy), 
Day 1 of Week 6, Day 1 of Week 10. To maintain the study blind, patients of this arm will receive 
placebo (2 injections) on Day 1 of Week 4 and Week 8. After 10 weeks, patients will receive 
BCD-085 once every 4 weeks starting from Week 14 through Week 50. If achieving ≥PASI 75 
response at Week 52, patients will receive treatment with BCD-085 Q4W from Week 54 through 
Week 154. 
In Arm 3 (control arm), patients will receive 2 subcutaneous injections of placebo (1.0 mL 
each) on Day 1 of Weeks 0, 1, 2, 4, 6, 8 and 10. Patients will receive BCD-085 120 mg once a 
week at Weeks 12, 13, 14, then Q4W starting from Week 18 through Week 50. If achieving ≥PASI 
75 response at Week 52, patients will receive treatment with BCD-085 Q4W from Week 54 
through Week 166. If failing to achieve ≥ PASI 75 response at Week 52, patients will discontinue 
the study. 
Patients will be followed up for 4 weeks after the last injection of the investigational 
product. 
Injections can be given to the abdomen, hips, or upper arms. Injections should be given at 
least 5 cm apart. 
Patients are not allowed to use phototherapy, systemic therapy (except for NSAIDs) or live 
vaccines while they are in the study. 
Patients may use topical glucocorticoids (of mild to moderate potency) on the face, 
underarm, and genitals Patients may also use topical moisturizers, emollients, oils, and salicylic 


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acid ointments, topical antibacterial and/or antimycotic agents as needed. Patients should 
discontinue all local skin products (medications or cosmetics) 24 hours before the planned PASI 
assessment. 
6.1.1. Preparation of the investigational products for administration and administration 
procedure 
6.1.1.1. Test drug and placebo 
Regardless of the arm where the patient is assigned to, during the main study period (Week 
0 through Week 54) SC injections will be performed by an authorized member of the study team 
at the study site (except for the injection on Week 54). 
At Week 54 patients will be trained on how to self-inject the investigational product. If 
necessary, the training can be repeated at any of the subsequent visits. 
During the extension study period (Week 54 to Week 154 for patients from Arms 1 and 2, 
Week 54 to Week 166 for patients from Arm 3), patients will self-inject the investigational product 
at home (on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 138, 142, 
150 in Arms 1 and 2; on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 
138, 142, 150, 158, 162 in Arm 3) after relevant training at the study site at Week 54. Injections 
of the investigational product on visit dates will be performed by an authorized member of the 
study team at Weeks 62, 74, 86, 98, 110, 122, 134, 146, 154 (in Arms 1 and 2) or at Weeks 62, 74, 
86, 98, 110, 122, 134, 146, 154, 166 (in Arm 3). The first self-injection of the investigational 
product at Week 54 will be performed under the supervision of an authorized member of the study 
team. 
At each visit from Week 54 to 146, patients will receive the investigational product for self-
administration in an amount sufficient until the next visit 
. 


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Injections can be given to the abdomen, hips, or upper arms. Injections should be given at 
least 5 cm apart. 
The investigational product should be transported by the patients in a cooling bag with 
additional cold packs to keep the temperature mode. The investigators should inform the patients 
that after arriving at home they should place the investigational product in the refrigerator (not in 
the freezer) at 2 to 8 °C; the investigational product must not be frozen. Guidelines on 
transportation, storage and use of the investigational product are given in the Informed Consent 
Form and the Patient’s Diary. Patients should be informed that they have to return a container with 
used syringes and cardboard cartons of the secondary packaging back to the study site during each 
visit. If there is no injection scheduled, the patient should return unused syringes. The investigator 
should check the amount of the investigational product used (and not used, if applicable). 
Procedure for subcutaneous injection: 
The subcutaneous injection procedure is presented in the Patient Information Sheet with 
the Informed Consent Form, as well as in the Patient’s Diary. 
 
 
  
 
 
 
 
 
 
 
 
 
 


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• 
  
 
 
 
 
  
 
 
Disposal of auxiliary materials 
Unused solution of the investigational product, used syringes, cotton swabs, and other 
auxiliary materials should be disposed of according to study site procedures. 
The secondary packages should be stored at the study site until the visit of the study CRA 
so they can be counted. After being counted, they can be disposed of. 
During the extension period, patients will self-inject the investigational product at home. 
They should place used syringes in a special container and return it at a closest scheduled visit. 
The patients should also return the secondary packaging of the investigational product (cartons) to 
the study site so that the Clinical Study Monitor can count them. 
6.1.2. Adjustment and discontinuation of study therapy 
6.1.2.1. Dose modification and discontinuation of the investigational product 
No dose modifications for the investigational product 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. 
6.1.2.1.1. Follow-up for toxicity 
In case of temporary or permanent treatment 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 
the investigational product. 


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6.1.3. Overdose 
6.1.3.1. Overdose with the test drug 
No overdose events have been described with BCD-085. The effects of BCD-085 injected 
at single doses higher than 3 mg/kg are not known.  
In this study, an overdose is defined the following way: administration of BCD-085 at a 
dose greater than 120 mg or shortening of the interval between two doses by more than 3 days. 
Shortening the between-visit periods by 3 days or less is not considered an overdose. 
If an overdose is registered in this study, and the patient develops some adverse symptoms 
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 may use topical glucocorticoids (of mild to moderate potency) on the face, 
underarm, and genitals. The patients may use topical moisturizers, emollients, oils, or salicylic 
acid ointments as needed. Patients should discontinue all local skin products (medications or 
cosmetics) 24 hours before the planned PASI assessment. 
The patients can use single doses of systemic glucocorticoids to manage acute anaphylactic 
reactions, shock, or other life-threatening events that have developed as adverse events during the 
study. 
The patients can use non-steroidal anti-inflammatory drugs (NSAIDs) and medications for 
the treatment of other disorders (except for psoriatic arthritis). 
6.2.2. Prohibited concomitant therapy 
Methods and medications prohibited in this study: 
 Biologics (including other anti-IL-17 monoclonal antibodies, TNFα inhibitors, anti-
cytokine agents, etc.); 


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 Systemic medications for psoriasis/psoriatic arthritis, including hydroxyurea, acitretin, 
cyclosporine, methotrexate, apremilast, fumaric acid derivatives and dimethyl 
fumarate, intracellular kinase inhibitors, etc., except for NSAIDs; 
 Systemic and intra-articular glucocorticoids; 
 Phototherapy [including selective phototherapy (UVB) and photochemotherapy 
(PUVA)], 
 Any unauthorized products other than BCD-085; 
 Opioid analgesics; 
 Vaccination with live vaccines. 
The study participant who has 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. 
6.3.1. Treatment compliance 
Criteria of treatment non-compliance during the period from Week 0 to Week 52 (the 
patient must be withdrawn from the study if meeting any of them): 
- The patient misses more than 2 injections of the investigational product (removal should 
be reconciled with JSC BIOCAD), or 
- The patient misses 2 consecutive visits or a total of 3 visits in the study, or 
- The patient regularly violates the visit schedule (> 7 violations). 
Starting from Visit 2, visits can be postponed by up to 14 days (inclusive) due to AEs or 
by up to 7 days (inclusive) due to other reasons (for all patients; if the date of a visit with 
BCD-085/placebo administration has to be shifted by more than 3 days, dates of the subsequent 
injections also should be shifted. The first postponement day is the day after the visit date). Other 
cases of visit re-scheduling must be agreed with the Sponsor. 
A severe violation of visit time windows from Week 0 to Week 52 is a postponement of a 
visit by more than 7 days (due to any reasons) and by more than 14 days (due to AEs). All cases 


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when visits have to be postponed by more than 7 days (due to any reasons) or by more than 14 
days (due to adverse events) must be agreed with the Sponsor. In case of more than 7 severe 
violations of visit time windows, the patient is considered non-compliant and is withdrawn from 
the study. 
Compliance criteria for the extension and follow-up periods (Week 54 to Week 170) 
• 
The patient who misses 20% or more injections of the investigational product during the 
extension study period (5 or more injections for patients initially randomized to Arms 1 and 
2; 6 or more injections for patients initially randomized to Arm 3) or misses 2 or more 
consecutive visits/injections will be withdrawn from the study. 
• 
Visit 22 can be postponed by up to 21 days (inclusive) due to any reasons. If the visit has to 
be postponed by more than 3 days, dates of subsequent visits should be shifted accordingly. 
• 
Visits 23 and 23-1 can be postponed by 7 days (inclusive) due to reasons not related to safety 
and by up to 14 days (inclusive) due to safety reasons. If the date of a visit with the 
investigational product administration has to be shifted by more than 3 days, dates of the 
subsequent injections also should be shifted. 
• 
A self-injection of the investigational product can be postponed by not more than 3 days. The 
patient should record the actual injection date and specify the reason for the postponement. 
• 
Starting from Visit 24, not more than 2 consecutive visits or a total of 3 visits can be postponed 
by up to 14 days (inclusive) due to objective reasons (the patient cannot come to the study site 
due to force-majeure or any other justifiable reasons) or due to AEs. If the date of a visit with 
the investigational product administration has to be shifted by more than 3 days, dates of the 
subsequent injections also should be shifted. 
All cases when visits have to be shifted by the periods exceeding those specified above 
must be agreed with the Sponsor. 
 
 


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7. ASSESSMENT OF EFFICACY 
7.1 List of efficacy variables 
7.1.1. Definition of variables 
The patient is considered a PASI 75 responder if the PASI score improves by 75% from 
baseline. PASI 90 and PASI 100 responders are defined in the same way. 
7.1.2. Efficacy endpoints 
7.1.2.1. Primary endpoint 
• Proportion of patients who achieved PASI 75 at Week 12, by study arms. 
 7.1.2.2. Secondary endpoints in the main treatment period (Week 0 to Week 54): 
• Proportion of patients who achieved PASI 75/90/100 at Weeks 8, 16, 24, 42 and 
52, by study arms.  
• Proportion of patients with sPGA score 0 or 1 at Weeks 8, 12, 16, 24, 42, and 52. 
• Proportion of patients with sPGA score 0 at Weeks 16, 24, 42, and 52. 
• Relative change from baseline in PASI score at Weeks 8, 12, 16, 24, 42 and 52. 
• Change from baseline in itch severity measured with visual analog scale (0 mm to 
100 mm) at Weeks 1, 12, 24, and 52. 
• Change from baseline in Nail Psoriasis Severity Index (NAPSI) score at Week 12, 
24, and 52. 
• Change from baseline in Dermatology Life Quality Index (DQLI) score at Weeks 
8, 12, 24, 42, and 52. 
• Proportion of patients with DLQI score 0 or 1 at Weeks 24, 42, and 52. 
• Proportion of patients (among those with psoriatic arthritis) who achieved an 
ACR20/50/70 at Weeks 12, 24, and 52. 


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7.1.2.3. Efficacy endpoints during the extension study period (Week 54 through Week 166) 
• Proportion of patients who maintained PASI 75/90/100 response after 62, 74, 86, 
98, 110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 
• Proportion of patients who maintained sPGA 0-1 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 
• Proportion of patients who maintained sPGA score 0 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of 
treatment with BCD-085. 
• Proportion of patients who maintained DLQI score 0-1 after 62, 74, 86, 98, 110, 
122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of treatment 
with BCD-085. 
• Time to loss of PASI 75/90/100, sPGA 0-1/sPGA 0, DLQI 0-1 response during 
the treatment with BCD-085. 
• Proportion of patients who maintained ACR 20/50/70 response (among patients 
with psoriatic arthritis) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of 
treatment vs. response after 52 weeks of treatment with BCD-085. 
• Proportion of patients who achieved PASI 75/90/100 response after 62, 74, 86, 98, 
110, 122, 134, 146, and 154 weeks of treatment with BCD-085. 
• Proportion of patients with sPGA score 0 or 1 after 62, 74, 86, 98, 110, 122, 134, 
146, and 154 weeks of the treatment with BCD-085. 
• Proportion of patients who achieved sPGA score 0 after 62, 74, 86, 98, 110, 122, 
134, 146, and 154 weeks of treatment with BCD-085. 
• Change from baseline in itch severity measured with visual analog scale (0 mm to 
100 mm) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment with 
BCD-085. 
• Change from baseline in Nail Psoriasis Severity Index (NAPSI) score after 62, 74, 
86, 98, 110, 122, 134, 146, and 154 weeks of treatment with BCD-085 (among 
patients with nail psoriasis at baseline). 


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• Proportion of patients who achieved DLQI score 0 or 1 after 62, 74, 86, 98, 110, 
122, 134, 146, and 154 weeks of treatment with BCD-085. 
• Change from baseline in Dermatology Life Quality Index (DQLI) score after 62, 
74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment with BCD-085. 
7.2 Methods and timeframes for assessment, documenting, and analysis of efficacy variables 
7.2.1 Timeframes for analysis of efficacy variables 
The efficacy analysis by the primary endpoint (PASI 75) will be performed after 12 weeks 
of blinded therapy with BCD-085/placebo. 
The timing for 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 
The efficacy will be assessed in the ITT (intent-to-treat) population, which includes all 
randomized patients. 
In addition, the efficacy can be evaluated in the PP (Per Protocol) population, which 
includes those patients who completed all visits without major protocol deviations. 


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8. ASSESSMENT OF SAFETY 
8.1. List of safety variables 
8.1.1. Terms and 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 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 the first dose of the investigational 
product and until the end of the protocol-specified follow-up period.  
Negative medical events that occurred before the administration of the investigational 
product (including those found at Visit 1 but before the administration of the investigational 
product) are not considered to be adverse events. These conditions are background for this patient. 
8.1.1.2. Serious adverse events 
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: 
• 
Results in death; 
• 
Is life-threatening; 
• 
Requires hospitalization or prolongation of existing hospitalization; 
• 
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 a serious adverse event. 
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 that resolved without any signs of hepatic insufficiency will not 
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an allergic reaction resulting in face angioedema will not be considered life-threatening despite 
the fact that larynx angioedema, allergic bronchospasm or anaphylaxis may lead to a 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 AE should not be reported by the 
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 the study file. 
• Hospitalization because of a previous condition (recorded before the patient 
signed the ICF), for example, hospitalization for kidney transplantation because 
a donor organ has become available, surgery for cataract diagnosed before the 
patient signed the ICF, etc. 
Disability is defined as a significant or persistent loss of the ability to work because of a 
disease, injury, their consequences or other reasons during a definite period (temporary disability) 
or a long indefinite period. 
Other reportable information. Certain information not considered an SAE must be 
recorded, presented in the report, and followed up as an SAE. This includes:  
• Drug administration errors, such as unintended or accidental use, whether or not associated 
with an AE (including confusion or possible confusion during the administration of investigational 
products).  
• Overdose. 
• Pregnancy in study subjects or their sex partners. 
 
8.1.1.3. Unexpected adverse events 
Unexpected adverse reaction is an adverse reaction, the nature or severity of which is not 
consistent with the applicable product information (Investigator’s Brochure). 


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8.1.2. Safety endpoints 
• Proportion of patients who developed AEs/SAEs. 
• Proportion of patients who developed injection site reactions. 
• Proportion of patients who developed Grade 3/4 AEs/SAEs. 
• Proportion of patients who discontinued the study due to AEs and/or SAEs. 
• Exposure adjusted incidence rate of AEs/SAEs during the extension study. 
8.2. Methods and timeframes for assessment, documenting and analysis of safety variables 
8.2.1. Timeframes for analysis of safety variables 
Tolerability and safety endpoints will be analyzed at Weeks 12 and 54 of the study. 
Information about serious adverse events will include data on SAEs developed from the 
time when the subject received the first dose of the investigational product until the time he/she 
completed the study (as planned or prematurely).  
SAEs that developed during screening will be analyzed separately. Formally, these 
occurrences are not considered adverse events, because they develop before the administration of 
the investigational product. However, they can show the safety of screening procedures or be a 
reason to reject the patient during the screening, so they should be recorded.  
The adverse events that do not meet the seriousness criteria should be recorded starting 
from the moment when the investigational product was injected the first time until the end of the 
Protocol-defined follow-up period after the patient stopped taking the investigational product (as 
planned or prematurely). 
Drug Safety Division of JSC BIOCAD will analyze information about every SAE 
immediately after receiving an SAE report, provided that the investigator sent the report(-s) within 
the due time window. The cumulative analysis will be performed during the preparation of the 
final study report. 
AEs not meeting the seriousness criteria will be analyzed routinely during the preparation 
of the final study report. 


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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 data and vital signs, 
- CBC, blood chemistry, and urinalysis results, 
- ECG findings. 
The frequency of these procedures is specified in section 4.6.1 “Schedule of study visits 
and procedures”. AEs/SAEs will be documented and reported in accordance with the Sponsor’s 
Manual. 
The investigator is responsible for recording adverse events in the clinical study. 
AEs are recorded beginning from the moment when the investigational product was 
injected the first time until the end of the follow-up period after the patient stopped taking the 
investigational product (as planned or prematurely). SAEs are recorded from the moment when 
the subject signed the informed consent form until the moment when he/she completed the study 
(as planned or prematurely). SAEs that were recorded during screening are not included in the 
total safety analysis. The Investigator can record an SAE later than stipulated by the Protocol if 
he/she believes that this SAE is related to the investigational product or study procedures. 
An AE is considered to be resolved if the laboratory parameter, vital sign or symptom has 
returned to its baseline value. For all parameters, the baseline level is considered the value/sign 
severity that was seen in this patient before the first injection of BCD-085/placebo at the first 
scheduled visit per protocol. For AEs, including SAEs, of long-lasting/chronic nature, the 
resolution is the stabilization of the patient’s condition. For example, the AE “aggravation of 
chronic bronchitis” is considered to be resolved when the patient has achieved remission. 
The Investigator must document non-serious AEs in the source documents and in the CRF, 
and show them to the Monitor at the next monitoring visit. Besides being recorded in the source 
documents and eCRF, serious adverse events (SAEs) must be reported to the Sponsor within 24 h 
in the SAE Report Form. SAE Report Forms must be sent to the Sponsor within 24 h by email to 


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 (email subject: “For Pharmacovigilance Officer”). The investigator should 
receive a receipt/delivery confirmation. 
8.3 Requirements for reports, procedures for registration and reporting AEs, and filling out 
AE Report Forms 
8.3.1. Recording AEs/SAEs 
At every visit, a record should be made whether or not any AE occurred during the period 
from the previous visit. Any adverse event reported for a patient since he/she signed an informed 
consent form had to be recorded in source documents and in a special form for registration of 
adverse events (attachment to the CRF). AEs will be documented in accordance with the Sponsor’s 
Manual. 
AEs are recorded and numbered consecutively as they occur. Each AE is reported in an AE 
Report Form. Rules for documenting AE/SAE are described in detail in the Sponsor’s Manual. 
Adverse events must be recorded regardless of their seriousness and causal relationship 
with the study therapy. If an adverse event re-emerges, it should be recorded as a new AE and 
assigned a new number. 
Laboratory and vital sign abnormalities 
Laboratory and/or 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) must be recorded in the 
CRF, Adverse Events section. CTCAE 4.03 grade 1 adverse events are registered only if the 
investigator considers the event clinically meaningful. Starting from CTCAE 4.03 grade 2, all 
adverse events should be recorded, regardless of their clinical significance. It is preferable to 
specify diagnosis rather than individual symptoms (for example, anemia instead of reduced 
hemoglobin). Laboratory abnormalities meeting the criteria for an adverse event should be 
followed up until they return to normal or until an adequate explanation is obtained.  
Special rules for AE registration 
• Aggravation or worsening of the main disease or any symptoms of the main disease 
are not reportable as AEs even if they have any seriousness criteria. The event 
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criterion, while the AE is represented by worsened signs or aggravation of the main 
disease. 
• If the patient had no clinical/laboratory abnormalities at baseline, any grade 2 or 
higher (grade 1 or higher if the investigator considers it clinically meaningful) 
clinical/laboratory abnormality must be documented as an AE. If the patient had 
clinical/laboratory or other abnormalities at baseline, any increase in severity of this 
abnormality or any other worsening judged by the Investigator as clinically 
meaningful must be reported as an AE. 
• The event should not be documented as an SAE if hospitalization is the only 
seriousness criterion, while the AE is represented by worsened signs or aggravation 
of the main disease. 
• Cases of confirmed125 positive results of Diaskintest, QuantiFERON or T-spot are 
recorded as adverse events. 
Injection site reactions 
In this clinical study, investigators will evaluate injection site reactions after the 
administration of BCD-085/placebo. Assessments will be performed on the same visits when 
injections will be given. Assessment includes visual examination of the injection site (and sites 
where injections were given in the past if this is not the first visit) and collection of patient’s 
complaints. The Injection Site Reaction Form is presented in Annex 1. The Injection Site Reaction 
Report Form should be filled out only if an injection site reaction is recorded (starting from grade 
1). If there are no injection site reactions, this form is not filled out. Injection site reactions of grade 
2 or higher must be registered as adverse reactions. If the investigator considers a grade 1 injection 
site reaction to be clinically meaningful, it also must be registered as an adverse event. Severity 
grades for injection site reactions are presented in Annex 1. 
Among other laboratory/vital sign/clinical abnormalities not found at Visit 1 before 
the first injection of the investigational product, the following is recorded: 
• All abnormalities of CTCAE 4.03 grade 2 and higher. 
• Grade 1 abnormalities should be recorded as AEs only if clinically relevant, i.e. if the 
Investigator considers the abnormality to be substantial with account of the main and 
concurrent illnesses. Single abnormalities found among multiple laboratory test results or 
                                                          
125 If retest is performed, its results are considered. 


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incidental low values should not be reported as AEs, except for events that are clinically 
relevant. 
If revealed during the period between scheduled visits (for example, when the patient 
comes to the study site for dialysis), a laboratory/vital sign/instrumental abnormality can be 
recorded by the Investigator in the eCRF if clinically meaningful (regardless of its severity grade). 
The Investigator specifies the onset date, the fact that the AE occurred between visits, and the 
reason why the AE was recorded (for example, numerical values of laboratory and/or vital signs). 
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 no data are available, “Data not available” or “N/A” are put. However, 
all actions should be taken to receive all necessary data on emerging adverse events. 
The following information is recorded in source documents and the AE Report Form of the 
CRF: 
- Sec. No. of AE, 
- Visit number, 
- A brief description of the AE, 
- Serious (yes/no), 
- Seriousness criteria (if applicable), 
- Severity grade and highest severity grade according to CTCAE 4.03, 
- Onset date, 
- End date, 
- Outcome, 
- Actions taken, 
- Causality, 
- Comments specifying any clinically relevant (in the Investigator’s opinion) information 
related to AE development or therapy. 
If a medication therapy was administered, its components are described in section 
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Columns Grade, Outcome, Measures, and Causal Relationship are filled using digital 
codes explained in the Notes section. If the investigator considers an AE to be an SAE, he/she fills 
out an SAE Report Form in addition to the AE Report Form (printed copies). 
One SAE Report Form is filled out for one SAE. If the AE remains unresolved at the next 
visit, the checkbox in the Adverse Events section of the eCRF should be ticked for this visit and 
marked as “unresolved”. If any new important information has become available, a follow-up SAE 
Report Form should be filled out and sent to the Sponsor. If no new information about the SAE is 
available, the recommended frequency of reporting is once every 14 days.  
The following information should be recorded in the SAE Report Form: 
1) Clinical study: 
- Protocol ID, 
2) SAE information: 
- SAE name, 
- Initial or follow-up, 
- Internal SAE code assigned by the Sponsor (this field is filled out by the Sponsor) 
3) SAE reporting investigator and study site: 
- Full name of the investigator who reported the SAE 
- Contact information (tel. and e-mail) 
- Site name and code 
- Full name of the Principal Investigator 
4) Information on the study subject: 
- Subject’s number 
- Sex 
- Body weight 
- Height 
- Date of birth 
- Renal/hepatic impairment 
- Allergies 
5) Information on the test drug: 
- Code (or trade name) of investigational product 
- Indication 
- Date of the first dose 


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- Batch of the investigational product (after which the event developed) 
- Dose (with which the event occurred) 
- Treatment start date and time (followed by the event) 
- Treatment stop date and time (followed by the event) 
- Route of administration 
- Doses and dosing frequency 
6) Information about recent (within one month) concomitant therapy or one used at the 
time of SAE onset: 
- INNs and brand names of concomitant medications 
- Indication 
- Start date 
- End date 
- Doses, frequency and route of administration 
- Any suspected causal relationship between the SAE and concomitant medications 
7) SAE narrative: 
- SAE description with all symptoms and laboratory/instrumental abnormalities and 
time frames indicated. 
- Time after the last dose of the investigational product  
- Autopsy data if the subject died (specify the cause of death according to postmortem 
report). 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 the onset of the SAE 
- Investigation 
- Normal limits 
- Date of the analysis 
- Result 
12) Actions taken to resolve the SAE 
- Medications/other 


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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 reduced/unchanged etc. 
- 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. 
8.3.3. Reporting cases of study subject’s pregnancy/study subject’s partner’s pregnancy 
In this study, the Investigator must report to the Sponsor all cases of study subject’s 
pregnancy/study subject’s partner’s pregnancy that occurred during the study treatment period and 
follow-up after the last injection of BCD-085/placebo. 
The forms are filled out in the following cases: 
• When the initial information about the study subject’s pregnancy/study subject’s partner’s 
pregnancy is obtained; 
• When new important information (follow-up report) about the pregnancy (its 
complications or outcome) is obtained;  
• In 6 months after the delivery, so that the baby’s condition can be assessed. 
The report about pregnancy NOT associated with an SAE should be sent to the Sponsor by 
e-mail to
 within 5 working days. 
If an SAE has developed during pregnancy, the Pregnancy Form with the information about 
the SAE must be sent to the Sponsor within 24 h after this information became available. 
8.3.4. Recording administration errors with the investigational product 
Administration errors with the investigational product refer to any violation of dosing, 
route or procedure of administration described in the Study Protocol. This also includes violation 
(prolongation) of the interval between the doses of the investigational product, except for the cases 
specified by the protocol.  
This form is filled out for all these errors except for overdoses. 


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If an administration error with the investigational product is associated with an SAE, an 
SAE Report Form should be also filled out. 
If an investigational product administration error is not associated with an SAE, the 
Investigator should send the form by email to safety@biocad.ru within 5 working days. 
If an administration error with the investigational product is associated with an SAE, two 
forms are filled out (SAE Report Form and IP Administration Error Report Form). Both forms 
must be sent to the Sponsor within 24 hours from the moment when this information became 
available. 
8.3.5. Reporting drug overdose 
In this study, an overdose is defined the following way: administration of BCD-085 at a 
single dose greater than 120 mg or shortening of the interval between two doses by more than 3 
days. Shortening the between-visit periods by 3 days or less is not considered an overdose. 
Criteria for expedited reporting in case of overdoses: 
• 
An overdose of 2-fold or more vs. the dose prescribed by the Investigator must be reported 
as part of expedited reporting whether it is associated with an AE/SAE or not; 
• 
An overdose of less than 2-fold associated with an AE/SAE with a reasonable temporal 
relationship to the overdose also requires expedited reporting; 
• 
An overdose of less than 2-fold not associated with AEs/SAEs may be reported to the 
Sponsor as part of expedited reporting if, in the opinion of the Investigator, this event is 
meaningful; 
If the Investigator did not report an overdose of less than 2-fold using expedited reporting, 
the overdose should be recorded by the CRA only in the Deviations Log. 
8.4. Methods and duration of follow-up for study subjects after the onset of AE/SAE 
If the patient is withdrawn from the study due to an AE/SAE, the investigator should 
perform further patient’s treatment and follow-up as per standard institutional practices for the 
treatment of the certain AE or SAE. The patient should be followed up until the AE/SAE resolves 
completely. In case of any laboratory, instrumental or vital sign abnormality, the patient should, 
if possible, be followed up until the event is completely resolved (or until the value is back to the 
baseline level). 
See section 5.4 for further details. 


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The patient withdrawn from the study due to pregnancy that occurred during the study 
should be monitored throughout 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 woman’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. The pregnancy 
course, its outcome, and the newborn are followed up only if the patient gives her consent in the 
written form. The consent should be signed by the patient and stored in the source documentation. 
Any time, the patient could refuse from the follow-up/providing information about her 
pregnancy/its outcome/the newborn. 
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 the 
woman’s health over the entire course of pregnancy. Monitoring should be performed via phone 
calls to attending Ob/Gyn Specialist once every 3 months to analyze the overall woman’s health, 
pregnancy course, and laboratory and instrumental findings including ultrasonic investigation. 
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. The pregnancy course, its outcome, and the newborn are followed up only if the woman 
gives her consent in the written form. The consent should be signed by the woman and stored in 
the source documentation. Any time, the woman may refuse from the follow-up/providing 
information about her pregnancy/its outcome/the newborn. 
8.5. Immunogenicity study 
To assess the immunogenic potential of the study treatment, the proportions of BAb- and 
NAb-positive patients will be estimated. 
The immunogenicity endpoints will be evaluated at Weeks 12, 24, 54, 86, 110, 134, 154 
(in patients of Arms 1 and 2) or 12, 24, 54, 64, 98, 122, 146, 166 (in patients of Arm 3). 
The immunogenicity analysis will include all patients who have received at least one dose 
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dose of BCD-085 and at least one evaluable (not missing/lost/spoiled) serum sample taken at 
subsequent visits.  
9. STATISTICS 
9.1. Description of statistical methods 
The statistical analysis will be performed using two-sided hypothesis tests. The statistical 
significance level is 0.05. 
To compare normally distributed data, it is planned to use the following tests: two-sample 
Student t-test, Welch’s test, and ANOVA. 
Non-normally distributed data will be compared with the following tests: Mann-Whitney 
test, Wilcoxon test, Kruskal-Wallis test, and Friedman test. 
The quantitative data: 
  Efficacy: 
• Relative PASI change,  
• Change in itch severity (VAS, 0 to 100 mm), 
• Change in NAPSI score, 
• Change in quality of life according to the DLQI score, 
• Time to loss of PASI 75/90/100, sPGA 0-1/sPGA 0, DLQI 0-1 response during the treatment 
with BCD-085. 
Safety: 
• CBC results, 
• Blood chemistry results. 
Demographics 
will be tested for the normality of distribution using the Shapiro-Wilk test. 
For normally distributed quantitative data, the following characteristics will be used: mean 
value, standard deviation, coefficient of variation, minimum and maximum. Non-normally 
distributed quantitative data will be described using median and quartiles, min and max values.  
The categorical data: 
Efficacy: 


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• Proportion of patients with PASI 75/90/100. 
• Proportion of patients with sPGA score 0 or 1. 
• Proportion of patients (among patients with psoriatic arthritis) who achieved an ACR20/50/70. 
• Proportion of patients who maintained ACR 20/50/70 response (among patients with psoriatic 
arthritis). 
• Proportion of patients who maintained DLQI score 0-1. 
Safety: 
• Proportion of patients who developed AEs/SAEs. 
• Proportion of patients who developed injection site reactions. 
• Proportion of patients who developed Grade 3/4 AEs/SAEs. 
• Proportion of patients who discontinued the study due to AEs and/or SAEs. 
• Exposure adjusted incidence rate of AEs/SAEs during the extension study.  
Immunogenicity: 
• Proportion of patients with anti-drug antibodies (binding/neutralizing) 
will be processed using the frequency tables, Fisher’s test, 𝜒𝜒2 test, and Cochran-Mantel-Haenszel 
test. The categorical data will be described using percentages or proportions. 
For multiple comparisons, the Benjamini-Yekutieli procedure will be used. 
Regression will be used to assess the effects of the factors other than the therapy type. Time to loss 
of response will be assessed using log-rank test, Kaplan-Meier curves, and Cox regression model. 
Time will be counted from the response during the treatment with BCD-085. Right censoring can 
be used to analyze time to events. 
Statistical methods will be chosen based on the type and distribution of raw data. 
Applicability of certain statistical tests will be evaluated after all the data are collected because it 
is impossible to predict the distribution pattern, data homogeneity and other data characteristics in 
advance.  
The data will be processed using programming language R for statistical processing and 
SAS 9.4 software environment. 


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9.2. Statistical analysis steps and timelines for reports 
 
 
  
 
 
 
 
 
 
 
 
 
9.3. Planned number of subjects. Justification of sample size, including reasoning or 
calculations to justify statistical power, and clinical justification of the study 
Two independent hypotheses will be tested during the study: 
1. The main study hypothesis (stating the non-inferiority of BCD-085 Q4W vs. BCD-085 
Q2W) will be tested at the significance level of 0.05; 
2. The hypothesis stating the superiority of BCD-085 in different dosing regimens over 
placebo will be tested at the significance level of 0.05. 
9.3.1. Non-inferiority hypothesis 
The sample size required to run the study was calculated on the basis of the literature data 
on clinical efficacy. During study planning, the hypothesis stating that BCD-085 Q4W is 
non-inferior to BCD-085 Q2W (H0:ε ≤𝛿𝛿, H1:ε > δ, where ε is true difference in the frequency of 
the efficacy variable between the arms, δ is non-inferiority margin) was tested with the following 
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9.6. Handling of missing, unevaluable or uncertain data 
All information specified in the eCRF should be confirmed by appropriate data in the 
source documents.  
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 Data Manager and Medical Expert generate queries, which are patient- and 
site-specific, i.e. generated for each subject individually. The CRA sends queries to the study site 
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 the queries are received from investigators, the employee keeping the 
database checks them for inconsistencies, errors, and missing data points When all the data from 
all the sites are collected and entered, the database is locked, and the statistical processing can be 
performed. 
Missing, unevaluable or uncertain data are not subject to replacement.  
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. 


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9.8. Selection of subjects for analysis 
Safety analysis 
The safety analysis will include all patients randomized in the study. 
Efficacy analysis 
The efficacy will be assessed in the ITT (intent-to-treat) population, which includes all 
randomized patients. 
In addition, the efficacy can be evaluated in the PP (Per Protocol) population, which 
includes those patients who completed all visits without major protocol deviations. 
Immunogenicity analysis 
The immunogenicity analysis will include all patients who have received at least one dose 
of BCD-085 and had an evaluable (not missing/lost/spoiled) serum sample taken before the first 
dose of BCD-085 and at least one evaluable (not missing/lost/spoiled) serum sample taken at 
subsequent visits.  
10. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The investigator/institution involved in the study must ensure direct access to source 
data/documents during monitoring, audits, ethics review, and inspections by regulatory authorities. 
11. QUALITY CONTROL AND QUALITY ASSURANCE 
11.1. Data quality assurance 
According to the ICH GCP and regulatory requirements, the Sponsor, a 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 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. Investigator’s adherence to the Protocol 
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 prior written permission from 
JSC BIOCAD, the Ministry of Healthcare of the Russian Federation, and the Local Ethics 
Committee, except when necessary to protect patients from an immediate hazard.  
The investigator should have enough time to accurately perform and complete the study 
within the timeframes 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 the 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 subject 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 CJSC 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 
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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. 
11.4. Study monitoring 
Study monitoring is performed according to the appropriate SOPs of JSC BIOCAD.  
The investigators must ensure that data are entered in the eCRFs in a timely manner, and 
must give the Sponsor’s representative (CRA) regular access to the eCRFs, patient medical 
records, and all other study materials. 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 completion of the study, the BIOCAD’s representative (Clinical Study Manager or 
CRA) will visit the study site for a closeout 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 studies 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. 
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 due to other reasons. If JSC BIOCAD suspends or terminates the study, the 
study site will be notified in advance. If JSC BIOCAD suspends or terminates the study, CJSC 
BIOCAD and the investigator must promptly inform the IRB/IEC and regulatory authorities. If the 


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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 set forth in the 
Helsinki Declaration of the World Medical Association, Russian Federal Law “On circulation of 
medicinal products” (FZ-61 dated April 12, 2010), Russian Decree N 200n dated April 01, 2016 
“On approval of Good Clinical Practice”, Russian National Standard “Good Clinical Practice” 
(GOST R 52379-2005), Good Clinical Practice of the Eurasian Economic Union, Constitution of 
the Russian Federation, Federal Law 323-FZ dated November 21, 2011 “On fundamental 
healthcare principles in the Russian Federation”, GCP and regulatory requirements of the 
participating countries. 
Before the study start, the final version of the Protocol, including Patient Information Sheet 
and Informed Consent Form, will be submitted for approval to Russian regulatory authorities 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 necessary. Local Ethics 
Committees will also be notified of all SAEs that are related, in the 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).  
All study subjects will be insured. If a subject gets injured directly due to the investigational 
product, the Sponsor will cover all reasonably justified treatment expenses. 


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12.2. Confidentiality of study subjects 
The Investigator shall protect the confidentiality of the study subjects, the text of this 
Protocol, and all other study materials and results.  
The Investigator must ensure subject 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 subjects’ IDs, last names, addresses, 
phone numbers, and medical record numbers (if applicable). The investigator must keep the 
confidentiality of the data not intended for submission to JSC BIOCAD. 
All study materials proprietary to JSC BIOCAD cannot 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 are the essential documents that 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 approval from JSC BIOCAD before destroying any of the essential documents. 
Appropriate measures must be taken to prevent 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 
informing study subjects and obtaining their written authorization regarding 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, if 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. If the patient recalls authorization to collect or use his/her 
protected health information, the investigator should do as much as possible to get patient’s 
permission for collecting at least the safety information (i.e. onset of new or aggravation of existing 
adverse events) until the scheduled end of the study period. 
To prevent unauthorized access to protected subject information, the data management 
system uses integrated safety elements encrypting all the data when sending them in both 
directions. The access to the system will be controlled via individually assigned ID codes and user 
passwords issued only to authorized and adequately trained personnel. 
 
 
 
 
 
 
 
 
 


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13.3. Collection of data 
This study 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 
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 the 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. 
14. REIMBURSEMENT AND INSURANCE 
Patients will not be paid for participation in this study. 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 
 
.  
The investigator will 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.  
The insurance covers claims of study subjects to the Insurer only for compensation for 
harm for their life and health during the participation in the clinical study. The insurance interest 
is the patient’s property interest related to harm for his/her life or health due to the clinical study 
in case of the causal relationship between the participation in the study and the insured event. 


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The Insurer shall pay the following compensation amounts according to the compulsory 
Insurance Agreement (insurance payment): 
a) In case of death of the insured person - 
. The insurance benefit is divided 
into equal parts and paid to beneficiary parties; 
b) If the insured person gets injured, and the injury results in: 
Group I disability: 
; 
Group II disability
; 
Group III disability: 
. 
c) If the insured person gets injured, and the injury does not result in disability: not more 
than 
. 
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 at his/her study site, 
without a permit from JSC BIOCAD. Results from individual study sites must not be published 
before the publication of the overall study results. 




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Annex 2. VAS for assessing itch severity (template) 


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Annex 3. VAS for assessing psoriatic arthritis (templates) 
1. Psoriatic arthritis activity assessed by the physician 
2. Patient assessment of pain 
 
 
 
 


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3. Psoriatic arthritis activity assessed by the patient 
 
 
 
 




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SAP_001.pdf: 
Statistical Analysis Plan 
Protocol Number: BCD-085-7 
CONFIDENTIAL 
Version 2.0 dated 05.06.2019 
Page 1 of 17 
STATISTICAL ANALYSIS PLAN 
Protocol Title: 
Protocol ID 
Protocol version 
Version Date 
SAP version 
SAP version date 
An International Multicenter, Randomized, Double-
blind, Placebo-controlled Clinical Study to Compare the 
Efficacy and Safety of Two Dosing Regimens of BCD-085 
(JSC BIOCAD, Russia) in Patients with Moderate to 
Severe Plaque Psoriasis 
BCD-085-7 
2.0 
02.11.2018 
2.0 
05.06.2019 
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.: 
Name and function of 
person(s), authorized to sign 
the protocol and its 
amendments for the sponsor: 
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.:
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. 


Statistical Analysis Plan 
Protocol Number: BCD-085-7 
CONFIDENTIAL 
Version 2.0 dated 05.06.2019 
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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 ....................................................................................................................................................... 4 
3. STUDY DESIGN ..................................................................................................................................................... 5 
3.1 DESIGN ................................................................................................................................................................ 5 
3.2 POPULATION ........................................................................................................................................................ 8 
4. EVALUATION CRITERIA ................................................................................................................................... 8 
4.1 EFFICACY ENDPOINTS .......................................................................................................................................... 8 
4.2. SAFETY ENDPOINTS .......................................................................................................................................... 10 
4.3. IMMUNOGENICITY ENDPOINTS .......................................................................................................................... 10 
5. THE PLANNED ANALYSIS ............................................................................................................................... 10 
6. SAMPLE SIZE CALCULATION ....................................................................................................................... 10 
7. ANALYSIS POPULATIONS ............................................................................................................................... 13 
8. ANALYSIS PLAN AND STATISTICAL METHODS ...................................................................................... 14 
8.1. THE SOFTWARE ................................................................................................................................................. 14 
8.2. DESCRIPTION OF THE STATISTICAL METHODS TO BE EMPLOYED ..................................................................... 14 
8.3. THE LEVEL OF SIGNIFICANCE TO BE USED ......................................................................................................... 16 
8.4. ACCOUNTING FOR MISSING, UNAVAILABLE OR DOUBTFUL DATA, OUTLIERS ..................................................... 16 
8.5. STATISTICAL EVALUATIONS FOR THE EARLY STUDY TERMINATION .................................................................. 16 
8.6. SUBGROUP ANALYSIS, INTERACTION AND RELATED VARIABLES ....................................................................... 17 
9. OTHER PLANNED ANALYSES ........................................................................................................................ 17 
10. DEVIATIONS FROM ANALYSIS METHODS DESCRIBED IN STUDY PROTOCOL .......................... 17 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
CONFIDENTIAL 
Version 2.0 dated 05.06.2019 
Page 3 of 17 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ACR 
American College of Rheumatology criteria of improvement in rheumatoid arthritis 
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 
HAQ-DI 
Health assessment questionnaire disability index 
ICF 
Informed consent form 
IL 
Interleukin 
ITT 
Intent-to-treat 
JSC 
Joint Stock Company 
MAb 
Monoclonal antibody 
NAb 
Neutralizing antibodies 
NAPSI 
Nail Psoriasis Severity Index 
PASI 
Psoriasis Area and Severity Index 
PP 
Per protocol 
Q2W 
Once every 2 weeks 
Q4W 
Once every 4 weeks 
QoL 
Quality of Life 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
sPGA 
Static Physicians Global Assessment 
TNF-α 
Tumor necrosis factor alpha 
UV 
Ultraviolet 
VAS 
Visual analogue scale 


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
CONFIDENTIAL 
Version 2.0 dated 05.06.2019 
Page 4 of 17 
1. INTRODUCTION
The Statistical Analysis Plan (SAP) provides a detailed analysis plan and steps of study 
report preparation for the clinical trial BCD-085-7. 
2. GOALS AND OBJECTIVES
2.1. Purpose 
To evaluate the efficacy and safety of BCD-085 once every 4 weeks vs. BCD-085 once 
every 2 weeks (standard dosing regimen) vs. placebo. 
2.2. Objectives 
Main study period 
1. To compare the efficacy of BCD-085 in two dosing regimens and placebo using PASI 75 rate,
sPGA score, and other secondary efficacy measures after 12 weeks of the treatment.
2. To compare the efficacy of BCD-085 in two dosing regimens and placebo using PASI 75 rate,
sPGA score, and other secondary efficacy measures after 52 weeks of the treatment.
3. To evaluate the proportion of patients in each study arm who developed adverse events with
repeated administration of BCD-085 or placebo. To compare the safety profiles of BCD-085
Q4W and BCD-085 Q2W.
4. To assess the immunogenicity of BCD-085 defined as the proportion of patients who
developed anti-drug antibodies (binding/neutralizing).
Extension study period 
1. To assess maintenance of response during the long-term treatment with BCD-085 (for up to
154 weeks) and evaluate the safety profile of such treatment.
2. To assess the immunogenicity of BCD-085 defined as the proportion of patients who
developed anti-drug antibodies (binding/neutralizing).
2.3. Hypothesis 
Two independent hypotheses will be tested during the study: 
−
BCD-085 Q4W is not less effective than BCD-085 Q2W,
−
The efficacy of BCD-085 in both regimens is superior to placebo.


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
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Version 2.0 dated 05.06.2019 
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3. STUDY DESIGN
3.1 Design 
The BCD-085-7 study is an international multicenter, randomized, double-blind, placebo-
controlled clinical study to evaluate the efficacy and safety of two dosing regimens of BCD-085 
(JSC BIOCAD, Russia) in patients with moderate to severe plaque psoriasis (Phase III). 
The study is planned to enroll 213 adult patients with moderate to severe plaque psoriasis 
(diagnosed at least 6 months before signing the informed consent form) who have BSA ≥ 10%, 
PASI score ≥ 10, and sPGA score ≥ 3. 
Before being screened for the study, patients must read and sign the informed consent form 
and undergo a screening examination (within 28 calendar days) to confirm that they are eligible 
for the study. The Protocol does not provide any additional requirements regarding the diet or 
physical activity during the screening or study period. 
Stratification and randomization 
When the Investigator has decided that the patient can take part in the study, the patient 
should be stratified according to his/her body weight (<100 kg/≥100 kg), previous use of 
monoclonal antibodies for the treatment of psoriasis (previously treated/naive), PASI score 
(<20/≥20), and psoriatic arthritis (yes/no) and randomized at a 2:2:1 ratio to one of the three study 
groups: 1) BCD-085 Q2W (Arm 1), 2) BCD-085 Q4W (Arm 2), 3) placebo (Arm 3). 
Study periods 
1. Screening (up to 28 days from signing the Patient Information Sheet with the Informed Consent
Form, inclusive).
2. Main treatment period (from Week 0 through Week 54, inclusive).
3. Extension treatment period:
1) for Arms 1 and 2: from Week 54 through Week 154,
2) for Arm 3: from Week 54 through Week 166.
4. Follow-up period:
1) for Arms 1 and 2: from Week 154 through Week 158,
2) for Arm 3: from Week 166 through Week 170.


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
CONFIDENTIAL 
Version 2.0 dated 05.06.2019 
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Screening period: 
Up to 28 days from signing the Patient Information Sheet with the Informed Consent Form, 
inclusive. 
Main treatment period (Week 0 through Week 54): 
In this study period patients will be distributed to three arms: 
•
Arm 1: Patients in this arm (85 subjects) will receive BCD-085 120 mg (two subcutaneous
injections, 60 mg in 1.0 mL each) once a week during the first 3 weeks (induction) and then
once every 2 weeks through Week 10. Thus, the investigational product will be administered
on Day 1 of Week 0, Week 1, Week 2, Week 4, Week 6, Week 8, and Week 10.
•
Arm 2: Patients in this arm (85 subjects) will receive BCD-085 120 mg (two subcutaneous
injections, 60 mg in 1.0 mL each) once a week during the first 3 weeks (induction) and then
once every 4 weeks through Week 10. Thus, the investigational product will be administered
on Day 1 of Week 0, Week 1, Week 2, Week 6 and Week 10. To maintain the study blind,
patients of this arm will receive placebo (2 injections) on Day 1 of Week 4 and Week 8.
•
Arm 3: Patients of this arm (43 subjects) will receive placebo (2 subcutaneous injections of
placebo, 1.0 mL each) on Day 1 of Week 0, Week 1, Week 2, Week 4, Week 6, Week 8 and
Week 10.
On Week 12, the treatment efficacy will be assessed with a PASI 75 score, and the treatment 
will be unblinded. Patients from Arms 1 and 2 will be given BCD-085 once every 4 weeks. 
Patients from Arm 3 will receive BCD-085 as follows:  
✓Induction: Weeks 12, 13, and 14, once a week;
✓Weeks 18 through 50: once every 4 weeks.
Therefore, there will be 3 arms even after unblinding, and patients will receive BCD-085
according to the regimens described below: 
a) Patients in Arm 1 will receive BCD-085 120 mg (2 subcutaneous injections of 60 mg each) once
every 4 weeks starting from Week 14 through Week 50. 
b) Patients in Arm 2 will receive BCD-085 120 mg (2 subcutaneous injections of 60 mg each)
once every 4 weeks starting from Week 14 through Week 50. 


Statistical Analysis Plan 
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с) Patients in Arm 3 will receive BCD-085 120 mg once a week at Weeks 12, 13, 14, then once 
every 4 weeks (Weeks 18, 22, 26, 30, 34, 38, 42, 46, 50). 
Extension study period (from Week 54 through Week 154 for Arms 1 and 2, through Week 
166 for Arm 3): 
During the extension study period all patients who achieved PASI 75 at Week 52 will 
receive BCD-085 120 mg once every 4 weeks: 
a) Patients from Arm 1 will receive BCD-085 from Week 54 through Week 154.
b) Patients from Arm 2 will receive BCD-085 from Week 54 through Week 154.
c) Patients from Arm 3 will receive BCD-085 from Week 54 through Week 166.
Patients who failed to achieve PASI 75 at Week 52 will be withdrawn from the study. 
In Arm 3, treatment will be extended by 12 weeks so that the total treatment duration in all 
arms can be 154 weeks. During the main treatment period (during the first 12 weeks of the study), 
patients from Arm 3 receive placebo, so the treatment period for these patients is extended to 166 
weeks. 
Regardless of the arm where the patient is assigned to, during the main study period (Week 
0 through Week 54) subcutaneous injections will be performed by an authorized member of the 
study team at the study site (except for the injection on Week 54). 
At Week 54 patients will be trained on how to self-inject the investigational product. If 
necessary, the training can be repeated at any of the subsequent visits. 
During the extension study period (Week 54 through Week 154 for patients from Arms 1 
and 2, Week 54 to Week 166 for patients from Arm 3), patients will self-inject the investigational 
product at home after receiving relevant training at the study site. Injections of the investigational 
product on visit dates will be performed by an authorized member of the study team at Weeks 62, 
74, 86, 98, 110, 122, 134, 146, 154 (in Arms 1 and 2) or at Weeks 62, 74, 86, 98, 110, 122, 134, 
146, 154, 166 (in Arm 3). The first self-injection of the investigational product at Week 54 will be 
performed under the supervision of an authorized member of the study team. Patients from Arms 
1 and 2 will self-inject the investigational product on Day 1 of Weeks 58, 66, 70, 78, 82, 90, 94, 


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Protocol Number: BCD-085-2 
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102, 106, 114, 118, 126, 130, 138, 142, 150, patients from Arm 3 – on Day 1 of Weeks 58, 66, 70, 
78, 82, 90, 94, 102, 106, 114, 118, 126, 130, 138, 142, 150, 158, 162. 
At each of visits from Week 54 to Week 146 (patients from Arms 1 and 2) and at each of 
visits from Week 54 to Week 154 (patients from Arm 3), BCD-085 will be dispensed to patients 
for self-administration at home at an amount sufficient until the next visit. 
Follow-up period: 
Patients will be followed up for 4 weeks after the last injection (Week 154 to Week 158 
for Arms 1 and 2, Week 166 to Week 170 for Arm 3). 
3.2 Population 
Men and women aged from 18 years (inclusive) and older with a confirmed diagnosis of 
moderate to severe plaque psoriasis (lasting for at least 6 months before signing the ICF) who did 
not respond to/are candidates for systemic therapy including TNF-α inhibitors or UV therapy. 
4. EVALUATION CRITERIA
4.1 Efficacy endpoints 
Primary endpoint 
−
Proportion of patients who achieved PASI 75 at Week 12, by study arms.
Secondary endpoints in the main treatment period (Week 0 to Week 54): 
−
Proportion of patients who achieved PASI 75/90/100 at Weeks 8, 16, 24, 42 and 52, by
study arms.
−
Proportion of patients with sPGA score 0 or 1 at Weeks 8, 12, 16, 24, 42, and 52.
−
Proportion of patients with sPGA score 0 at Weeks 16, 24, 42, and 52.
−
Relative change from baseline in PASI score at Weeks 8, 12, 16, 24, 42 and 52.
−
Change from baseline in itch severity measured with visual analog scale (VAS) (0 mm to
100 mm) at Weeks 1, 12, 24, and 52.
−
Change from baseline in Nail Psoriasis Severity Index (NAPSI) score at Week 12, 24, and
52.
−
Change from baseline in Dermatology Life Quality Index (DLQI) score at Weeks 8, 12, 24,
42, and 52.
−
Proportion of patients with DLQI score 0 or 1 at Weeks 24, 42, and 52.


Statistical Analysis Plan 
Protocol Number: BCD-085-2 
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Version 2.0 dated 05.06.2019 
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−
Proportion of patients (among those with psoriatic arthritis) who achieved an ACR20/50/70
at Weeks 12, 24, and 52.
Secondary endpoints during the extension study period (Week 54 through Week 166): 
−
Proportion of patients who maintained PASI 75/90/100 response after 62, 74, 86, 98, 110,
122, 134, 146, and 154 weeks of treatment vs. response after 52 weeks of treatment with
BCD-085.
−
Proportion of patients who maintained sPGA 0-1 response after 62, 74, 86, 98, 110, 122,
134, 146, and 154 weeks of treatment vs. response after 52 weeks of treatment with BCD-
085.
−
Proportion of patients who maintained sPGA score 0 response after 62, 74, 86, 98, 110, 122,
134, 146, and 154 weeks of treatment vs. response after 52 weeks of treatment with BCD-
085.
−
Proportion of patients who maintained DLQI score 0-1 after 62, 74, 86, 98, 110, 122, 134,
146, and 154 weeks of treatment vs. response after 52 weeks of treatment with BCD-085.
−
Time to loss of PASI 75/90/100, sPGA 0-1/sPGA 0, DLQI 0-1 response during the
treatment with BCD-085.
−
Proportion of patients who maintained ACR 20/50/70 response (among patients with
psoriatic arthritis) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment vs.
response after 52 weeks of treatment with BCD-085.
−
Proportion of patients who achieved PASI 75/90/100 response after 62, 74, 86, 98, 110,
122, 134, 146, and 154 weeks of treatment with BCD-085.
−
Proportion of patients with sPGA score 0 or 1 after 62, 74, 86, 98, 110, 122, 134, 146, and
154 weeks of the treatment with BCD-085.
−
Proportion of patients who achieved sPGA score 0 after 62, 74, 86, 98, 110, 122, 134, 146,
and 154 weeks of treatment with BCD-085.
−
Change from baseline in itch severity measured with visual analog scale (VAS) (0 mm to
100 mm) after 62, 74, 86, 98, 110, 122, 134, 146, and 154 weeks of treatment with BCD-
085.
−
Change from baseline in Nail Psoriasis Severity Index (NAPSI) score after 62, 74, 86, 98,
110, 122, 134, 146, and 154 weeks of treatment with BCD-085 (among patients with nail
psoriasis at baseline).
−
Proportion of patients who achieved DLQI score 0 or 1 after 62, 74, 86, 98, 110, 122, 134,
146, and 154 weeks of treatment with BCD-085.


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−
Change from baseline in Dermatology Life Quality Index (DLQI) score after 62, 74, 86, 98,
110, 122, 134, 146, and 154 weeks of treatment with BCD-085.
4.2. Safety endpoints 
−
Proportion of patients who developed AEs/SAEs.
−
Proportion of patients who developed injection site reactions.
−
Proportion of patients who developed Grade 3/4 AEs/SAEs.
−
Proportion of patients who discontinued the study due to AEs and/or SAEs.
−
Exposure adjusted incidence rate of AEs/SAEs during the extension study.
4.3. Immunogenicity endpoints 
−
Proportion of patients with anti-drug antibodies (binding/neutralizing).
5. THE PLANNED ANALYSIS
Final report 
The final report will contain results of the efficacy and safety endpoint analysis by study 
arms after the 12-week blinded treatment period (Week 0 to Week 12) in 213 study subjects. 
Supplementary reports 
Supplementary Report 1 will contain results of the efficacy and safety endpoint analysis by 
study arms after 54 weeks of the study. 
Supplementary Report 2 will contain results of the efficacy and safety endpoint analysis 
after 2 years of the study treatment (110 weeks in patients from Arms 1 and 2, 122 weeks in 
patients from Arm 3). 
Supplementary Report 3 will contain results of the efficacy and safety endpoint analysis 
after 3 years of the study treatment (158 weeks in patients from Arms 1 and 2, 170 weeks in 
patients from Arm 3). 
6. SAMPLE SIZE CALCULATION
Two independent hypotheses will be tested one after another: 
1. The main study hypothesis (stating the non-inferiority of BCD-085 Q4W vs. BCD-085
Q2W) will be tested at the significance level of 0.05;


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2. The hypothesis stating the superiority of BCD-085 in different dosing regimens over
placebo will be tested at the significance level of 0.05.
6.1. Non-inferiority hypothesis 
The sample size required to run the study was calculated on the basis of the literature data 
on clinical efficacy. During study planning, the hypothesis stating that BCD-085 Q4W is 
noninferior to BCD-085 Q2W (H0: ε ≤𝛿, H1: ε > δ, where ε is true difference in the frequency of 
the efficacy variable between the arms, δ is non-inferiority margin) was tested with the following 
error values: type I error of 5% (α=0.05), type II error of 20% (β=0.2), power of test of 80%. The 
efficacy endpoint used to calculate the sample size was PASI 75 rate by Week 12 in each arm 
. 
The superiority margin was calculated using the 95% confidence interval for the difference 
in rates between the BCD-085 Q2W and placebo arms. 
According to [Design and Analysis of Non-Inferiority Trials, M.D. Rothman, Wiens, 
2012], the superiority margin can be set as half of the lower bound of the 95% CI for the difference 
in efficacy parameter values of the active drug and placebo. 


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6.2. Superiority hypothesis 
Sample size for superiority testing 
During study planning, the hypotheses stating that BCD-085 Q4W and BCD-085 Q2W are 
superior to placebo (H01: ε2𝑤≤𝛿, H11: ε2𝑤> δ; H02: ε4𝑤≤𝛿, H12: ε4𝑤> δ, where ε2w, ε4w is the 
true difference in the rate of the efficacy variable between the arms treated with BCD-085 Q2W 
and with BCD-085 Q4W, respectively, δ is the superiority margin for BCD-085 over placebo) 
were tested with the following error values: type I error of 5% (α=0.05), type II error of 20% 
(β=0.2), power of test of 80%. The efficacy endpoint used to calculate the sample size was PASI 
75 rate by Week 12 in each arm 
The sample size needed to test the superiority hypotheses was calculated using the method 
described by [Chow Sh.-Ch., Shao J., Wang H., 2008]: 


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Thus, the study should include at least 193 patients (77 in each BCD-085 arm and 39 in 
placebo arm). With a potential dropout rate of 10%, the study should involve 213 patients (85 
patients in each BCD-085 arm and 43 patients in the placebo arm). 
7. ANALYSIS POPULATIONS
Safety analysis 
The safety analysis will include all patients randomized in the study (intent-to-treat (ITT) 
population). 
Efficacy analysis 
The efficacy will be assessed in the ITT (intent-to-treat) population, which includes all 
randomized patients. In addition, the efficacy can be evaluated in the PP (Per Protocol) population, 
which includes those patients who completed all visits without major protocol deviations. 


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Immunogenicity analysis 
The immunogenicity analysis will include all patients who have received at least one dose 
of BCD-085 and had an evaluable (not missing/lost/spoiled) serum sample taken before the first 
dose of BCD-085 and at least one evaluable (not missing/lost/spoiled) serum sample taken at 
subsequent visits. 
Main demographics, baseline clinical and laboratory parameters obtained on the screening 
will be processed using descriptive statistics and will be analyzed in the efficacy and safety 
populations. 
8. ANALYSIS PLAN AND STATISTICAL METHODS
8.1. The software 
Statistical processing of the data will be performed using R programming language for 
statistical computing and SAS 9.4 environment. 
8.2. Description of the Statistical Methods to be Employed 
The statistical analysis will be performed using two-sided hypothesis tests. The statistical 
significance level is 0.05. 
The study hypothesis of non-inferior efficacy of BCD-085 once every 4 weeks vs. BCD-
085 once every 2 weeks will be proved by comparing the lower bound of the 95% confidence 
interval for the difference in proportions of patients with PASI 75 at Week 12 between the BCD-
085 Q4W and BCD-085 Q2W with pre-specified non-inferiority margin (δ) equal to -20.38%. 
The hypothesis stating the superior efficacy of BCD-085 over placebo will be proved by 
comparing the lower bound of the 95% confidence interval for the difference in proportions of 
patients with PASI 75 by Week 12, in each BCD-085 arm and placebo arm, with pre-specified 
non-inferiority margin (δ, 0%). 
Quantitative Data 
The following quantitative data will be analyzed in the study: 
Efficacy: 
−
Relative PASI change,
−
Change in itch severity (VAS, 0 to 100 mm),
−
Change in NAPSI score,
−
Change in quality of life according to the DLQI score,


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−
Time to loss of PASI 75/90/100, sPGA 0-1/sPGA 0, DLQI 0-1 response during the
treatment with BCD-085,
Safety: 
−
CBC results,
−
Blood chemistry results,
−
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), quality of life
score (DLQI), the presence of depression (Beck’s score), functional activity (HAQ-
DI), tender joint count (of 68) , swollen joint count (of 66).
Quantitative data will be described using the following descriptive statistics: mean, SD, 
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. 
Time to loss of response will be assessed using log-rank test, Kaplan-Meier curves, and 
Cox regression model. Time will be counted from the response during the treatment with BCD-
085. Right censoring can be used to analyze time to events.
Categorical Data 
The following categorical data will be analyzed in the study: 
Efficacy: 
−
Proportion of patients with PASI 75/90/100,
−
Proportion of patients with sPGA score 0 or 1,
−
Proportion of patients with DLQI score 0 or 1,
−
Proportion of patients (among patients with psoriatic arthritis) who achieved an
ACR20/50/70,
−
Proportion of patients who maintained PASI 75/90/100 score,
−
Proportion of patients who maintained sPGA score 0 or 1,


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−
Proportion of patients who maintained DLQI score 0 or 1,
−
Proportion of patients who maintained ACR 20/50/70 response (among patients
with psoriatic arthritis).
Safety: 
−
Proportion of patients who developed AEs/SAEs,
−
Proportion of patients who developed injection site reactions,
−
Proportion of patients who developed Grade 3/4 AEs/SAEs,
−
Proportion of patients who discontinued the study due to AEs and/or SAEs,
−
Exposure adjusted incidence rate of AEs/SAEs during the extension study.
Immunogenicity: 
−
Proportion of patients with anti-drug antibodies (binding/neutralizing).
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,
−
Medical history.
Extent of exposure: 
−
The number of administrations given during the study,
−
Exposure of BCD-085 with mean daily dose and treatment duration.
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. 
8.3. The level of significance to be used 
The level of significance is set as 0,05 (5%) with statistical power of 0,8 (80%). 
8.4. 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. 
8.5. Statistical evaluations for the early study termination 


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Not available. 
8.6. Subgroup analysis, interaction and related variables 
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.