A Phase 2b Randomized, Double-blind, Placebo Controlled, Multi-center 12-week Study With an Additional 40-week Follow-up Assessment of Efficacy, Safety and Tolerability of M1095 in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis
Phase: PHASE2
Conditions: Psoriasis
Sponsor: Bond Avillion 2 Development LP

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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
Page 3 of 103 
 
Table of Contents 
TABLE OF CONTENTS ........................................................................................................3 
1.0 
PROTOCOL SUMMARY ..........................................................................................7 
1.1 
Synopsis .............................................................................................................7 
1.2 
Schema ............................................................................................................19 
1.3 
Schedule of Activities (SoA) ..........................................................................20 
2.0 
INTRODUCTION......................................................................................................23 
2.1 
Study Rationale ..............................................................................................23 
2.2 
Background ....................................................................................................23 
2.3 
Benefit/Risk Assessment ................................................................................24 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................27 
4.0 
STUDY DESIGN ........................................................................................................29 
4.1 
Overall Design ................................................................................................29 
4.2 
Scientific Rationale for Study Design ...........................................................30 
4.3 
Justification for Dose .....................................................................................30 
4.4 
End of Study Definition .................................................................................31 
5.0 
STUDY POPULATION ............................................................................................32 
5.1 
Inclusion Criteria ...........................................................................................32 
5.2 
Exclusion Criteria ..........................................................................................32 
5.3 
Lifestyle Considerations ................................................................................37 
5.3.1 
Meals and Dietary Restrictions .........................................................37 
5.3.2 
Caffeine, Alcohol, Tobacco, and Cannabis/Marijuana .....................37 
5.3.3 
Activity ..............................................................................................37 
5.4 
Screen Failures ...............................................................................................37 
6.0 
STUDY DRUGS .........................................................................................................38 
6.1 
Study Drugs Administered ............................................................................38 
6.2 
Preparation/Handling/Storage/Accountability ...........................................39 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................40 
6.4 
Study Drug Compliance ................................................................................42 
6.5 
Previous and Concomitant Therapy, and Prohibited Medications ...........42 
6.5.1 
Rescue Medicine ...............................................................................43 
6.6 
Dose Modification ..........................................................................................43 
6.6.1 
Week 12 .............................................................................................43 
6.6.2 
Week 24 .............................................................................................44 
6.7 
Treatment after the End of the Study ..........................................................44 
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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
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7.0 
DISCONTINUATION OF STUDY DRUG AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ................................................................45 
7.1 
Discontinuation of Study Drug .....................................................................45 
7.1.1 
Temporary Discontinuation ...............................................................47 
7.1.2 
Rechallenge .......................................................................................47 
7.2 
Subject Withdrawal from the Study ............................................................47 
7.3 
Lost to Follow Up ...........................................................................................48 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................49 
8.1 
Study Procedures ...........................................................................................49 
8.1.1 
Screening ...........................................................................................49 
8.1.2 
Week 0 / Randomization ...................................................................51 
8.1.3 
Weeks 1, 3, 6, 10 ...............................................................................52 
8.1.4 
Week 2 ...............................................................................................52 
8.1.5 
Week 4 ...............................................................................................53 
8.1.6 
Weeks 8, 44, 52 .................................................................................54 
8.1.7 
Weeks 12, 24, 36, 48 .........................................................................55 
8.1.8 
Week 14 .............................................................................................56 
8.1.9 
Week 16, 20, 28, 32, 40 .....................................................................56 
8.1.10 
Unscheduled Visit .............................................................................57 
8.1.11 
Early Discontinuation ........................................................................57 
8.2 
Efficacy Assessments .....................................................................................59 
8.2.1 
Investigator’s Global Assessment (IGA mod 2011) .........................59 
8.2.2 
Assessment of Total Body Surface Area (BSA) and Psoriasis 
Area and Severity Index (PASI) ........................................................59 
8.3 
Quality of Life Instruments...........................................................................60 
8.3.1 
Dermatology Life Quality Index (DLQI) ..........................................60 
8.3.2 
Short-Form 36 (SF-36) ......................................................................60 
8.3.3 
Euro-Quality of Life Questionnaire for Psoriasis (EQ-PSO) ............60 
8.4 
Safety Assessments .........................................................................................61 
8.4.1 
Physical Examination ........................................................................61 
8.4.2 
Skin Evaluation .................................................................................61 
8.4.3 
Vital Signs .........................................................................................62 
8.4.4 
Electrocardiograms ............................................................................62 
8.4.5 
Clinical Safety Laboratory Assessments ...........................................63 
8.4.6 
Depression and Suicidal Risk Monitoring .........................................63 
8.4.6.1 
Electronic Self Rated Version, Columbia-Suicide 
Severity Rating Scale     (eC-SSRS) ................................64 
8.4.6.2 
Patient Health Questionnaire (PHQ-8) ............................64 
8.5 
Adverse Events (AEs) and Serious Adverse Events (SAEs).......................64 
8.5.1 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................65 
8.5.2 
Method of Detecting AEs and SAEs .................................................65 
8.5.3 
Follow-up of AEs and SAEs .............................................................65 
8.5.4 
Regulatory Reporting Requirements for SAEs .................................65 
8.5.5 
Pregnancy ..........................................................................................66 
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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
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8.5.6 
Cardiovascular and Death Events ......................................................66 
8.5.7 
Disease-Related Events and/or Disease-Related Outcomes 
Not Qualifying as AEs or SAEs ........................................................66 
8.6 
Overdose and Medication Errors .................................................................66 
8.7 
Pharmacokinetics ...........................................................................................67 
8.8 
Pharmacodynamics ........................................................................................67 
8.9 
Genetics ...........................................................................................................67 
8.10 
Biomarkers .....................................................................................................68 
8.10.1 
Immunogenicity Assessments ...........................................................68 
8.11 
Health Economics...........................................................................................68 
9.0 
STATISTICAL ANALYSIS .....................................................................................69 
9.1 
Statistical Hypotheses ....................................................................................69 
9.2 
Sample Size Determination ...........................................................................70 
9.3 
Populations for Analyses ...............................................................................70 
9.4 
Statistical Analyses.........................................................................................71 
9.4.1 
Efficacy Analyses ..............................................................................71 
9.4.2 
Subject Demographics/Other Baseline Characteristics .....................72 
9.4.3 
Subject Disposition ............................................................................72 
9.4.4 
Treatment Compliance ......................................................................72 
9.4.5 
Safety Analyses .................................................................................73 
9.4.5.1 
Vital Signs .......................................................................73 
9.4.5.2 
ECG Evaluations .............................................................73 
9.4.5.3 
Clinical Laboratory Evaluations ......................................73 
9.4.5.4 
Adverse Events ................................................................73 
9.4.5.5 
Suicidality and Self-Injurious Behavior ..........................73 
9.4.5.6 
Previous and Concomitant Therapy ................................74 
9.4.6 
Other Analyses ..................................................................................74 
9.4.7 
PK Analyses ......................................................................................74 
9.4.8 
Immunogenicity Analyses .................................................................74 
9.5 
Interim Analyses ............................................................................................74 
9.5.1 
Data Monitoring Committee (DMC) .................................................75 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS .................................................................................................76 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................76 
10.1.1 
Regulatory and Ethical Considerations .............................................76 
10.1.2 
Financial Disclosure ..........................................................................76 
10.1.3 
Informed Consent Process .................................................................76 
10.1.4 
Data Protection ..................................................................................77 
10.1.5 
Study Steering Committee .................................................................77 
10.1.6 
Dissemination of Clinical Study Data ...............................................77 
10.1.7 
Data Quality Assurance .....................................................................78 
10.1.8 
Source Documents .............................................................................78 
10.1.9 
Study and Site Closure ......................................................................78 
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AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
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10.1.10 Publication Policy ..............................................................................79 
10.2 
Appendix 2: Clinical Laboratory Tests........................................................80 
10.3 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................82 
10.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .....................................................................................................88 
10.5 
Appendix 5: HIV, Hepatitis B and Hepatitis C Virus Screening ..............91 
10.6 
Appendix 6: Measures of Psoriasis Area and Severity ...............................92 
10.6.1 
Investigator’s Global Assessment (IGA mod 2011) .........................92 
10.6.2 
Total Body Surface Area (BSA) and Psoriasis Area and 
Severity Index (PASI) .......................................................................93 
10.7 
Appendix 7: Abbreviations ...........................................................................96 
10.8 
Appendix 8: Protocol Amendment History .................................................98 
11.0 
REFERENCES .........................................................................................................101 
12.0 
SIGNATURE OF INVESTIGATOR .....................................................................103 
 
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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
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1.0 
PROTOCOL SUMMARY 
1.1 
Synopsis 
 
Name of Sponsor: 
Bond Avillion 2 Development LP 
Name of Finished 
Product: 
M1095 
Name of Active 
Ingredient: 
M1095 
Title of Study: 
 
A phase 2b randomized, double-blind, placebo controlled, multi-center 
12-week study with an additional 40-week follow-up assessment of 
efficacy, safety and tolerability of M1095 in subjects with moderate to 
severe chronic plaque-type psoriasis. 
Protocol No: 
 
AV002 
Co-ordinating 
Investigators: 
North America: 
 
 
Europe:
 
 
Study centers: 
Approximately 60 sites, in Europe and North America 
Study duration: 52 weeks 
Phase: 2b 
Objectives: 
Primary: 
• To evaluate the efficacy of four dose regimens of M1095 compared to placebo on 
achievement of an Investigator’s Global Assessment (IGA) score of 0 or 1 after 12 weeks of 
treatment in subjects with moderate to severe chronic plaque-type psoriasis. 
Secondary: 
• To evaluate the efficacy of four dose regimens of M1095 compared to placebo during a 12-
week treatment period on secondary endpoints: Psoriasis Area Severity Index (PASI) 75, 
PASI 90, PASI 100, change in PASI and shift in IGA. 
• To assess the dose-regimen efficacy relationship for M1095 after 12, 24, 36, and 48 weeks of 
treatment. 
• To evaluate the longer-term efficacy of M1095 at Week 24 and at Weeks 36 and 48. 
• To assess the safety and tolerability of M1095.  
 
 
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Exploratory: 
• Assessment of the quality of life and health outcomes of subjects treated with M1095 over 
48 weeks via quality of life instruments evaluated every 12 weeks. 
• Assessment of the population pharmacokinetics (PK) of various doses and dose regimens of 
M1095. 
• Assessment of the development of anti-drug antibodies for various doses and dose regimens 
of M1095. 
• Assessment of change in efficacy from Week 12 to Week 24 in subjects who undergo dose 
escalation. 
• Assessment of M1095 efficacy after being withheld in subjects with an IGA score of 0 at 
Week 24. 
Study Design:  
This is a multi-center phase 2b study in subjects with moderate to severe chronic plaque-type 
psoriasis. Approximately 300 subjects will be enrolled at approximately 60 investigator sites in North 
America and Europe. The study will consist of a 4-week screening period (Week -4 to Week 0), a 12 
week treatment period which is placebo-controlled (Week 0 to Week 12), a 12 week maintenance/ 
escalation period where all subjects are on active treatment (Week 12 to Week 24), a 24 week 
response assessment/dose hold period where active treatment is withheld if subjects being treated 
with M1095 have an IGA score of 0 at the beginning of the period (Week 24 to Week 48) and a final 
assessment period for safety follow up (Week 48 to Week 52). The study will be double-blind up to 
Week 24, with subject- and investigator-blind maintained throughout. 
Subjects will be randomized in a 1:1:1:1:1:1 ratio, with approximately 50 subjects randomized into 
each of six treatment groups as shown below and in Figure 1: 
1. Placebo wk 0, 1, 2, 3, 4, 6, 8, 10 / M1095 120mg wk 12, 14, 16 and q4w. 
2. M1095 30mg wk 0, 2, 4, 8, 12 and q4w.  
3. M1095 60mg wk 0, 2, 4, 8, 12 and q4w. 
4. M1095 120mg wk 0, 2, 4, 8, 12 and q8w. 
5. M1095 120mg wk 0, 2, 4, 6, 8, 10, 12 and q4w. 
6. Secukinumab 300mg wk 0, 1, 2, 3, 4, 8, 12 and q4w. 
Prior to Week 24: 
M1095 subjects in Arms 2 and 3 will receive placebo at Weeks 1, 3, 6, 10 and 14. 
M1095 subjects in Arm 4 will receive placebo at Weeks 1, 3, 6, 10, 14 and 16. 
M1095 subjects in Arm 5 will receive placebo at Weeks 1, 3 and 14. 
Secukinumab subjects in Arm 6 will receive placebo at Weeks 6, 10 and 14.  
Subjects randomized to 30mg or 60mg M1095 who do not achieve an IGA score of 0 or 1 at Week 
12 will be dose escalated to 120mg q4w starting at Week 12. 
Any subjects on M1095 who did not undergo dose escalation at Week 12 and who achieve an IGA 
score of 0 at Week 24 will have study drug withheld and will receive placebo q4w. Subsequently, if 
IGA score is 1 or more, these subjects will re-commence M1095 at the dose they received prior to  
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Week 24 on a q4w regimen at the visits scheduled by the protocol until the end of the treatment 
period. Dose will not be withheld for a second time, irrespective of subsequent IGA scores.  
Subjects receiving secukinumab will continue to receive 300mg q4w throughout the study. 
The subject blind will be maintained by the use of M1095 and matched placebo. The syringes used 
for all M1095 and placebo doses will be identical. All subjects will receive two injections of 1mL at 
each visit. There is also physical protection of the blind. Subjects will be asked to wear an eye-mask 
for all injections. 
Randomization will be stratified by prior biologic use (yes or no) and weight (≤90kg, >90kg). 
Figure 1 
Flow chart / design diagram 
The last study drug injection is at Week 44, with key safety and efficacy evaluations at Week 48 and 
final safety and efficacy assessments at Week 52. 
Planned number of 
subjects: 
300 
Diagnosis and 
main criteria for 
inclusion: 
Inclusion Criteria:  
1. Ambulatory male and female subjects between 18 and 75 years 
of age at time of consent. 
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2. Subject has had stable moderate to severe plaque-type psoriasis 
for at least 6 months prior to randomization (e.g., no morphology 
changes or significant flares of disease activity in the opinion of 
the investigator). 
3. Subject must be considered, in the opinion of the investigator, not 
adequately controlled by photo, topical or previous systemic 
treatments and a candidate for systemic biologic therapy. 
4. Subject has IGA ≥3, involved body surface area (BSA) ≥10%, 
and PASI ≥12 at screening and at baseline. 
5. Subject is in the opinion of the investigator able to comply with 
the study procedures. 
6. Following verbal and written information about the study, subject 
must provide signed and dated informed consent before any study 
related activity is carried out. 
Exclusion Criteria:  
1. Subject diagnosed with erythrodermic psoriasis, pustular 
psoriasis, guttate psoriasis, or other skin conditions at the time of 
the screening visit (e.g., eczema) that would interfere with 
evaluations of psoriasis (Note: psoriatic arthritis is NOT 
exclusionary). 
2. Subject has drug-induced psoriasis (i.e. new onset or current 
exacerbation from beta-blockers, calcium channel inhibitors or 
lithium). 
3. Other medical conditions: 
a. At the time of consent, subject has a planned in-patient 
surgical intervention between baseline and the Week 52 
evaluation. 
b. Subject has an active infection or history of infections as 
follows: 
i. Any active infection for which systemic anti-
infectives were used within 28 days prior to 
randomization. 
ii. A serious infection, defined as requiring 
hospitalization or intravenous anti-infectives 
within 8 weeks prior to randomization. 
iii. Any history of bone infection requiring surgical 
intervention and/or intravenous antibiotics. 
iv. Recurrent or chronic infections or other active 
infection that, in the opinion of the investigator, 
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might cause this study to be detrimental to the 
subject. 
c. Subject has active tuberculosis. 
d. Subject has a positive QuantiFERON®-TB Gold test for 
tuberculosis at screening, or the first test and a repeat test 
are both indeterminate, unless (i) subject has a known 
history of latent TB and has completed a course of 
treatment or (ii) subject has received sufficient treatment 
for latent TB to allow concomitant treatment with a 
biological therapy as per local guidelines (note these 
subjects must continue their concomitant latent TB 
treatment to completion while participating in the study). 
If these subjects are outside of the screening window (>28 
days since consent) when they become eligible to 
participate, they should be fully re-screened for the study.  
e. Subject has an underlying condition (including, but not 
limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or 
gastrointestinal) which in the opinion of the investigator 
places the subject at unacceptable risk for receiving an 
immunomodulatory therapy. 
f. Subject has known history of inflammatory bowel 
disease. 
g. Subject with known chronic liver disease or tests positive 
for hepatitis B virus (HBV) infection or has antibodies to 
hepatitis C virus (HCV) at screening (see Section 10.5, 
Appendix 5 in the protocol main text). 
h. Subject has antibodies to human immunodeficiency 
virus (HIV) at screening (see Section 10.5, Appendix 5 
in the protocol main text). 
i. Subject has history of heart failure, myocardial infarction 
or unstable angina pectoris within the 12 months prior to 
randomization. 
j. Subject has uncontrolled hypertension characterized by 
two blood pressure measurements separated by at least 15 
minutes 
with 
systolic 
>160mmHg 
or 
diastolic 
>100mmHg. 
k. Subject has clinically significant electrocardiogram 
(ECG) abnormalities on centrally read ECG. 
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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
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l. Subject has any active malignancy, including evidence of 
cutaneous basal or squamous cell carcinoma or 
melanoma. 
m. Subject has history of malignancy within 5 years 
EXCEPT cutaneous squamous or basal cell carcinoma, in 
situ cervical cancer, or in situ breast ductal carcinoma 
which has been treated and considered cured. 
n. Subject has any concurrent medical condition that, in the 
opinion of the investigator, could cause this study to be 
detrimental to the subject. 
4. Subject has laboratory abnormalities at screening, including any 
of the following: 
a. Aspartate 
aminotransferase 
(AST) 
or 
alanine 
aminotransferase (ALT) >2 x the upper limit of normal 
(one 
retest 
is 
allowed 
for 
aminotransferase 
abnormalities). 
b. Serum direct bilirubin >1.5 mg/dL. 
c. White blood cell (WBC) count <3.00 x 103/µL. 
d. Absolute neutrophil count <1.50 x 103/µL. 
e. Absolute lymphocyte count <0.50 x 103/µL. 
f. Platelet count <100,000/µL. 
g. Creatinine clearance of <30mL/min (calculated via 
Cockcroft Gault).     A subsequent 24-hour urine 
collection may be performed with the prior approval of 
the Medical Monitor, and if via urine collection the 
creatinine clearance is >30mL/min the subject is eligible 
for the study.    
AMENDMENT FOR CZECH REPUBLIC               
Creatinine clearance of <60 mL/min (calculated via 
Cockcroft Gault). A subsequent 24-hour urine collection 
may be performed with the prior approval of the Medical 
Monitor, and if via urine collection the creatinine 
clearance is >60mL/min the subject is eligible for the 
study.   
h. Any other laboratory abnormality, which, in the opinion 
of the investigator, will prevent the subject from 
completing the study or will interfere with the 
interpretation of the study results. 
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5. Subject has used topical therapy as follows: 
a. Topical psoriasis treatment within 14 days of 
randomization, 
including, 
but 
not 
limited 
to, 
corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, topical calcineurin inhibitors, retinoids, 
tazarotene, as well as emollients and other non-
prescription topical products that contain urea, >3% 
salicylic acid, or alpha- or beta-hydroxyl acids, and 
medicated shampoos (e.g. those that contain >3% 
salicylic acid, corticosteroids, coal tar, or vitamin D3 
analogues). 
Exceptions: mild/least potent topical steroids are 
permitted during screening for use limited to the face, 
axillae, and/or genitalia but must be discontinued 24 
hours prior to the baseline visit (randomization). 
b. Bland emollients (without alpha or beta hydroxy acids) 
within 24 hours of baseline visit (randomization). Note 
that as per Section 6.5 bland emollients (without alpha 
or beta hydroxy acids) may be used during the study 
but MAY NOT be used within 24 hours prior to any 
study visit. 
6. Subject has used the following within 28 days of randomization: 
ultraviolet A (UVA) light therapy (with or without psoralen); 
ultraviolet B (UVB) light therapy; excimer laser; oral retinoids; 
methotrexate; 
cyclosporine; 
systemically 
administered 
calcineurin inhibitors; azathioprine; thioguanine; hydroxyurea; 
cyclophosphamide; fumarates; apremilast; or oral or parenteral 
corticosteroids 
including 
intramuscular 
or 
intraarticular 
administration (exception: otic, nasal, ophthalmic, or inhaled 
corticosteroids within recommended doses is permitted); other 
non-biologic systemic therapy for psoriasis. 
7. Subject is not willing to limit ultraviolet (UV) light exposure (e.g. 
sunbathing and/or the use of tanning devices) during the study. 
8. Subject has received live vaccine(s) within 6 weeks of 
randomization. 
9. Subject has received prior treatment at any time before screening 
with any compound (marketed or investigational) targeting IL-17 
(i.e. direct inhibitor, receptor blocker, etc.). 
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10. Subject has received prior treatment at any time before screening 
with more than 2 biologic therapies (ustekinumab, tumour 
necrosis factor (TNF) targeting therapies, or investigational 
therapies).  
11. Subject has received TNF targeting therapies in the 12 weeks 
prior to randomization, ustekinumab in the 6 months prior to 
randomization, or investigational biological therapies within 12 
weeks, or 5 half lives of randomization, whichever is the longer. 
12. Subject has known sensitivity to any of the products or 
components to be administered during dosing. 
13. Subject has a history or evidence of suicidal ideation or behavior 
within the 12 months prior to randomization or evidence of severe 
depression at screening or baseline [i.e. severity level 3, 4 or 5 
based on an assessment with the electronic Columbia Suicide 
Severity Rating Scale (eC-SSRS)]. 
14. Subject has a history of chronic alcohol abuse or  chronic drug 
abuse, or has used intravenous (IV) drugs in the past 2 years. 
15. Women of child bearing potential who are not willing to use 
highly effective methods of birth control during treatment and for 
12 weeks after the last dose of study drug. See Section 10.4, 
Appendix 4 in the main protocol text for the definition of child 
bearing potential and guidance on highly effective methods of 
birth control. 
16. Subject has a positive serum pregnancy test during screening or 
a positive urine pregnancy test at baseline (Week 0, 
randomization visit), except those surgically sterile or at least 1 
year postmenopausal.  
17. Subject is pregnant or breast feeding, or planning to become 
pregnant while enrolled in the study and for 12 weeks after the 
last dose of study drug. 
18. Male subjects who are not willing to use contraception during 
treatment and for 12 weeks after the last dose of study drug. See 
Section 10.4, Appendix 4 for definition of permitted methods of 
contraception in male subjects.  
19. Subject will not be available for protocol required study visits or 
procedures, (e.g. venepuncture) to the best of the subject's and 
investigator's knowledge. 
20. Subject has any kind of disorder that, in the opinion of the 
investigator, may compromise the ability of the subject to give 
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informed consent and/or to comply with all required study 
procedures. 
21. Subject is either 
a. Currently 
enrolled 
in 
another 
interventional, 
investigational device or drug study. 
b. Has been in another investigational device or drug 
study(s) in the 30 days prior to consent. 
22. Subject or subject’s immediate family is an employee of the study 
sponsor (Bond Avillion 2 Development LP), Avillion LLP, EMD 
Serono, Merck KGaA or any contract research organization 
(CRO) associated with the study.  
23. Subject or subject’s immediate family is working for or employed 
by the investigator. 
Reference therapy, 
dose, and mode of 
administration: 
1. Placebo, in 2 x 1mL subcutaneous injections, given at Week 0, 1, 2, 
3, 4, 6, 8 and 10. (These subjects will then receive study drug: 
M1095, 120mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study 
drug, 1mL placebo, given at Week 12, 14, 16, and q4w). 
Active therapy, dose 
and mode of 
administration: 
2.  M1095, 30 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study 
     drug, 1mL placebo, given at Week 0, 2, 4, 8, 12 and q4w.  
     (These subjects will also receive placebo, in 2 x 1mL subcutaneous  
     injections, at Week 1, 3, 6, 10 and 14). 
3.  M1095, 60 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study  
     drug, 1mL placebo, given at Week 0, 2, 4, 8, 12 and q4w.  
     (These subjects will also receive placebo, in 2 x 1mL subcutaneous  
     injections, at Week 1, 3, 6, 10 and 14). 
4.  M1095, 120 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study  
     drug, 1mL placebo, given at Week 0, 2, 4, 8, 12 and q8w.  
     (These subjects will also receive placebo, in 2 x 1mL subcutaneous  
     injections, at Week 1, 3, 6, 10, 14, 16, 24, 32 and 40). 
5.  M1095, 120 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study  
     drug, 1mL placebo, given at Week 0, 2, 4, 6, 8, 10, 12 and q4w.  
     (These subjects will also receive placebo, in 2 x 1mL subcutaneous  
     injections, at Week 1, 3 and 14).  
6.  Secukinumab, 300mg, in 2 x 1mL (150mg/mL) subcutaneous 
     injections, given at Week 0, 1, 2, 3, 4, 8, 12 and q4w.  
     (These subjects will also receive placebo, in 2 x 1mL subcutaneous  
     injections, at Week 6, 10 and 14). 
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The 30mg and 60mg M1095 doses (in arms 2 and 3) will be escalated at 
Week 12 in subjects who have not achieved an IGA score of 0 or 1, as 
described in Section 6.6.1.  
M1095 doses (in arms 1 to 5) may be replaced by placebo at Week 24 as 
described in Section 6.6.2 of the main protocol text.  
Criteria for evaluation: 
Primary Endpoint: 
• IGA score of 0 or 1 at Week 12, with an IGA reduction of at least 2 points from baseline. 
Secondary Endpoints:  
• Efficacy: 
o PASI 75 at Week 12. 
o PASI 90 at Week 12. 
o PASI 100 at Week 12. 
o PASI 75, PASI 90 and PASI 100 beyond Week 12. 
o Change from baseline in PASI score and in total BSA affected by plaque-type 
psoriasis. 
o Shift from baseline in IGA score category. 
• Safety: Adverse events, skin evaluation, laboratory assessments, vital signs, ECGs, drug 
discontinuations, and instruments to assess depression and suicidality [electronic Columbia-
Suicide Severity Rating Scale (eC-SSRS) and Personal Health Questionnaire Depression 
Scale (PHQ-8)]. 
Exploratory Endpoints: 
• Dermatology Life Quality Index (DLQI), Short Form 36 (SF-36) and Euro-Quality of Life 
Questionnaire for Psoriasis (EQ-PSO). 
• Population PK evaluation. 
• Anti-drug antibodies: determination of binding and neutralizing antibodies defined by 
percentage of subjects with antibodies and titers of antibody. 
• Monitoring of pre-existing antibodies against M1095. 
• IGA and PASI endpoints in subjects who dose escalate to 120mg M1095 q4w at Week 12. 
• IGA and PASI endpoints in subjects with an IGA score of 0 for whom M1095 is withheld at 
Week 24. 
 
Statistical Methods 
Sample size: 
A total of approximately 300 subjects will be randomized, approximately 50 per treatment group. 
With this sample size, the study has >99% power to detect a statistically significant difference 
between any treatment arm and placebo in the IGA score of 0 or 1 responder rate at Week 12, with a 
two-sided, unadjusted type I error of 0.05. These calculations assume IGA score of 0 or 1 rates of 
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>88% for study drug and ≤7% for placebo. As this is a phase 2 study, there will be no adjustments 
for multiplicity.  
Exploratory analyses between the different dose regimens of M1095 will also be performed. The 
PASI 100 response rate offers more discriminatory potential for this. Phase 1 data and response 
simulations give a PASI 100 response rate at Week 12 varying from 45 to 72%. With the sample size 
of approximately 50 subjects per group, based on these assumed PASI 100 response rates at Week 
12, the comparison between the highest and lowest M1095 doses has approximately 79% power. 
Analysis sets: 
The Intent to Treat (ITT) population includes all subjects randomly allocated to a treatment. The 
Modified Intent to Treat (MITT) population includes all subjects in the ITT Analysis Set who receive 
at least one dose of study drug, have a baseline, and at least one post baseline efficacy assessments. 
The Per-Protocol (PP) population includes all subjects in the MITT Analysis Set who have no 
important protocol deviations affecting the assessment of efficacy. Membership of the PP Analysis 
Set will be confirmed prior to unblinding the data. The ITT, MITT and PP populations will be 
analyzed per planned treatment.  
The Safety population is all subjects who receive at least one dose of study treatment. The Safety 
population will be analyzed per the actual treatment received. 
Primary analysis: 
The primary endpoint is achievement of an IGA score of 0 or 1 at 12 weeks. The response rate for 
the IGA score of 0 or 1 at Week 12 is defined as the proportion of subjects at Week 12 with an IGA 
score of 0 or 1 and with a reduction from baseline IGA of 2 points or more. Baseline IGA score is 
the last score prior to the first dose of study medication. Any missing IGA score of 0 or 1 response 
will be imputed as a non-response. 
The primary analysis will be based on the ITT Analysis Set. The primary treatment comparisons will 
be made using the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by prior biologic use 
(yes/no) and body weight stratum (≤90kg, >90kg.) 
Sensitivity analyses: 
The primary analysis will be repeated on the MITT and PP Analysis Sets. Furthermore, selected 
sensitivity analyses will be performed on the ITT Analysis Set, including multiple imputation and 
last-observation carried forward. 
Secondary analyses: 
Secondary efficacy and QoL endpoints will be compared between treatments at each visit up to Week 
48 using the CMH test for binary endpoints and an Analysis of Covariance (ANCOVA) model for 
changes from baseline.  
Safety data will be summarized in the Safety Analysis Set by treatment and over time, for each 
treatment period separately and overall. 
 
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Exploratory analyses: 
Exploratory analyses of efficacy will be made for (i) all subjects who were dose-escalated at Week 
12, and (ii) all subjects who had active treatment withheld following an IGA score of 0 at Week 24. 
Subgroup analyses: 
Subgroup analyses of key efficacy and safety data will be performed as appropriate by geographical 
region, prior biological use, weight category, gender and geriatric status. 
Interim analyses: 
An independent Data Monitoring Committee (DMC) will be established to perform and review 
interim analyses during the study. The DMC will be operational prior to enrolment of the first subject 
into the study. The composition and operation of the DMC will be described in a DMC charter. The 
charter will also detail how the communication between the DMC and the sponsor will be firewalled 
to preserve the blinding and integrity of the study.  
The DMC will closely monitor the safety and tolerability data throughout the trial. No formal analysis 
of efficacy is planned during the double-blind, placebo-controlled 12-week induction phase. 
An unblinded interim analysis of 12-week data will occur at the completion of the Week 12 period, 
while the study is still ongoing. These data will be shared with firewalled individuals who are not 
directly involved in the conduct of the study.  
A second interim analysis will occur at the completion of the Week 24 period. All investigators and 
subjects will remain blinded to treatment assignments until the last subject completes the study and 
the final database lock occurs. Once the second interim database lock has occurred after Week 24, 
the sponsor study team will be unblinded.  
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1.2 
Schema 
 
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E. If a urine pregnancy test is positive, study treatment must be withheld. A serum pregnancy test (central) should be performed. See Section 10.4, 
Appendix 4 for details.  
F. Quantiferon TB test must be study specific and can be performed either by the central or local laboratory. If a Quantiferon TB test result is 
‘indeterminate’ the test must be repeated during the Screening period. If any Quantiferon TB test is ‘positive’ or if the first test and the repeat test are 
both ‘indeterminate’, the subject must be referred for tuberculosis workup per local guidelines. The subject is eligible for randomization if (i) they have 
a known history of latent TB and have completed a course of treatment or (ii) they have received sufficient treatment for latent TB to allow concomitant 
treatment with a biological therapy as per local guidelines (note these subjects must continue their concomitant latent TB treatment to completion while 
participating in the study, and if these subjects are outside of the screening window (>28 days since consent) when they become eligible to participate, 
they should be fully re-screened for the study). The subject is not eligible for randomization if either ‘active tuberculosis is present’ or if ‘latent 
tuberculosis is present and is untreated per local guidelines.’  
G. Subjects that test positive for anti-drug antibodies at the last study visit (either Week 52 or Early Discontinuation) may be requested to provide another 
sample approximately 6 to 12 months after study completion. 
H. Patient Reported Outcomes should be conducted at the start of each visit, before other assessments. 
I. 
Chest X-ray within 3 months of consent is considered acceptable. When performed as part of the Screening visit, the chest X-ray should be the last study 
procedure to be completed, as this will prevent unnecessary exposure to radiation if the subject is found to be ineligible following an earlier procedure. 
Investigator should follow up the results of the chest X-ray with the Medical Monitor if clinically indicated. 
J. 
Subjects randomized to M1095 30mg or 60mg who do not achieve an IGA score of 0 or 1 at Week 12 will be dose escalated to 120mg q4w. All study 
drug is allocated via IRT. 
K. Any subjects randomized to M1095 who did not undergo dose escalation at Week 12 and who achieve an IGA score of 0 at Week 24 will have study drug 
withheld and will receive placebo q4w. Subsequently, if IGA score is 1 or more, these subjects will re-commence M1095 at the dose they received prior 
to Week 24 on a q4w regimen at the visits scheduled by the protocol until the end of the treatment period. Dose will not be withheld for a second time, 
irrespective of subsequent IGA scores. All study drug is allocated via the IRT.  
L. The investigator should carefully consider the subject’s response at Week 24 and if there has been a worsening of psoriasis compared to baseline then the 
investigator should consider discontinuing the subject from the study if they are not receiving adequate benefit from their participation. 
 
 
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2.0 
INTRODUCTION 
M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and 
IL-17A/F. A strong scientific and medical rationale exists for the use of M1095 in the treatment 
of autoimmune disease, including psoriasis.  
2.1 
Study Rationale  
Despite several biologic treatment options, the development of new psoriasis therapies is 
important. M1095 is a viable investigational treatment of psoriasis with the potential for a 
similar or improved risk/benefit profile compared to available therapies. This is a phase 2b 
study to evaluate the safety and efficacy of M1095 for the treatment of moderate to severe 
plaque-type psoriasis. 
2.2 
Background 
Psoriasis is a skin condition estimated to affect about 2-4% of the population in western 
countries with a higher prevalence in Caucasians and approximately equal frequency in males 
and females.1 The most common form is psoriasis vulgaris (plaque-type psoriasis) which is 
characterized by lesions which often itch and burn and manifest as raised, inflamed, red skin 
covered with silvery, white scales. The disease can appear anywhere although it is most 
common on extensor surfaces such as elbows and knees, plus the scalp and lower back. Mild 
severity disease can often be managed with topical treatments. As the disease severity 
increases, phototherapy or systemic therapies such as retinoids, methotrexate, cyclosporine, 
apremilast, or biologic immune modifying agents are required for disease control.  
The understanding of the pathophysiology behind psoriatic plaques has expanded markedly 
during the past twenty years leading to an expansion in the armamentarium for disease 
treatment. Cytokines which are known to play a role in psoriasis include, but are not limited 
to, TNF-α, IL-12, IL-23, and IL-17.2 Since 2004, several biologic therapies targeting these 
cytokines have been developed and approved for the treatment of moderate to severe psoriasis. 
The first therapy targeting TNF-α was approved in 2004, a therapy targeting IL-12/IL-23 was 
approved in 2009, the first therapy targeting IL-17 was approved in 2015, and a therapy 
targeting only IL-23 was approved in 2017. While these therapies have significantly improved 
on prior treatments there are still significant unmet needs in psoriasis which drive continued 
development of new therapies. 
IL-17 is a known target for psoriasis treatment and three drugs that target this mechanism are 
currently available. Secukinumab is a human immunoglobulin G1 (IgG1) monoclonal antibody 
that selectively binds IL-17A, ixekizumab is a humanized IgG4 monoclonal antibody that 
selectively binds IL-17A, and brodalumab is a human monoclonal IgG2 antibody that 
selectively binds to the IL-17 receptor inhibiting interactions with IL-17A, IL-17F, IL-17C, 
IL-17A/F and IL-25.3  
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M1095 differs from the approved therapies in several important ways which could provide a 
therapeutic advantage. First, it is a nanobody vs. an antibody. Nanobodies are a novel class of 
proteins that are based on single-domain antibody fragments and therefore are smaller and 
more robust than conventional antibodies.4 Second, M1095 specifically targets IL-17A and IL-
17F. Secukinumab and ixekizumab only interact with IL-17A and it has been reported that IL-
17F also plays a role in psoriasis pathophysiology. Brodalumab does target both IL-17A and 
IL-17F; however, it also blocks the IL-17 receptor from interacting with several other 
cytokines (IL-17C and IL-25) which may account for additional untoward effects that are not 
related to its ability to treat psoriasis. 
M1095 has been evaluated in subjects with psoriasis in study EMR200574-003, “A 
Multicenter, Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the 
Safety, Tolerability, Immunogenicity, Pharmacokinetics, Pharmacodynamics and Efficacy of 
Multiple Ascending Doses of Subcutaneous M1095 (Anti-IL17A/F Nanobody) in Male and 
Female Subjects with Moderate to Severe Psoriasis.” The phase 1 study demonstrated that 
M1095 was generally well tolerated with robust efficacy and a pharmacokinetic (PK) profile 
suitable for long-term dosing on a 4 weekly or 8 weekly schedule. Furthermore, the efficacy 
results were suggestive that M1095 at the proposed doses may be able to deliver an 
improvement in Psoriasis Area and Severity Index (PASI) 90 and PASI 100 responses 
compared to what has been described with currently approved IL-17 modulating therapies. A 
full description of the results for this study can be found in the Investigator’s Brochure. 
2.3 
Benefit/Risk Assessment 
Despite several biologic treatment options, new psoriasis therapies are needed. M1095 is a 
viable candidate treatment with the potential for a similar or improved risk/benefit profile 
compared to available therapies. All subjects in this study will receive M1095 or secukinumab 
as those randomized to placebo will switch to M1095 at Week 12. 
In EMR200574-003, subjects received three doses of M1095 at 2-week intervals over one 
month. Dose levels of 30mg through 240mg were tested. The study demonstrated that  
• M1095 administered up to a dose of 240mg q2w x 3 was generally well tolerated in a 
group of 33 subjects with moderate to severe psoriasis. 
• AUC and Cmax were dose proportional from 30mg to 240mg with a terminal half life 
of 11-12 days. 
• A dose-response relationship was observed with PASI 75/90/100 responses.  
The most common AEs (occurring in 2 or more of the 33 subjects treated with M1095) were 
pruritus, headache, hypertension, nasopharyngitis, somnolence and bronchitis. Two subjects 
discontinued due to AEs (an injection site reaction in a subject receiving 120mg and an 
elevation in aminotransferases in a subject receiving 240mg) and one SAE occurred (acute 
vestibular syndrome, in a subject receiving 30mg, which was deemed unrelated to study drug).  
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Subjects in the study were between 18 and 70 years old with moderate to severe psoriasis of at 
least 6 months duration, a static Physician’s Global Assessment (sPGA) of ≥3, ≥10% body 
surface area and a PASI score of ≥12. PASI 75/90/100 responses at Week 12 (8 weeks after 
the last M1095 injection) ranged from 88%/50%/13% to 100%/100%/56%. Achievement of 
sPGA scores of 0 and 1 at week 12 ranged from 88% to 100%. A full description of the safety 
and efficacy data from this study can be found in the Investigator’s Brochure. 
 
Secukinumab is an IL-17 antagonist that was approved by the Food and Drug Administration 
(FDA) and European Medicines Agency (EMA) in 2015 and is indicated for moderate to 
severe plaque-type psoriasis in adult subjects who are candidates for systemic therapy or 
phototherapy, the same population that will be enrolled in this study. The most common 
adverse reactions (>1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection. 
Warnings and precautions include infections, tuberculosis, inflammatory bowel disease, and 
hypersensitivity reactions. In the pivotal phase 3 studies ERASURE (Efficacy of Response and 
Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year 
Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to 
Determine Efficacy in Psoriasis), at the 300mg secukinumab dose PASI 75 responses ranged 
from 76 to 82% and PASI 90 responses ranged from 54 to 59%.5 A full description of the safety 
and efficacy data for secukinumab can be found in the Prescribing Information6 or Summary 
of Product Characteristics (SmPC).7 
All subjects in this 52-week study will receive active therapy, 1/6 will be exposed to placebo 
for 12 weeks followed by M1095, 4/6 will be randomized to M1095 from the outset and 1/6 
will receive secukinumab at the approved dose. Based on currently available data subjects 
should experience some improvement in their psoriasis with either M1095 or secukinumab. Of 
note, subjects on the lower doses of M1095 who do not achieve an IGA score of 0 or 1 at Week 
12 will be increased to the highest dose.  
The most likely predicted AEs based on the clinical studies conducted to date are infections, 
injection site reactions, and gastrointestinal upset. Less common, but more severe AEs which 
have been reported with other IL-17 modulating agents such as hypersensitivity reactions, 
more severe infections, and suicidality will be managed via inclusion/exclusion criteria, careful 
and frequent monitoring, and administration of all study drug in the clinic.  
In cynomolgus monkeys, non-clinical toxicology studies lasting 26-weeks and 39-weeks 
minimal to mild reddish discoloration of the skin in the axillary and inguinal regions, 
associated with a histopathological diagnosis of superficial perivascular dermatitis, was 
observed. These findings improved but did not completely recover during the recovery period 
in these studies. The overall risk associated with these findings in human study subjects is low. 
If similar findings occur they will be observable on skin evaluation and managed appropriately.  
Subjects will be followed closely (weekly during the first month, biweekly for the second and 
third month and then at least monthly for the remainder of the study) and observed via standard 
assessments including queries about AEs, periodic examinations, and laboratory assessments. 
Subjects who experience notable study drug related AEs or lab abnormalities will be 
discontinued (see Section 7.1).  
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In addition to the assessment of an individual’s benefit-risk there will be an independent Data 
Monitoring Committee (DMC) that will evaluate study data periodically to ensure there are no 
new risks that emerge from the accumulating data. 
 
 
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3.0 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
• To evaluate the efficacy of four dose 
regimens of M1095 compared to placebo 
on achievement of an IGA score of 0 or 1 
after 12 weeks of treatment in subjects 
with moderate to severe chronic plaque-
type psoriasis. 
• IGA score of 0 or 1 at Week 12, with an 
IGA reduction from baseline of at least 2 
points. 
 
Secondary 
• To evaluate the efficacy of M1095 
compared to placebo during a 12-week 
treatment period on secondary endpoints: 
PASI 75, PASI 90, PASI 100, change in 
PASI and shift in IGA. 
• To assess the dose-regimen efficacy 
relationship for M1095 after 12, 24, 36, 
and 48 weeks of treatment. 
• To evaluate the longer-term efficacy of 
M1095 at Week 24 and at Weeks 36 and 
48.  
• To assess the safety and tolerability of 
M1095. 
 
• Efficacy: 
• PASI 75 at Week 12. 
• PASI 90 at Week 12. 
• PASI 100 at Week 12. 
• PASI 75, PASI 90 and PASI 100 
beyond Week 12. 
• Change from baseline in PASI score and 
in total BSA affected by plaque-type 
psoriasis. 
• Shift from baseline in IGA score 
category. 
• Safety:  
• Adverse events, skin evaluation, 
laboratory assessments, vital signs, 
ECGs, drug discontinuations, and 
instruments to assess depression and 
suicidality [electronic Columbia-Suicide 
Severity Rating Scale (eC-SSRS) and 
Personal Health Questionnaire 
Depression Scale (PHQ-8)]. 
Exploratory 
• Assessment of the quality of life and 
health outcomes of subjects treated with 
M1095 over 48 weeks via quality of life 
instruments evaluated every 12 weeks. 
• Assessment of the population PK of 
various doses and dose regimens of 
M1095. 
• Assessment of the development of anti-
drug antibodies for various doses and 
dose regimens of M1095. 
• Dermatology Life Quality Index (DLQI), 
Short Form 36 (SF-36), and EuroQuality of 
Life Questionnaire for Psoriasis (EQ-PSO). 
• Population PK evaluation. 
• Anti-drug antibodies: determination of 
binding and neutralizing antibodies defined 
by percentage of subjects with antibodies 
and titers of antibody. 
• Monitoring of pre-existing antibodies 
against M1095. 
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Objectives 
Endpoints 
• Assessment of change in efficacy from 
Week 12 to Week 24 in subjects who 
undergo dose escalation. 
• Assessment of M1095 being withheld in 
subjects with an IGA score of 0 at Week 
24. 
• IGA and PASI endpoints in subjects who 
dose escalate to 120mg M1095 q4w at 
Week 12. 
• IGA and PASI endpoints in subjects with 
an IGA score at 0 for whom M1095 is 
withheld at Week 24. 
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4.0 
STUDY DESIGN 
4.1 
Overall Design 
This is a multi-center phase 2b study in subjects with moderate to severe chronic plaque-type 
psoriasis. Approximately 300 subjects will be enrolled at approximately 60 investigator sites 
in North America and Europe. The study will consist of a 4-week screening period (Week -4 
to Week 0), a 12 week treatment period which is placebo-controlled (Week 0 to Week 12), a 
12 week maintenance/escalation period where all subjects are on active treatment (Week 12 to 
Week 24), a 24 week response assessment/dose hold period where active treatment is withheld 
if subjects being treated with M1095 have an IGA score of 0 at the beginning of the period 
(Week 24 to Week 48) and a final assessment period for safety follow up (Week 48 to Week 
52). The study will be double-blind up to Week 24, with subject- and investigator-blind 
maintained throughout.  
Subjects will be randomized in a 1:1:1:1:1:1 ratio, with approximately 50 subjects randomized 
into each of six treatment groups as shown below and in Figure 1: 
1. Placebo wk 0, 1, 2, 3, 4, 6, 8, 10 / M1095 120mg wk 12, 14, 16 and q4w. 
2. M1095 30mg wk 0, 2, 4, 8, 12 and q4w.  
3. M1095 60mg wk 0, 2, 4, 8, 12 and q4w. 
4. M1095 120mg wk 0, 2, 4, 8, 12 and q8w. 
5. M1095 120mg wk 0, 2, 4, 6, 8, 10, 12 and q4w. 
6. Secukinumab 300mg wk 0, 1, 2, 3, 4, 8, 12 and q4w. 
Prior to Week 24: 
M1095 subjects in Arms 2 and 3 will receive placebo at Weeks 1, 3, 6, 10 and 14. 
M1095 subjects in Arm 4 will receive placebo at Weeks 1, 3, 6, 10, 14 and 16. 
M1095 subjects in Arm 5 will receive placebo at Weeks 1, 3 and 14. 
Secukinumab subjects in Arm 6 will receive placebo at Weeks 6, 10 and 14.  
Subjects randomized to 30mg or 60mg M1095 who do not achieve an IGA score of 0 or 1 at 
Week 12 will be dose escalated to 120mg q4w starting at Week 12. 
Any subjects randomized to M1095 who did not undergo dose escalation at Week 12 and who 
achieve an IGA score of 0 at Week 24 will have study drug withheld and will receive placebo 
q4w. Subsequently, if IGA score is 1 or more, these subjects will re-commence M1095 at the 
dose they received prior to Week 24 on a q4w regimen at the visits scheduled by the protocol 
until the end of the treatment period. Dose will not be withheld for a second time, irrespective 
of subsequent IGA scores.  
Subjects receiving secukinumab will continue to receive 300mg q4w throughout the study. 
The subject blind will be maintained by the use of M1095 and matched placebo. The syringes 
used for all M1095 and placebo doses will be identical. All subjects will receive two injections 
of 1mL at each visit. There is also physical protection of the blind. Subjects will be asked to 
wear an eye-mask for all injections. 
Randomization will be stratified by prior biologic use (yes or no) and weight (≤90kg, >90kg). 
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4.2 
Scientific Rationale for Study Design 
The study design is similar to that utilized by several biologics in psoriasis for phase 2 and 
phase 3 studies. The evaluation of M1095 versus placebo at Week 12 is consistent with 
regulatory precedents and guidance.8 The overall duration of 52 weeks will enable assessment 
of long term efficacy and safety as well as the effect of treatment withdrawal in subjects with 
an IGA score of 0. All subjects will be eligible for at least 36 weeks of active therapy with 
placebo subjects converting from placebo to M1095 at Week 12.  
As described in the background and thoroughly covered in the Investigator’s Brochure, IL-17 
is a validated target in psoriasis. Furthermore, proof of concept has been obtained via the phase 
1 multiple dose study in subjects with psoriasis. Secukinumab is an approved drug that also 
targets IL-17. 
Inclusion and exclusion criteria described in Sections 5.1 and 5.2 have been developed to 
ensure a well-defined population where efficacy can be determined without introducing any 
unacceptable risks. The study design incorporates frequent visits and evaluations to optimize 
assessment of endpoints and collection of safety data. 
4.3 
Justification for Dose 
The M1095 doses selected for the study (30mg, 60mg, 120mg) are based on the results from 
the phase 1 multiple dose study EMR200574-003 in subjects with moderate to severe psoriasis 
(Figure 2). All doses in study EMR200574-003 showed efficacy based on PASI response, 
however, the lowest dose of 30 mg was less efficacious than the highest dose planned for this 
study, 120mg. This suggests that the doses selected are differentiated and will allow an 
understanding of the dose/exposure response relationship. It is notable that the dosing regimen 
employed in the phase 1 study was administered at Week 0, 2, and 4 followed by endpoint 
evaluation at Week 12. 
In the current phase 2b study, q2w, q4w and q8w regimens will be evaluated. Simulations 
using the efficacy-exposure data from phase 1 suggest that PASI 100 scores at Week 12 will 
vary between approximately 45% to 60% in subjects receiving 30mg M1095 administered at 
Week 0, 2, 4, 8 and 12, and 72% to 85% in subjects receiving 120mg M1095 administered at 
Week 0, 2, 4, 6, 8, 10 and 12. While comparison between each treatment arm will not 
necessarily reveal statistically significant differences, exploratory comparisons between the 
various dose arms will enable exploration of several questions: (1) does the amount of drug 
significantly affect Week 12 response? (comparison of 30 mg, 60mg and 120 mg where drug 
is administered on an identical schedule); (2) does duration and schedule of loading affect 
Week 12 response? (comparison of 120mg administered as q2w x 7 and q2w x 3 followed by 
q4w x 2); (3) does frequency of administration affect longer term results? (comparison of Week 
24 response for the different 120mg dose regimens). 
The highest dose planned in this phase 2b study, 120mg, has shown adequate safety when 
administered q2w for three doses in the phase 1 study and appears to be toward the top of the 
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5.0 
STUDY POPULATION 
Prospective approvals of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, are not permitted. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all the following criteria apply: 
1. Ambulatory male and female subjects between 18 and 75 years of age at time of 
consent. 
2. Subject has had stable moderate to severe plaque-type psoriasis for at least 6 months 
prior to randomization (e.g., no morphology changes or significant flares of disease 
activity in the opinion of the investigator). 
3. Subject must be considered, in the opinion of the investigator, not adequately controlled 
by photo, topical or previous systemic treatments and a candidate for systemic biologic 
therapy. 
4. Subject has Investigator’s Global Assessment (IGA) ≥3, involved body surface area 
(BSA) ≥10% and PASI ≥12 at screening and at baseline. 
5. Subject is in the opinion of the investigator able to comply with the study procedures.  
6. Following verbal and written information about the study, subject must provide signed 
and dated informed consent before any study related activity is carried out. 
5.2 
Exclusion Criteria  
Subjects are excluded from the study if any of the following criteria apply: 
1. Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, or 
other skin conditions at the time of the screening visit (e.g., eczema) that would 
interfere with evaluations of psoriasis (Note: psoriatic arthritis is NOT exclusionary.) 
2. Subject has drug-induced psoriasis (i.e. new onset or current exacerbation from beta-
blockers, calcium channel inhibitors or lithium) 
3. Other medical conditions: 
a. At the time of consent, subject has a planned in-patient surgical intervention 
between baseline and the Week 52 evaluation. 
b. Subject has an active infection or history of infections as follows: 
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i. Any active infection for which systemic anti-infectives were used 
within 28 days prior to randomization. 
ii. A serious infection, defined as requiring hospitalization or intravenous 
anti-infectives within 8 weeks prior to randomization. 
iii. Any history of bone infection requiring surgical intervention and/or 
intravenous antibiotics. 
iv. Recurrent or chronic infections or other active infection that, in the 
opinion of the investigator, might cause this study to be detrimental to 
the subject. 
c. Subject has active tuberculosis. 
d. Subject has a positive QuantiFERON®-TB Gold test for tuberculosis at 
screening, or if the first test and a repeat test are both indeterminate, unless (i) 
subject has a known history of latent TB and has completed a course of 
treatment or (ii) subject has received sufficient treatment for latent TB to allow 
concomitant treatment with a biological therapy as per local guidelines (note 
these subjects must continue their concomitant latent TB treatment to 
completion while participating in the study). If these subjects are outside of the 
screening window (>28 days since consent) when they become eligible to 
participate, they should be fully re-screened for the study. 
e. Subject has an underlying condition (including, but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, 
infectious or gastrointestinal) which in the opinion of the investigator places the 
subject at unacceptable risk for receiving an immunomodulatory therapy. 
f. Subject has known history of inflammatory bowel disease. 
g. Subject with known chronic liver disease or tests positive for hepatitis B virus 
(HBV) infection or has antibodies to hepatitis C virus (HCV) at screening. See 
Section 10.5 Appendix 5. 
h. Subject has antibodies to human immunodeficiency virus (HIV) at screening.  
See Section 10.5, Appendix 5. 
i. Subject has history of heart failure, myocardial infarction or unstable angina 
pectoris within the past 12 months prior to randomization. 
j. Subject has uncontrolled hypertension characterized by two blood pressure 
measurements separated by at least 15 minutes with systolic >160mmHg or 
diastolic >100mmHg. 
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k. Subject has clinically significant electrocardiogram (ECG) abnormalities on 
centrally read ECG. 
l. Subject has any active malignancy, including evidence of cutaneous basal or 
squamous cell carcinoma or melanoma. 
m. Subject has history of malignancy within 5 years EXCEPT cutaneous squamous 
or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma 
which has been treated and considered cured. 
n. Subject has any concurrent medical condition that, in the opinion of the 
investigator, could cause this study to be detrimental to the subject. 
4. Subject has laboratory abnormalities at screening, including any of the following: 
a. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 x the 
upper limit of normal (one retest is allowed for aminotransferase 
abnormalities.) 
b. Serum direct bilirubin >1.5 mg/dL. 
c. White blood cell (WBC) count <3.00 x 103/µL. 
d. Absolute neutrophil count <1.50 x 103/µL. 
e. Absolute lymphocyte count <0.50 x 103/µL. 
f. Platelet count <100,000/µL. 
g. Creatinine clearance of <30mL/min (calculated via Cockcroft Gault). A 
subsequent 24-hour urine collection may be performed with the prior approval 
of the Medical Monitor, and if via urine collection the creatinine clearance is 
>30mL/min the subject is eligible for the study.    
AMENDMENT FOR CZECH REPUBLIC               
Creatinine clearance of <60 mL/min (calculated via Cockcroft Gault). A 
subsequent 24-hour urine collection may be performed with the prior approval 
of the Medical Monitor, and if via urine collection the creatinine clearance is 
>60mL/min the subject is eligible for the study.   
h. Any other laboratory abnormality, which, in the opinion of the investigator, will 
prevent the subject from completing the study or will interfere with the 
interpretation of the study results. 
5. Subject has used topical therapy as follows:  
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a. Topical psoriasis treatment within 14 days of randomization, including, but not 
limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, topical calcineurin inhibitors, retinoids, tazarotene, as well as 
emollients and other non-prescription topical products that contain urea, >3% 
salicylic acid, or alpha- or beta-hydroxyl acids, and medicated shampoos (e.g. 
those that contain >3% salicylic acid, corticosteroids, coal tar, or vitamin D3 
analogues). 
Exceptions: mild/least potent topical steroids are permitted during screening 
for use limited to the face, axillae, and/or genitalia but must be discontinued 
24 hours prior to the baseline visit (randomization). 
b. Bland emollients (without alpha or beta hydroxy acids) within 24 hours of 
baseline visit randomization. Note that as per Section 6.5 bland emollients 
(without alpha or beta hydroxy acids) may be used during the study but 
MAY NOT be used within 24 hours prior to any study visit. 
6. Subject has used the following within 28 days of randomization: ultraviolet A (UVA) 
light therapy (with or without psoralen); ultraviolet B (UVB) light therapy; excimer 
laser; oral retinoids; methotrexate; cyclosporine; systemically administered calcineurin 
inhibitors; azathioprine; thioguanine; hydroxyurea; cyclophosphamide; fumarates; 
apremilast; or oral or parenteral corticosteroids including intramuscular or 
intraarticular administration (exception: otic, nasal, ophthalmic, or inhaled 
corticosteroids within recommended doses is permitted); other non-biologic systemic 
therapy for psoriasis. 
7. Subject is not willing to limit ultraviolet (UV) light exposure (e.g. sunbathing and/or 
the use of tanning devices) during the study. 
8. Subject has received live vaccine(s) within 6 weeks of randomization. 
9. Subject has received prior treatment at any time before screening with any compound 
(marketed or investigational) targeting IL-17 (i.e. direct inhibitor, receptor blocker, 
etc.). 
10. Subject has received prior treatment at any time before screening with more than 2 
biologic therapies (ustekinumab, tumour necrosis factor (TNF) targeting therapies, or 
investigational therapies).  
11. Subject has received TNF targeting therapies in the 12 weeks prior to randomization, 
ustekinumab in the 6 months prior to randomization, or investigational biological 
therapies within 12 weeks, or within 5 half lives of randomization, whichever is the 
longer. 
12. Subject has known sensitivity to any of the products or components to be administered 
during dosing  
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13. Subject has a history or evidence of suicidal ideation or behavior within the 12 months 
prior to randomization or evidence of severe depression at screening or baseline [i.e. 
severity level 3, 4 or 5 based on an assessment with the electronic Columbia Suicide 
Severity Rating Scale (eC-SSRS)]. 
14. Subject has a history of chronic alcohol abuse or chronic drug abuse, or has used 
intravenous (IV) drugs in the past 2 years. 
15. Women of child bearing potential who are not willing to use highly effective methods 
of birth control during treatment and for 12 weeks after the last dose of study drug. See 
Section 10.4, Appendix 4 for definition of child bearing potential and guidance on 
highly effective methods of birth control. 
16. Subject has a positive serum pregnancy test during screening or a positive urine 
pregnancy test at baseline (Week 0, randomization visit) except those surgically sterile 
or at least 1 year postmenopausal.  
17. Subject is pregnant or breast feeding, or planning to become pregnant while enrolled 
in the study and for 12 weeks after the last dose of study drug. 
18. Male subjects who are not willing to use contraception during treatment and for 12 
weeks after the last dose of study drug. See Section 10.4, Appendix 4 for definition of 
permitted methods of contraception in male subjects.  
19. Subject will not be available for protocol required study visits or procedures, (e.g. 
venepuncture) to the best of the subject's and investigator's knowledge. 
20. Subject has any kind of disorder that, in the opinion of the investigator, may 
compromise the ability of the subject to give informed consent and/or to comply with 
all required study procedures. 
21. Subject is either 
a. currently enrolled in another interventional, investigational device or drug 
study. 
b. has been in another investigational device or drug study(s) in the 30 days prior 
to consent. 
22. Subject is an employee of the study sponsor (Bond Avillion 2 Development LP), 
Avillion LLP, EMD Serono, Merck KGaA or any contract research organization (CRO) 
associated with the study.  
23. Subject or subject’s immediate family is working for or employed by the investigator. 
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5.3 
Lifestyle Considerations 
5.3.1 
Meals and Dietary Restrictions 
Subjects should be fasting when they attend for the baseline (randomization) visit, and for 
Weeks 12, 24, 36 and 48. These visits should be conducted in the morning and the subject 
should not have had breakfast.  
5.3.2 
Caffeine, Alcohol, Tobacco, and Cannabis/Marijuana 
There no specific restrictions on caffeine, alcohol, tobacco, or cannabis/marijuana, all of which 
can be used in moderation during the study. Non-smokers should not start smoking during the 
study.  
5.3.3 
Activity 
UV light exposure (e.g. sunbathing and/or the use of tanning devices) must be limited for the 
course of the study.  
5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the study but are not 
randomized. A minimal set of screen failure information is required to ensure transparent 
reporting of screen failure subjects to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements9 and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) will not 
be rescreened. One central laboratory re-test for ALT and AST is permitted within the 28-day 
screening period. If treatment of latent tuberculosis is instigated and the use of biological 
therapy is permitted per local guidelines the subject may be enrolled into the study. In such 
cases, if the study screening period has extended beyond 28 days since consent, the subject 
should be fully re-consented and re-screened to check they remain eligible for the study. 
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6.0 
STUDY DRUGS 
Study drug is defined as any investigational product, marketed product or placebo, intended to 
be administered to a study subject according to the study protocol. All study drugs in this study 
are considered Investigational Medicinal Products (IMP). 
Study drugs must NOT be used for any purpose other than as described in this protocol, and 
this includes other human studies, animal investigations and in vitro testing. 
Only subjects enrolled in the study may receive study drugs and only authorised site staff may 
prepare, supply or administer study drugs.  
6.1 
Study Drugs Administered 
Study drugs will be administered by subcutaneous injection. Before all injections, the 
appropriate personnel and requirements to treat severe allergic reactions should be available. 
A physician must be available at the time of each injection.  
Treatment Groups 
1. Placebo, in 2 x 1mL subcutaneous injections, given at Week 0, 1, 2, 3, 4, 6, 8 and 10. 
(These subjects will then receive study drug: M1095, 120mg, in 2 x 1mL subcutaneous 
injections, i.e. 1mL study drug, 1 mL placebo, given at Week 12, 14, 16, and q4w). 
2. M1095, 30 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study drug, 1mL placebo, 
given at Week 0, 2, 4, 8, 12 and q4w. (These subjects will also receive placebo, in 2 x 
1mL subcutaneous injections, at Week 1, 3, 6, 10 and 14). 
3. M1095, 60 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study drug, 1mL placebo, 
given at Week 0, 2, 4, 8, 12 and q4w. (These subjects will also receive placebo, in 2 x 
1mL subcutaneous injections, at Week 1, 3, 6, 10 and 14). 
4. M1095, 120 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study drug, 1mL 
placebo, given at Week 0, 2, 4, 8, 12 and q8w. (These subjects will also receive placebo, 
in 2 x 1mL subcutaneous injections, at Week 1, 3, 6, 10, 14, 16, 24, 32 and 40). 
5. M1095, 120 mg, in 2 x 1mL subcutaneous injections, i.e. 1mL study drug, 1mL 
placebo, given at Week 0, 2, 4, 6, 8, 10, 12 and q4w. (These subjects will also receive 
placebo, in 2 x 1mL subcutaneous injections, at Week 1, 3 and 14). 
6. Secukinumab, 300mg, in 2 x 1mL (150mg/mL) subcutaneous injections, given at Week 
0, 1, 2, 3, 4, 8, 12 and q4w. (These subjects will also receive placebo, in 2 x 1mL 
subcutaneous injections, at Week 6, 10 and 14). 
The 30mg and 60mg M1095 doses (in Arms 2 and 3) will be escalated at Week 12 in subjects 
who have not achieved an IGA score of 0 or 1, as described in Section 6.6.1.  
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M1095 doses (in Arms 1 to 5) may be replaced by placebo at Week 24 as described in Section 
6.6.2.  
6.2 
Preparation/Handling/Storage/Accountability 
Further guidance and information can be found in the Study Drug Manual provided for the 
study.  
The investigator is responsible for study drug accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records). Study drug storage and 
accountability will be reviewed by the unblinded monitor during routine monitoring visits. 
Study drug will be provided as subject kits each containing 2 vials (A and B) of M1095 of the 
appropriate strength (60mg or 120mg) to reconstitute the randomized dose and/or matching 
placebo, and subject kits containing commercial secukinumab 2 x 150mg pre-filled syringes.  
M1095 and placebo will be supplied as a lyophilized powder in glass vials. The 30mg dose 
will be reconstituted from a 60mg vial with 1mL placebo and 1mL sterile water for injection 
(WFI), the 60mg dose will be reconstituted from a 60mg vial with 1mL sterile WFI, and the 
120mg dose will be reconstituted from a 120mg vial with 1mL sterile WFI. Secukinumab will 
be supplied as commercial pre-filled syringes, over-labelled and packaged for the study.   
All study drug must be stored in a secure, environmentally controlled, and monitored (manual 
or automated) area in accordance with the labelled storage conditions (2 to 8oC, 36 to 46oF) 
with access limited to the investigator and authorized site staff.  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drug received and any discrepancies must be reported 
and resolved before the study drug is used. 
Investigators and site staff are reminded to check temperatures daily (i.e., manually or by using 
alarm systems to alert of any excursions) and ensure that temperature monitoring device(s) is 
(are) working correctly as required for proper storage of study drug. Any temperature 
excursions should be documented and reported to the sponsor, noting any actions taken. Once 
a deviation is identified, study drug must be quarantined and not used until the sponsor 
provides documentation of permission that the study drug can be used. 
All study drugs will be prepared for injection by an unblinded preparer in syringes with 1mL 
volume. The syringes for injection will be provided to the site approved study drug 
administrator, who is also unblinded (see Section 6.3 for further details). The unblinded 
preparer and the unblinded administrator may be the same person. 
Study drug will be administered via subcutaneous injection. All doses are comprised of two 
injections, each of 1mL, which should be administered at least 5 centimetres apart on any 
quadrant of the abdomen or the upper thigh. The body location for injections should not be 
repeated at consecutive study visits. Injections should not be given in areas where the skin is 
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tender, bruised, erythematous, or indurated. Areas of the skin affected by psoriasis should be 
avoided as injection sites.  
For subjects assigned to M1095 or placebo, the site approved unblinded administrator will be 
instructed to inject the subject with 1ml of solution from vial A and 1ml of solution from vial 
B. Subjects assigned to secukinumab will be dosed with 2 x 150mg/mL pre-filled syringes, as 
directed. Blinded study personnel should not be in attendance while study drug is being 
prepared or administered. Used syringes should be placed immediately out of sight in a sealed 
sharps container.  
Subjects should be observed for approximately 2 hours after the first dose of study drug and 1 
hour for subsequent doses. At Week 12 all subjects should be observed for approximately 2 
hours. If a subject experiences symptoms indicative of an acute hypersensitivity reaction after 
an injection, this should be discussed with the Medical Monitor before the next study 
visit/injection. 
Regulatory agencies require accounting for the disposition of all study drugs received by each 
clinical site. The investigator is responsible for maintaining information related to drug 
disposition which at minimum consists of the date received, date dispensed, quantity dispensed 
and the subject to whom the drug was dispensed. 
At the end of the study, the investigator should return unused study drug and packaging to the 
sponsor’s representative. Local destruction may be permitted with the sponsor’s approval.  
6.3 
Measures to Minimize Bias: Randomization and Blinding 
All subjects will be centrally assigned to randomized study drug using an Interactive Response 
Technology System (IRT). Before the study is initiated, the log in information and directions 
for the IRT (including the process for emergency unblinding) will be provided to each site, 
plus a back up telephone number and call-in directions.  
Study drug will be dispensed at the study visits as summarized in the SoA (Section 1.3).  
Any study drug that is prepared but not administered to a subject should not be re-dispensed. 
Unblinding will only occur during the study in the case of subject emergencies where it is 
necessary to determine the subject’s treatment assignment to ensure the best course of medical 
management is taken. The IRT will be programmed with blind-breaking instructions. In case 
of an emergency, the investigator has the sole responsibility for determining if the unblinding 
of a subject’s treatment assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. While not required, it is recommended that the 
investigator should contact the Medical Monitor prior to unblinding unless this could delay 
emergency treatment of the subject. If a subject’s treatment assignment is unblinded, the 
sponsor must be notified within 24 hours of breaking the blind. The date and reason that the 
blind was broken must be recorded in the source documentation and electronic case record 
form (eCRF), as applicable.  
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The outer packaging of study kits will appear identical, but as the M1095 and placebo doses 
require reconstitution, and secukinumab is provided as commercially available pre-filled 
syringes (PFS), it is not possible to blind the study completely. An unblinded study drug 
preparer will be responsible for the reconstitution and dispensation of study drug and will 
endeavor to ensure that there are no differences in the time taken to dispense each arm of the 
study.  
Once syringes for injection have been prepared, they will be provided to the study drug 
administrator, who will also be unblinded.  
The study drug preparer and the study drug administrator may be the same person.  
 
Other than the study drug preparer and administrator, the study team (including the IGA and 
PASI assessors) will be completely blinded throughout the study and will be kept physically 
separate from the preparation and administration of study medication.   
The subject blind will be maintained by the use of M1095 and matched placebo. The syringes 
used for all M1095 and placebo doses will be identical. All subjects will receive two injections 
of 1mL at each visit. There is also physical protection of the blind. Subjects will be asked to 
wear an eye-mask for all injections.  
An unblinded interim analysis of 12-week data will occur at the completion of the 12-week 
period, while the study is still ongoing. This will be managed by an independent DMC and 
statistical analysis group to preserve the blinding. This data will be shared with firewalled 
individuals who are not directly involved in the conduct of the study.  
All members of the sponsor’s study team will be blinded to subject treatment assignments until 
all subjects complete 24 weeks and the database is locked, with all queries through Week 24 
resolved. After Week 24 data has been cleaned and locked, the study statistician and designated 
sponsor team members will be unblinded to perform analysis of key study endpoints. All other 
members of the sponsor’s study team, site staff (except the unblinded preparer) and subjects 
will remain blinded until the end of study. 
An unblinded study monitor will be assigned by the CRO to visit site and check the 
documentation maintained by the unblinded study preparer and administrator and all drug 
accountability records. The unblinded study monitor will not reveal any study details that could 
unblind the study to the blinded study monitor. In the event of a Quality Assurance audit, the 
auditor(s) will also be allowed access to unblinded study drug records at the site(s) to verify 
that randomization/dispensing has been performed accurately. 
Laboratory personnel performing the bioanalytical PK sample analysis may receive an open 
randomization list to enable analysis of relevant samples. In addition, a PK analyst and 
modelling/simulation scientist may receive an open randomization list to enable preparation of 
modelling/simulation activities. These individuals will not interact with site or CRO personnel. 
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Site personnel will enter the IGA score into the IRT prior to the study drug kit being assigned 
at Week 12.  
6.6.2 
Week 24 
Any subjects on M1095 who did not undergo dose escalation at Week 12 and who achieve an 
IGA score of 0 at Week 24 will have study drug withheld and will receive placebo q4w.  
Subsequently, if IGA score is 1 or more, these subjects will re-commence M1095 at the dose 
they received prior to Week 24 on a q4w regimen at the visits scheduled by the protocol until 
the end of the treatment period. Dose will not be withheld for a second time, irrespective of 
subsequent IGA scores.  
At Week 24, subjects on secukinumab will continue to be treated q4w.  
Site personnel will enter the IGA score into the IRT prior to the study drug kit being assigned 
at Week 24, 28, 32, 36, 40 and 44. 
 
At Week 24, the investigator should carefully consider the subject’s response and if there has 
been a worsening of psoriasis compared to baseline then the investigator should consider 
discontinuing the subject from the study if they are not receiving adequate benefit from their 
participation. 
6.7 
Treatment after the End of the Study 
The final dose of study drug will be administered at the Week 44 visit with the final study visit 
occurring at Week 52.  
Subjects that discontinue study treatment during the study should complete Early 
Discontinuation, with visits approximately 4 weeks (28 days) and 8 weeks (56 days) after the 
last dose of study drug (see the SoA, Section 1.3, and Sections 7.2 and 8.1.11). Once the Early 
Discontinuation visits have been completed, subjects will be contacted by telephone as per the 
q4w study schedule.     
After study completion at Week 52, or after completion of the Early Discontinuation visits, 
subjects should be treated as per local guidance and physician recommendation.
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7.0 
DISCONTINUATION OF STUDY DRUG AND SUBJECT 
DISCONTINUATION/WITHDRAWAL  
Subjects should be discontinued from study drug if any of the criteria described in Section 7.1 
are met. Such subjects will continue to be followed for safety assessments as described in the 
SoA, Section 1.3, and Section 8.1.11.  
 
Subjects may voluntarily withdraw from the study for any reason at any time, or be withdrawn 
by the investigator or the sponsor as per Section 7.2. The investigator should strongly 
recommend that withdrawn subjects return for follow-up visits approximately 28 days and 56 
days after the last dose of study drug to assess their safety and, if willing, to assess duration of 
effect (e.g. rebound assessments). The information to be collected is identical to the Early 
Discontinuation visit, as described in the SoA (Section 1.3) and Section 8.1.11. 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Such subjects will be 
considered to have discontinued the study. 
Subjects who are prematurely discontinued from study treatment, or who have chosen to 
withdraw from the study, or who are lost to follow up, will not be replaced. 
7.1 
Discontinuation of Study Drug 
See the SoA (Section 1.3) and Section 8.1.11 for data to be collected at the time of study drug 
discontinuation, plus follow-up and for evaluations that need to be completed. 
Study treatment must be discontinued under the following circumstances (all cases should be 
discussed with the Medical Monitor): 
• Withdrawal of consent 
• Emergence of the following:  
o AE considered related to study treatment including: 
 Clinically significant systemic hypersensitivity reaction following 
administration of study drug that does not respond to symptomatic 
treatment. 
 Severe (grade 3 or higher Common Terminology Criteria for AEs 
(CTCAE) Version 5.0) anaphylaxis (symptomatic bronchospasm, with 
or without urticaria; parenteral intervention indicated; allergy-related 
edema / angioedema; hypotension).  
 Severe (grade 3 or higher CTCAE Version 5.0) serum sickness (severe 
arthralgia or arthritis; extensive rash, with steroids or intravenous fluids 
indicated). 
• Note that if a subject experiences symptoms consistent with a 
grade 2 serum sickness (moderate arthralgia, fever, rash, or 
urticaria, with antihistamine treatment indicated), and causality 
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by the study drug cannot be ruled out, the subject should return 
to site for an unscheduled visit. There should be a documented 
assessment and physical examination concurrent with the event. 
Grade 2 serum sickness does not require discontinuation of 
study drug, however the Medical Monitor should be informed. 
 Any other severe (grade 3 CTCAE Version 5.0) event that does not 
resolve with supportive care. 
 Any life threatening (grade 4 CTCAE Version 5.0) event. 
o Any other AE that in the judgment of the investigator, and considering the 
subject’s overall status, prevent the subject from continuing to participate in the 
study (for example, sepsis or serious infection). 
o Laboratory findings as follows regardless of CTCAE Version 5.0 grade:  
 Total WBC count <2.00 x 103/µL.  
 Total ANC <1.00 x 103/µL. 
 Platelet count <50,000/µL. 
 Elevated transaminases (ALT or AST) >3 x upper limit of normal 
(ULN) and associated with total bilirubin >2 x ULN (without 
accompanying alkaline phosphatase elevation >2 x ULN suggestive of 
cholestasis) – i.e. subject meets Hy’s Law criteria. 
 Elevated transaminases (ALT or AST) >5 x ULN without clear 
alternative etiology (tests should be repeated within 72 hours to verify 
the result prior to discontinuation.) 
 Any laboratory abnormalities that in the judgment of the investigator, 
taking into consideration the subject’s overall status, prevents the 
subject from continuing participation in the study. 
o Pregnancy (see Sections 8.5.5 and 10.4, Appendix 4).  
o The subject develops a malignancy. (Exception: Subjects may be allowed to 
continue if they develop no more than 2 non-melanoma skin cancers (NMSC) 
during the study) 
o Use of prohibited treatment as per recommendations in Section 6.5. 
• Any other protocol deviation that results in a significant risk to the subject’s safety. 
• Administrative decision by the investigator, the sponsor or it’s designee to stop the 
subject’s study treatment for medical, safety, regulatory, or other reasons consistent 
with applicable laws, regulations, and good clinical practice (GCP).  
• Subject noncompliance (significant violation of protocol requirements or missing two 
consecutive visits). 
 
In addition to these requirements for study treatment discontinuation, the investigator should 
discontinue study treatment for a given subject if, on balance, continuation would be 
detrimental to the subject’s well-being. The investigator should carefully consider the subject’s 
response at Week 24 and if there has been a worsening of psoriasis compared to baseline then 
the investigator should consider discontinuing the subject from the study if they are not 
receiving adequate benefit from their participation. 
 
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The appropriate personnel from the study site and the sponsor or it’s designee will assess 
whether study treatment should be discontinued for any subject whose treatment code has been 
broken inadvertently for any reason. 
 
Subjects who discontinue study treatment should NOT be considered withdrawn from the 
study. They will continue to be followed up for assessments. See the SoA, Section 1.3 and 
Section 8.1.11 for the required assessments of these subjects after study treatment 
discontinuation. 
 
Subjects should be considered to still be on study unless any of the criteria for study withdrawal 
are met (see Section 7.2). 
7.1.1 
Temporary Discontinuation  
Temporary discontinuations are not permitted in this study. Any missed doses should be 
discussed with the Medical Monitor.  
7.1.2 
Rechallenge 
Rechallenge is defined as the re-introduction of study drug following a temporary withdrawal/ 
dose hold for safety related reasons.  
Rechallenge is not permitted for any reason including after study drug being withheld due to 
related/possibly related AEs; in these circumstances the Medical Monitors should be consulted 
prior to withholding study drug and the subject considered for permanent discontinuation.  
7.2 
Subject Withdrawal from the Study 
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator or the sponsor for safety, behavioral, 
compliance, or administrative reasons. 
 
If the subject withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
 
If a subject withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the site study records. 
 
If premature withdrawal occurs for any reason, the investigator must make every effort to 
determine the primary reason for a subject’s premature withdrawal from the study and record 
this information on the applicable eCRF. The withdrawn subjects must return for a follow-up 
visit approximately 28 days after the last dose of study drug to assess their efficacy, safety, 
quality of life (QoL), report any AEs and assess duration of effect (e.g. rebound assessments). 
A further visit/telephone call should be conducted approximately 56 days after the last dose of 
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study drug to follow up on AEs. The information to be collected is identical to the Early 
Discontinuation visit 1 and visit 2, as described in the SoA (Section 1.3) and Section 8.1.11. 
7.3 
Lost to Follow Up 
A subject will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
 
For subjects who are lost to follow-up, the investigator should show "due diligence" by 
documenting in the source documents steps taken to contact the subject. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible. The subject should be counselled on the importance of maintaining the 
assigned visit schedule and it should be ascertained whether the subject wishes to 
and/or should continue in the study. 
• Before a subject is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, three telephone calls 
and, if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• Should the subject continue to be unreachable, he/she will be considered to have 
discontinued from the study. 
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8.0 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). Study visit 
dates are scheduled relative to Week 0.  
• Protocol waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue 
study drug. 
• Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all subjects screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
• Patient Reported Outcomes (PROs) during any visit should be conducted before other 
tests, procedures, or consultations.  
• IGA, BSA and PASI during any visit should be conducted after the PROs (if applicable) 
and before other tests, procedures and consultations. As far as possible, the same 
evaluator should perform the IGA, BSA and PASI at all visits for a particular subject, 
especially at Week 0 (randomization), Week 12, and Week 24. 
• The maximum amount of blood collected from each subject over the duration of the 
study, including any extra assessments that may be required, will not exceed 565mL, 
with a maximum 50mL taken at any visit. Repeat or unscheduled samples may be taken 
for safety reasons or for technical issues with the samples. 
8.1 
Study Procedures 
8.1.1 
Screening 
Subjects will attend for a Screening Visit during the 4 weeks (28 days) prior to Week 
0/randomization. This is designed to assess the inclusion/exclusion criteria and establish 
baseline characteristics.  
The approved consent form must be signed and dated by the subject and the consenting 
investigator prior to any study related procedures being conducted. AEs will be collected from 
the time that consent is signed. 
IGA, BSA and PASI should be performed before any other study procedures, assessments or 
consultations. The following assessments will be performed and information collected:- 
• Demographics 
• Inclusion/Exclusion Criteria 
• Psoriasis Medical History 
• Prior Psoriasis Treatments 
• Other Medical History 
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• IGA 
• BSA 
• PASI 
• Adverse events are to be recorded from the time of consent  
• Concomitant Medications 
• Skin Evaluation 
• Physical Examination 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Urinalysis (Local) 
• Serum Pregnancy Test (Central Laboratory) 
• ECG (Standard 12 Lead, Central ECG Laboratory) 
• QuantiFERON®-TB Gold Test (Local or Central Laboratory)  
o If a local or central Quantiferon TB test result is 
‘indeterminate’ the test must be repeated during the 
screening period.  
o If any Quantiferon TB test is ‘positive’ or if the first test 
and the repeat test are both ‘indeterminate’, the subject 
must be referred for tuberculosis workup per local 
guidelines.  
o If any Quantiferon TB test is ‘positive’ or if the first test 
and the repeat test are both ‘indeterminate’, the subject is 
eligible for randomization if (i) they have a known history 
of latent TB and have completed a course of treatment or 
(ii) they have has received sufficient treatment for latent 
TB to allow concomitant treatment with a biological 
therapy as per local guidelines (note these subjects must 
continue their concomitant latent TB treatment to 
completion while participating in the study, and if these 
subjects are outside of the screening window (>28 days 
since consent) when they become eligible to participate, 
they should be fully re-screened for the study). 
o If any Quantiferon TB test is ‘positive’ or if the first test 
and the repeat test are both ‘indeterminate’, the subject is 
not eligible for randomization if either ‘active tuberculosis 
is present’ or if ‘latent tuberculosis is present and is 
untreated per local guidelines.’  
• HBV, HCV and HIV Testing (Central Laboratory), Section 10.5,   
Appendix 5 
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• Chest X-Ray (CXR) – CXR within 3 months of consent is considered 
acceptable. When performed as part of the Screening visit, the chest X-
ray should be the last study procedure to be completed, as this will 
prevent unnecessary exposure to radiation if the subject is found to be 
ineligible following an earlier procedure. Investigator should follow up 
the results of the chest X-ray with the Medical Monitor if clinically 
indicated.   
8.1.2 
Week 0 / Randomization 
At Week 0, subjects who meet the inclusion/exclusion criteria will be randomized.  
Fasting blood samples should be obtained, so the visit should be conducted in the morning and 
the subject should not have had breakfast.  
Patient reported outcomes (PRO) i.e. DLQI, EQ-PSO, SF-36, PHQ-8, and eC-SSRS should be 
performed before any other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations. 
The first dose of study drug should be administered after completion of all other study 
procedures.  
The following assessments will be performed and information collected:- 
• Repeat check of Inclusion/Exclusion Criteria 
• AEs 
• Concomitant Medications 
• DLQI 
• EQ-PSO 
• SF-36 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• Skin Evaluation 
• Physical Examination 
• Vital Signs 
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• Laboratory Analysis Chemistry and Haematology (Fasting, Central 
Laboratory) 
• Urinalysis (Local) 
• Urine Pregnancy Test (Local) – if positive, study drug must be withheld 
and a Serum Pregnancy Test (Central Laboratory) performed 
• Blood Sample for Immunogenicity (must be pre-dose) 
• Blood Sample for Pharmacokinetics (must be pre-dose) 
• Randomization (via IRT) 
• Study Treatment (allocated via IRT) 
8.1.3 
Weeks 1, 3, 6, 10 
There is a visit window of ±1 day for Weeks 1 and 3, and ±2 days for Weeks 6 and 10.  
IGA, BSA and PASI should be performed before any other study procedures, assessments or 
consultations.  
Study drug should be administered after completion of all other study procedures.  
The following assessments will be performed and information collected:- 
 
• IGA 
• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Vital Signs 
• Study Treatment (allocated via IRT) 
8.1.4 
Week 2 
There is a visit window of ±1 day for the Week 2 visit.  
IGA, BSA and PASI should be performed before any other study procedures, assessments or 
consultations.  
Study drug should be administered after completion of all other study procedures. 
The following assessments will be performed and information collected: 
• IGA 
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• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Blood Sample for Immunogenicity (must be pre-dose)  
• Blood Sample for Pharmacokinetics (must be pre-dose) 
• Study Treatment (allocated via IRT)  
8.1.5 
Week 4 
There is a visit window of ±1 day for the Week 4 visit. 
Patient reported outcomes (PRO) i.e. PHQ-8, and eC-SSRS should be performed before any 
other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations. 
Study drug should be administered after completion of all other study procedures. 
The following assessments will be performed and information collected: 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Physical Examination 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Urine Pregnancy Test (Local) – if positive, study drug must be withheld 
and a Serum Pregnancy Test (Central Laboratory) performed 
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• Blood Sample for Immunogenicity (must be pre-dose)  
• Blood Sample for Pharmacokinetics (must be pre-dose) 
• Study Treatment (allocated via IRT)  
8.1.6 
Weeks 8, 44, 52 
There is a visit window of ±2 days for Week 8, and ±5 days for Weeks 44 and 52.  
Patient reported outcomes (PRO) i.e. PHQ-8, and eC-SSRS should be performed before any 
other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations. 
Study drug should be administered after completion of all other study procedures. 
The following assessments will be performed and information collected: 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• AEs - SAEs and AEs will be followed until resolution, stabilization or 
the event is otherwise explained or the subject is lost to follow up (see 
Section 7.3). AEs not considered serious or as an AESI will be 
considered ongoing if they have not resolved by Week 52. 
• Concomitant Medications 
• Skin Evaluation 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Urine Pregnancy Test (Local) – if positive, study drug must be withheld 
and a Serum Pregnancy Test (Central Laboratory) performed 
• Blood Sample for Immunogenicity (must be pre-dose) – subjects 
testing positive at Week 52 may be requested to provide another sample 
6 to 12 months after study completion  
• Blood Sample for Pharmacokinetics (must be pre-dose) 
• Study Treatment (allocated via IRT) with the exception of Week 52 
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• At Week 52, male and female subjects of child bearing potential should 
be reminded that they must use highly effective contraception for a 
further 4 weeks  
8.1.7 
Weeks 12, 24, 36, 48  
There is a visit window of ±2 days for Weeks 12 and 24, and ±5 days for Weeks 36 and 48. 
Fasting blood samples should be obtained, so the visit should be conducted in the morning and 
the subject should not have had breakfast.  
Patient reported outcomes (PRO) i.e. DLQI, EQ-PSO, SF-36, PHQ-8, and eC-SSRS should be 
performed before any other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations.  
Study drug should be administered after completion of all other study procedures.   
The following assessments will be performed and information collected:- 
• DLQI 
• EQ-PSO 
• SF-36 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Physical Examination 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Fasting, Central 
Laboratory) 
• Urinalysis (Local) 
• Urine Pregnancy Test (Local) – if positive, study drug must be withheld 
and a Serum Pregnancy Test (Central Laboratory) performed 
• ECG (Standard 12 Lead, Central ECG Laboratory) 
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• Blood Sample for Immunogenicity (must be pre-dose) 
• Blood Sample for Pharmacokinetics (must be pre-dose) 
• Study Treatment (allocated via IRT) with the exception of Week 48 
• At Week 24, the investigator should carefully consider the subject’s 
response and if there has been a worsening of psoriasis compared to 
baseline then the investigator should consider discontinuing the subject 
from the study if they are not receiving adequate benefit from their 
participation. 
 
8.1.8 
Week 14 
There is a visit window of ±2 days for the Week 14 visit. 
IGA, BSA and PASI should be performed before any other study procedures, assessments or 
consultations.  
Study drug should be administered after completion of all other study procedures. 
The following assessments will be performed and information collected:- 
• IGA 
• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Study Treatment (allocated via IRT) 
8.1.9 
Week 16, 20, 28, 32, 40 
There is a visit window of ±2 days for Weeks 16 and 20, and ±5 days for Weeks 28, 32 and 
40.  
Patient reported outcomes (PRO) i.e. PHQ-8, and eC-SSRS should be performed before any 
other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations. 
Study drug should be administered after completion of all other study procedures. 
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The following assessments will be performed and information collected: 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• AEs 
• Concomitant Medications 
• Skin Evaluation 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Urine Pregnancy Test (Local) – if positive, study drug must be withheld 
and a Serum Pregnancy Test (Central Laboratory) performed 
• Study Treatment (allocated via IRT) 
8.1.10 
Unscheduled Visit  
Subjects may return to site for an Unscheduled Visit as clinically indicated. Laboratory 
assessments performed at an Unscheduled Visit should be sent to the central laboratory.  
All assessments should be documented in the medical record and entered in the eCRF.  
8.1.11 
Early Discontinuation 
The Early Discontinuation Visit involves two contacts with the subjects. The subject should 
attend the study site as close to possible to 4 weeks (28 days) after the last dose of study drug, 
and prior to the initiation of any other biological therapy. The reason for discontinuation should 
be discussed with the Medical Monitor. All subjects should then have further follow up either 
by telephone, or if they have ongoing SAEs or AEs, by attending the study site approximately 
8 weeks (56 days) after the last dose of study drug to report any new, and follow up any existing 
AEs.  
Patient reported outcomes (PRO) i.e. DLQI, EQ-PSO, SF-36, PHQ-8, and eC-SSRS should be 
performed before any other study procedures, assessments or consultations.  
IGA, BSA and PASI should be conducted after the PROs and before other tests, procedures 
and consultations. 
 
The following assessments will be performed and information collected:- 
 
 
Visit 1 – As close as possible to 4 weeks (28 days) after the last dose of study drug, and  
       
prior to the initiation of any other biological therapy. 
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• DLQI 
• EQ-PSO 
• SF-36 
• PHQ-8 
• eC-SSRS 
• IGA 
• BSA 
• PASI 
• AEs  
• Concomitant Medications 
• Skin Evaluation 
• Physical Examination 
• Vital Signs 
• Laboratory Analysis Chemistry and Haematology (Central Laboratory) 
• Urinalysis (Local) 
• Urine Pregnancy Test (Local) 
• ECG (Standard 12 Lead, Central ECG Laboratory) 
• Blood Sample for Immunogenicity – subjects testing positive may be 
requested to provide another sample six to twelve months after study 
completion  
• Blood Sample for Pharmacokinetics 
Visit 2 / Telephone Call – As close as possible to 8 weeks (56 days) after the last dose 
of study drug  
• AEs  
• Concomitant medication  
• Male and female subjects of child bearing potential should be reminded 
that they must use highly effective contraception for a further 4 weeks  
Following completion of the Early Discontinuation visits, subjects will continue to be 
contacted by telephone q4w as per the study schedule up to Week 52. The following 
information will be collected. 
• AEs 
• Concomitant medication 
• Any new treatments for psoriasis 
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8.2 
Efficacy Assessments 
Efficacy evaluations selected for this study are consistent with those used to evaluate other 
therapies for psoriasis.  
The IGA and PASI will be administered by site personnel according to the SoA (Section 1.3). 
All assessors of IGA and PASI must be qualified, experienced in evaluating subjects with 
psoriasis in clinical trials, and have completed study specific training in IGA and PASI rating. 
It is recommended that the same assessor conducts the IGA and PASI at all visits for a 
particular subject, but especially at Week 0 (randomization), Week 12, and Week 24.  
8.2.1 
Investigator’s Global Assessment (IGA mod 2011) 
IGA will be conducted for overall psoriatic disease as indicated in the SoA (Section 1.3).  
The IGA rating scale for overall psoriatic disease is shown in Section 10.6.1, Appendix 6.  
The explanations/descriptions of the points on the scale have been improved to ensure 
appropriate differentiation between the points.10 The IGA mod 2011 is thought to better 
correlate with PASI 90 responses. 
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the subject’s 
previous disease states, whether at baseline or at a previous visit. 
The IGA mod 2011 score will initially be recorded on paper, and then entered in the IRT/eCRF. 
8.2.2 
Assessment of Total Body Surface Area (BSA) and Psoriasis Area and Severity 
Index (PASI) 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of 
areas affected, including head, trunk, upper limbs and lower limbs (see Section 10.6.2, 
Appendix 6).  
The PASI combines assessments of the extent of body-surface area involvement in 4 
anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, 
and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for 
no psoriasis to 72.0 for the most severe disease.11, 12 See Section 10.6.2, Appendix 6 for details. 
Subjects achieving PASI 75, PASI 90, or PASI 100 are defined as having an improvement of 
at least 75%, 90%, or 100%, respectively, in PASI score from baseline.  
The site will initially record assessments on paper, and will then enter the data into the eCRF, 
which will auto-calculate the PASI score (no manual PASI calculations will be performed by 
the site). 
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The instrument essentially consists of 2 pages – the EQ-5D descriptive system and the EQ 
visual analogue scale (VAS). The EQ-5D descriptive system comprises the following 5 
dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each 
dimension has 3 response levels: no problems, some problems, severe problems. The subject 
is asked to indicate their health state by ticking in the box against the most appropriate 
statement in each of the 5 dimensions. In the EQ-PSO two additional dimensions, skin irritation 
and self confidence, have been added to make the questionnaire more disease specific for 
psoriasis.17 
The VAS records the subject’s self-rated health on a vertical, VAS where the endpoints are 
labelled ‘Best imaginable health state’ and ‘Worst imaginable helath state.’ This information 
can be used as a quantitative measure of health outcome as judged by the individual 
respondents. 
The EQ-PSO questionnaire will be completed by the subject as indicated in the SoA (Section 
1.3). It will be completed using an electronic tablet device.  
8.4 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA (Section 1.3).  
Safety assessments will include collection of AEs, skin evaluation, laboratory values, vital 
signs, ECGs, drug discontinuations, and instruments to assess depression and suicidality 
[electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) and Personal Health 
Questionnaire Depression Scale (PHQ-8)]. Blinded data will be reviewed during the study. An 
independent Data Monitoring Committee (DMC) will have access to unblinded information 
and will conduct periodic scheduled reviews as well as ad hoc reviews as needed. 
8.4.1 
Physical Examination 
A complete physical examination will include, at a minimum, assessments of the skin, 
cardiovascular, respiratory, gastrointestinal and neurological systems. Weight will also be 
measured and recorded. 
Height will be measured at screening only.  
8.4.2 
Skin Evaluation 
Subjects are expected to manifest skin findings associated with psoriasis which may include 
stable disease, worsening disease, or improving disease.  
If a subject develops a clinically significant cutaneous rash that is not typical of a psoriatic 
picture, then the following evaluations should be conducted: 
• 
Photographs  
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o Upper and lower body, front and back, 4 pictures in total. Further close up 
pictures (15cm x 15cm, 6 inches x 6 inches) should be taken of any areas of 
interest.  
• 
Skin biopsy  
o Two ≥4mm punch biopsies, one of normal skin, one within the rash. 
• 
Skin culture 
Detailed instructions for these evaluations will be provided as Skin Evaluation Instructions 
for the study. 
The Medical Monitor should be notified if photographs/skin biopsy/skin culture are being 
conducted and the subject should be treated as indicated while he/she continues study 
therapy. 
8.4.3 
Vital Signs 
Vital signs will be measured after at least 5 minutes rest, and will include temperature (oral, 
axillary, core, temporal, or tympanic), sitting or supine blood pressure and heart rate. 
8.4.4 
Electrocardiograms 
12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an ECG machine 
that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.  
At each time point, triplicate ECGs are required. Three individual ECG tracings should be 
obtained as closely as possible in succession, but no more than 2 minutes apart. The full set of 
triplicates should be completed in less than 4 minutes. 
ECG should also be performed at any time in the study if clinically indicated. 
Digital ECGs will be transmitted to a central vendor who will assess ECG measurements for 
screening requirements prior to randomization.  
The investigator is to assess ECG measurements for safety and should report any clinically 
significant findings as adverse events.  
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8.4.5 
Clinical Safety Laboratory Assessments 
See Section 10.2, Appendix 2 for the list of clinical laboratory tests to be performed by the 
central laboratory and the SoA (Section 1.3) for the timing and frequency.  
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. 
Laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless 
judged by the investigator to be more severe than expected for the subject's condition. 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study or within eight weeks after the last dose of study drug should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the investigator or Medical Monitor. 
o All protocol-required laboratory assessments, as defined in Section 10.2, 
Appendix 2, must be conducted in accordance with the laboratory manual and 
the SoA (Section 1.3).  
o If laboratory values from non-protocol specified laboratory assessments 
performed at the study site’s local laboratory require a change in subject 
management or are considered clinically significant by the investigator (e.g., 
SAE or AE or dose modification), then the values must be recorded in the 
eCRF.  
8.4.6 
Depression and Suicidal Risk Monitoring  
In studies of brodalumab, there have been reports of suicidal ideation or behavior. The sponsor 
considers it important to monitor for such events before and during this clinical study. 
Subjects being treated in this study should be monitored appropriately and observed closely 
for suicidal ideation and behavior or any other unusual changes in behavior. Consideration 
should be given to discontinuing study drug in subjects who experience signs of suicidal 
ideation or behavior.  
Families and caregivers of study subjects should be instructed to monitor for the emergence of 
unusual changes in behavior, as well as the emergence of suicidal ideation and behavior, and 
to report such symptoms immediately to the study investigator. 
Baseline assessment of suicidal ideation and behavior and treatment-emergent suicidal ideation 
and behavior will be assessed during the study using the electronic Columbia Suicide Severity 
Rating Scale (e-C-SSRS). Depression will be assessed using the Patient Health Questionnaire-
8 (PHQ-8).  
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8.4.6.1 
Electronic Self Rated Version, Columbia-Suicide Severity Rating Scale     
(eC-SSRS) 
The eC-SSRS is a standardized and validated instrument developed for the assessment of the 
severity and frequency of suicidal ideation and behavior.18, 19, 20 Subjects respond to 
standardized clinical questions that are presented in a uniform fashion. The eC-SSRS defines 
five subtypes of suicidal ideation and behavior in addition to self-injurious behavior with no 
suicidal intent. The eC-SSRS takes approximately 3 to 10 minutes to complete. 
The eC-SSRS questionnaire will be completed by the subject as indicated in the SoA (Section 
1.3). It will be completed using an electronic tablet device.  
 
8.4.6.2 
Patient Health Questionnaire (PHQ-8) 
The PHQ-8 is a validated and widely used eight-item version of the Patient Health 
Questionnaire depression scale designed to clinically assess subjects for symptoms and signs 
of depression.21, 22 The PHQ-8 takes approximately 3 minutes to complete and will be 
completed by the subject as indicated in the SoA (Section 1.3). It will be completed using an 
electronic tablet device. 
8.5 
Adverse Events (AEs) and Serious Adverse Events (SAEs) 
The definitions of an AE or SAE can be found in Section 10.3, Appendix 3. 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally authorized representative).  
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or 
that caused the subject to discontinue the study drug. 
Adverse events of special interest (AESI) include cytopenias, liver function test 
changes/enzyme elevations, infections, injection-site reactions, allergic/hypersensitivity 
reactions, cerebrocardiovascular events, malignancies, depression, Crohn’s disease and 
ulcerative colitis.  These events are based on Phase 1 data and findings with other IL-17 
modulating drugs.  Additional adverse events may be identified as being of special interest 
during the study and prior to the first unblinding.  Formal pre-specified evaluations beyond the 
discontinuation criteria in Section 7.1 are not planned at this time. 
If a subject reports symptoms consistent with a grade 2 serum sickness while between study 
visits, and causality by the study drug cannot be ruled out, the subject should return to site for 
an unscheduled visit if symptoms recur after the next dose. There should be a documented 
assessment and physical examination concurrent with the event 
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8.5.1 
Time Period and Frequency for Collecting AE and SAE Information  
AEs will be collected from the signing of the informed consent form (ICF).  
Medical conditions that begin before the start of study drug but after obtaining informed 
consent will be recorded on the Medical History/Current Medical Conditions section of the 
eCRF, not the AE section, unless related to study procedures. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours, as indicated 
in Section 10.3, Appendix 3. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
Investigators are not obligated to actively seek AE or SAE information after the conclusion of 
a subject’s study participation. However, if the investigator learns of any SAE, including a 
death, at any time after a subject has been discharged from the study, and he/she considers the 
event to be reasonably related to the study drug or study participation, the investigator must 
promptly notify the sponsor. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3, 
Appendix 3. 
8.5.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences.  
8.5.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. SAEs and AEs will be followed until resolution, stabilization, 
the event is otherwise explained, or the subject is lost to follow-up (as defined in Section 7.3). 
AEs not considered serious or as an AESI will be considered ongoing if they have not resolved 
by Week 52. Further information on follow-up procedures is given in Section 10.3, Appendix 
3. 
8.5.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a study 
drug under clinical investigation are met.  
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
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regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. AEs/SAEs must be followed up and reported as appropriate for at 
least 8 weeks (5 terminal half lives) after the last study dose. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then 
file it along with the Investigator’s Brochure and will notify the IRB/IEC if appropriate 
according to local requirements.  
8.5.5 
Pregnancy 
Details of all pregnancies in female subjects and female partners of male subjects will be 
collected after the start of study treatment and until at least 12 weeks (>5 terminal half lives) 
after the last study dose.  
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Section 10.4, Appendix 
4. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and should be reported to the sponsor or 
designee within 24 hours. 
8.5.6 
Cardiovascular and Death Events 
Cardiovascular AEs should be reported as AEs/SAEs as described in Sections 8.5 and 10.3, 
Appendix 3.  
Any subject deaths that occur during the study should be considered SAEs and reported as per 
Sections 8.5 and 10.3, Appendix 3. If a death occurs, the investigator may be asked to provide 
a copy of any post-mortem findings including histopathology. 
8.5.7 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs 
All AEs and outcomes should be reported as described in Sections 8.5 and 10.3, Appendix 3.  
8.6 
Overdose and Medication Errors 
There is no data regarding overdose of M1095.  
Secukinumab doses of up to 30 mg/kg intravenously have been administered in clinical trials 
without dose-limiting toxicity. In the event of overdosage, it is recommended that the subject 
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be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic 
treatment be instituted immediately. 
Medication errors may result, in this study, from the administration of an unassigned treatment 
to the wrong subject, errors related to storage requirements, or administration of an expired 
product. All overdoses occurring to a study subject are to be captured on the AE page of the 
eCRFs and on the SAE form when appropriate. In the event of medication dosing error, the 
sponsor should be notified immediately. 
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including: 
• 
Medication errors involving subject exposure to the study drug.  
• 
Potential medication errors or uses outside of what is foreseen in the protocol that do or do 
not involve the participating subject. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error, and, if applicable, any associated AE(s) is captured on an 
AE eCRF page.  
8.7 
Pharmacokinetics 
Pharmacokinetic samples will be collected at the timepoints specified on the SoA (Section 
1.3). 
Samples will be shipped initially to the study’s central laboratory and tested by the sponsor or 
sponsor's designee. 
Serum M1095 levels will be assessed at trough (i.e. before study drug is given) at the following 
visits: Weeks 0, 2, 4, 8, 12, 24, 36, 44, 48, 52 and Early Discontinuation. M1095 serum 
concentrations will be summarized at these timepoints.  
Drug concentration information will not be reported to investigative sites or blinded personnel 
until the study has been unblinded. 
Details of the analysis will be provided either in the Statistical Analysis Plan (SAP), or in a 
separate PK Plan, prior to the analysis taking place. 
8.8 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.9 
Genetics 
Planned genetic analysis is not performed in this study. Unscheduled genomic biomarkers may 
be assessed as described in Section 8.10. 
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8.10 
Biomarkers 
Biomarkers are not routinely evaluated in this study. However, if a subject develops a clinically 
significant cutaneous rash that is not typical of psoriasis, two ≥4mm punch biopsies, one of 
normal skin, and one from skin within the rash will be obtained. The biopsies will be prepared 
and sent to a specialist laboratory for analysis of genomic biomarkers, specifically the 
expression of inflammatory mediators that characterize various immune reactions.  
8.10.1 
Immunogenicity Assessments 
Antibodies to M1095 will be evaluated in serum samples collected at the timepoints specified 
on the SoA (Section 1.3)  
Samples will be shipped initially to the study’s central laboratory and tested by the sponsor or 
sponsor's designee. 
Serum anti-drug antibodies will be assessed at trough (i.e. before study drug is given) at the 
following visits: Weeks 0, 2, 4, 8, 12, 24, 36, 44, 48, 52 and Early Discontinuation.   
Serum samples will be screened for antibodies binding to M1095 and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 
antibodies to M1095 and/or further characterize the immunogenicity of M1095. 
The detection and characterization of antibodies to M1095 will be performed using a validated 
assay method by or under the supervision of the sponsor. All samples collected for detection 
of antibodies to study drug will also be evaluated for M1095 serum concentration (see Section 
8.7) to enable interpretation of the antibody data. Positive samples for anti-drug antibodies will 
be evaluated to determine if the antibodies are neutralizing or non-neutralizing.   
If a subject’s final anti-drug antibody sample is positive (i.e. sample from Week 52 or sample 
from an Early Discontinuation visit) then the sponsor may request an addition sample be 
collected approximately six to twelve months after completion of the study. Subjects will be 
informed of this in the consent form and will have the option to refuse this additional sample.   
With a subject’s consent, samples may be stored following the last subject’s last visit for the 
study at a facility selected by the sponsor to enable further analysis of immune responses to 
M1095.  
8.11 
Health Economics 
This study will not collect data for Health Economics.  
 
 
 
 
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9.0 
STATISTICAL ANALYSIS  
Statistical analysis of this study will be the responsibility of the sponsor or its designee.  
Continuous data will be summarized in terms of the number of observations (n); mean; 
standard deviation and/or standard error of the mean, if applicable; median; minimum; and 
maximum. 
Categorical data will be summarized in terms of the number of observations (n), frequency 
count, and percentages. 
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.05 unless otherwise 
stated. 
Any change to the data analysis methods described in the protocol will require an amendment 
ONLY if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be 
described in the clinical study report (CSR). Additional exploratory analyses of the data will 
be conducted as deemed appropriate. Complete details of the planned analyses will be 
documented in the SAP. 
9.1 
Statistical Hypotheses 
The primary endpoint is achievement of an IGA score of 0 or 1 at Week 12, with an IGA 
reduction of at least 2 points from baseline. The proportion of subjects in the Intent to Treat 
(ITT) Analysis Set with an IGA score of 0 or 1 at Week 12 will be used to compare treatment 
arms. The following null hypotheses will be tested at Week 12: 
• 
H1: M1095 30mg q2w x 3, followed by 30mg q4w x 1, is not different from placebo 
with respect to achievement of IGA scores of 0 or 1. 
• 
H2: M1095 60mg q2w x 3, followed by 60mg q4w x 1, is not different from placebo 
with respect to achievement of IGA scores of 0 or 1. 
• 
H3: M1095 120mg q2w x 3, followed by 120mg q4w x 1, is not different from placebo 
with respect to achievement of IGA scores of 0 or 1. 
• 
H4: M1095 120mg q2w x 6 is not different from placebo with respect to achievement 
of IGA scores of 0 or 1. 
The primary analysis method will be performed on the ITT Analysis Set and the treatment 
arms will be compared with the Cochran-Mantel-Haenszel test stratified by prior biologic use 
(yes/no) and body weight stratum (≤90kg, >90kg). Significance for each hypothesis will be 
assessed at the 2-sided 5% level. No adjustment for multiple comparisons will be made. 
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9.2 
Sample Size Determination  
A sufficient number of subjects will be screened, so that a total of approximately 300 subjects 
will be randomized (approximately 50 per treatment group.) 
With this sample size, the study has >99% power to detect a statistically significant difference 
between any treatment arm and placebo in the IGA score of 0 or 1 rate at Week 12, with a two-
sided, unadjusted type I error of 0.05. These calculations assume IGA score of 0 or 1 rates of 
>88% for study drug and ≤7% for placebo.6 As this is a phase 2 study, there will be no 
adjustments for multiplicity.  
Exploratory analyses between the different dose levels of M1095 will also be performed. The 
PASI 100 response rate offers more discriminatory potential for this. Phase 1 data and response 
simulations give a PASI 100 response rate at Week 12 varying from 45 to 72%. With the 
sample size of 50 subjects per group, based on these assumed PASI 100 response rates at Week 
12, the comparison between the highest and lowest M1095 doses has approximately 79% 
power. 
Power calculations have been performed with SAS v.9.4 Proc Power using the methodology 
for a two-group chi square test of equal proportions. 
Randomization will be stratified by prior biologic use (yes, no) and weight (≤90kg, >90kg).  
9.3 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
Enrolled 
All subjects who sign informed consent 
Intent to Treat 
(ITT)  
The Intent to Treat (ITT) population includes all subjects randomly 
allocated to a treatment. Subjects will be analyzed according to 
planned treatment.  
Modified Intent 
To Treat (MITT) 
The Modified Intent to Treat (MITT) population includes all subjects 
in the ITT Analysis Set who receive at least one dose of study drug, 
have a baseline, and at least one post baseline efficacy assessments. 
Subjects will be analyzed according to planned treatment. 
Per-Protocol (PP) 
The Per-Protocol (PP) population includes all subjects in the MITT 
Analysis Set who have no important clinical protocol deviations 
affecting the assessment of efficacy. Membership of the PP Analysis 
Set will be confirmed prior to unblinding the data. Subjects will be 
analyzed according to planned treatment. 
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The primary analysis set for efficacy data will be the ITT Analysis Set.  
The primary analysis will be repeated on the MITT and PP Analysis Sets. Furthermore, 
selected sensitivity analyses will be performed on the ITT Analysis Set, including multiple 
imputation and last-observation carried forward. Safety data will be analyzed using the Safety 
Analysis Set. 
9.4 
Statistical Analyses 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. A comprehensive SAP will provide full details on all planned analyses for this study 
prior to the first interim data analysis.  
The primary analysis is at Week 12 and key secondary analyses are at Week 24. 
9.4.1 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
The primary endpoint is achievement of an IGA score of 0 or 1 at Week 12. 
Response rates of IGA score of 0 or 1 at Week 12 will be used to compare the 
treatment arms. The response rate of IGA score of 0 or 1 at Week 12 is defined 
as the proportion of subjects at Week 12 with an IGA score of 0 or 1 and with 
an IGA reduction from baseline of 2 points or more. Baseline IGA score is the 
last score prior to the first dose of study medication. Any missing IGA score of 
0 or 1 response will be imputed as a non-response. 
The primary analysis will be based on the ITT Analysis Set. The primary 
treatment comparisons will be made using the two-sided Cochran-Mantel-
Haenszel (CMH) test stratified by prior biologic use and body weight stratum. 
Secondary 
The key secondary endpoints are the PASI 75, PASI 90 and PASI 100 at Week 
12. Secondary efficacy and QoL endpoints will be compared between 
randomized treatments in the ITT Analysis Set at each visit up to Week 12 and 
at Weeks 24, 36 and 48 using the CMH test for binary endpoints and for the 
shift from baseline in IGA and an Analysis of Covariance (ANCOVA) model 
Safety 
The Safety population includes all subjects who receive at least one 
dose of study treatment. The Safety population will be analyzed per 
the actual treatment received. 
Pharmacokinetic 
The Pharmacokinetic (PK) population includes all subjects who 
receive at least one dose of M1095 with valid (i.e. not flagged for 
exclusion) PK data and no protocol deviation with an impact on PK. 
The PK population will be analyzed per the actual treatment 
received. 
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for changes from baseline. The ANCOVA model will include treatment, prior 
biologic use and weight stratum as factors and the baseline value as a covariate. 
Descriptive summaries will be provided in tabular and graphical formats by 
treatment and over time. 
Analysis of the primary and key secondary endpoints will also be performed 
using the MITT and the PP populations. The impact of missing data on efficacy 
results will be assessed using multiple imputation, last-observation carried 
forward and worst-case imputation methods.  
Exploratory 
Exploratory analyses of efficacy will be made for subjects who (i) were dose-
escalated at Week 12, and (ii) who stopped treatment following IGA score of 0 
at Week 24. 
For the primary and secondary endpoints, comparisons will be made to placebo (all arms), and 
between the M1095 treatment arms. Dose response and dosing frequency response trend 
testing will be performed involving selected M1095 arms and placebo. No formal statistical 
testing will be done between M1095 treatment arms and secukinumab as the secukinumab arm 
is for reference only. Secukinumab will be compared to placebo using the same methods as the 
primary analysis.  
9.4.2 
Subject Demographics/Other Baseline Characteristics 
All data for background and demographic variables will be listed by treatment group and 
subject. For these parameters summary statistics will be provided by treatment group. 
 
Relevant medical history, current medical conditions, results of laboratory screens, drug tests 
and any other relevant information will be listed by treatment group and subject. 
9.4.3 
Subject Disposition 
All subjects who discontinue from the study will be identified, and the extent of their 
participation in the study will be reported. If known, a reason for their discontinuation will be 
given. 
Subject disposition will be summarized for each treatment period and overall. Reasons for 
discontinuation from the study will be summarized.  
9.4.4 
Treatment Compliance 
Treatment compliance with study drug will be summarized for each treatment period. Subject 
compliance with study drug will be assessed at each visit. A subject will be considered overall 
compliant for each study period if he/she is missing no more than 20% of the expected doses 
and not missing 2 consecutive doses. Proportions of subjects compliant by visit and overall 
compliance will be summarized by treatment groups. 
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9.4.5 
Safety Analyses 
Safety data will be summarized in the Safety Analysis Set by treatment. AEs will be 
summarized for each treatment period separately and overall. Treatment periods are described 
in Section 4.1. No statistical analyses of the safety data are planned. 
9.4.5.1 
Vital Signs 
All vital signs data will be listed by treatment, subject, and visit/time and if ranges are available 
abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics, for 
absolute values and change from baseline, will be provided by treatment and visit/time. 
9.4.5.2 
ECG Evaluations 
All ECG data will be listed by treatment, subject and visit/time, abnormalities will be flagged. 
Summary statistics, for absolute values and change from baseline, will be provided by 
treatment and visit/time. 
9.4.5.3 
Clinical Laboratory Evaluations 
All laboratory data will be listed by treatment, subject, and visit/time and if ranges are available 
abnormalities will be flagged. Summary statistics will be provided by treatment and visit/time. 
9.4.5.4 
Adverse Events 
All information obtained on adverse events will be displayed by treatment and subject. 
Treatment-Emergent AEs (TEAEs) are AEs that emerge while on study treatment, having been 
absent pre-treatment, or that worsen during study treatment relative to the pre-treatment state. 
Serious TEAEs including deaths, TEAEs that led to investigational product discontinuation, 
and TEAEs by maximum severity and relationship to investigational product will be 
summarized by the Medical Dictionary for Regulatory Activities (MedDRA) system organ 
class and preferred term. The number and percentage of subjects with TEAEs will be tabulated 
by body system and preferred term. A subject with multiple AEs within a body system is only 
counted once towards the total of the body system. A subject with multiple AEs within the 
same preferred term is only counted once towards the total of the preferred term. 
AESI will also be presented and summarized. AESI include cytopenias, liver function test 
changes/enzyme elevations, infections, injection-site reactions, allergic/hypersensitivity 
reactions, cerebrocardiovascular events, malignancies, depression, Crohn’s disease and 
ulcerative colitis. Additional adverse events may be identified as being of special interest 
during the study and prior to first unblinding. 
9.4.5.5 
Suicidality and Self-Injurious Behavior 
Suicide-related thoughts and behaviors and self-injurious behavior with no suicidal intent, 
based on the eC-SSRS, will be listed by subject. 
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9.4.5.6 
Previous and Concomitant Therapy 
Previous and concomitant therapies will be listed by treatment group and subject. Concomitant 
medications will be summarized by treatment. 
9.4.6 
Other Analyses  
As possible, subgroup analyses of key efficacy and safety data will be performed by 
geographical region, prior biological use, weight category, gender and geriatric status. 
Detailed description of the subgroup variables and detailed analysis methodology will be 
defined in the SAP. Additional subgroup analyses may be performed as deemed necessary.  
9.4.7 
PK Analyses 
An exploratory population PK analysis may be performed to model M1095 pharmacokinetics. 
The modelling effort should provide guidance about the design of further studies in terms of 
dose and regimen. 
Full details of the PK analysis will be provided either in the SAP, or in a separate PK plan prior 
to the analysis taking place. The population PK analysis will be presented separately from the 
main CSR. 
9.4.8 
Immunogenicity Analyses 
Binding and neutralizing antibodies will be defined by the percentage of subjects with 
antibodies and the titers of antibody. These data will be summarized. 
9.5 
Interim Analyses  
An unblinded interim analysis of complete 12-week data will occur at the end of the Week 12 
period, while the study is still ongoing. This will be managed by an independent DMC and 
statistical analysis group to preserve the blinding. This data will be shared with firewalled 
individuals who are not directly involved in the conduct of the study.  
A second interim analysis will occur at the completion of the Week 24 period. All investigators 
and subjects will remain blinded to treatment assignments until the last subject completes the 
study and the final database lock occurs. Once the second interim database lock has occurred 
after Week 24, the study statistician, statistical programmers, and designated sponsor team 
members will be unblinded to perform analysis of key study endpoints.   
The study will not be terminated early on the basis of positive efficacy after the first or the 
second interim database locks. 
Information that may unblind the study during the analyses will not be reported to study sites 
or the blinded study team until the study has been unblinded. All investigators and subjects 
will remain blinded to treatment assignments until the last subject completes the study and the 
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final database lock occurs. Once the second interim database lock has occurred after Week 24, 
the sponsor study team will be unblinded.  
The SAP will specify the analyses to be performed and the tables, figures and listings (TFLs) 
to be generated at each interim analysis. The SAP will be finalized prior to the first unblinding.  
9.5.1 
Data Monitoring Committee (DMC) 
An independent Data Monitoring Committee (DMC) will be established to closely monitor the 
safety and tolerability data throughout the study and review interim analyses during the study. 
The DMC will be operational prior to enrolment of the first subject into the study. The 
composition and operation of the DMC will be described in a DMC charter. The charter will 
also detail how the communication between the DMC and the sponsor will be firewalled to 
preserve the blinding and integrity of the study.  
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10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
o Applicable International Council for Harmonization (ICH) Good Clinical Practice 
(GCP) Guidelines 
o Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IRB/IEC approval before implementation 
of changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study subjects.  
• The investigator will be responsible for the following: 
o Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
o Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
o Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, European Clinical Trials Directive 2001/20/EC, and all other applicable 
local regulations. 
10.1.2 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the study and for 1 year 
after completion of the study. 
10.1.3 
Informed Consent Process 
• The investigator or his/her representative will explain the nature of the study to the 
subject or his/her legally authorized representative and answer all questions regarding 
the study.  
• Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that 
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meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, 
and the IRB/IEC or study site.  
• The medical record must include a statement that written informed consent was 
obtained before the subject was enrolled in the study and the date the written consent 
was obtained. The authorized person obtaining the informed consent must also sign the 
ICF. 
• Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
• Separate ICFs will be used to document agreement for skin evaluation (including 
assessments of genomic biomarkers) should this be required as per Section 8.4.2, and 
to document agreement to collect information from a study subject’s partner in case of 
pregnancy.  
• A separate ICF may also be used to document agreement for HIV testing, depending 
on local requirements. 
• A separate ICF may also be used to document agreement for use of a subject expense 
reimbursement system, depending on local requirements. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.  
10.1.4 
Data Protection 
• Subjects will be assigned a unique identifier by the sponsor. Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred.  
• The subject must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the subject.  
• The subject must be informed that his/her medical records may be examined by study 
monitors, Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.1.5 
Study Steering Committee  
A Study Steering Committee will be utilized for the study. Membership will include an overall 
Principal Investigator as well as regional lead investigators. The scope of the Study Steering 
Committee will be described in its applicable Charter. 
10.1.6 
Dissemination of Clinical Study Data 
Key design elements of this protocol will be made publicly available via the European Clinical 
Trials Database (EudraCT) and www.ClinicalTrials.gov. On study completion and finalization 
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of the CSR, the results of this study will be either submitted for publication and/or made 
publicly available via the EudraCT database and www.ClinicalTrials.gov.  
10.1.7 
Data Quality Assurance 
• All subject data relating to the study will be recorded on an eCRF (printed pages are 
acceptable only if the eCRF is unavailable) unless transmitted to the sponsor or 
designee electronically (e.g., laboratory data). The investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF.  
• The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
• The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements.  
• Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 15 years after study completion unless local 
regulations or institutional policies require a longer retention period. No records may 
be destroyed during the retention period without the written approval of the sponsor. 
No records may be transferred to another location or party without written notification 
to the sponsor.  
10.1.8 
Source Documents 
• Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site. 
• Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records. Also, 
current medical records must be available. 
• Definition of what constitutes source data can be found in the Source Data Agreement 
agreed with each investigator prior to site initiation. 
10.1.9 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
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completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the investigator 
• Discontinuation of further study intervention development 
Study recruitment will be stopped at a site when the total requested number of subjects for the 
study has been obtained, irrespective of the specific site’s inclusion number. Investigators will 
be informed when recruitment is to cease. 
When study analyses are complete the investigators will receive information about the 
treatment allocation for the subjects randomised at their respective sites. 
The sponsor may stop the study prematurely after consultation with the investigator, e.g., if the 
subject recruitment is so slow that the study cannot be completed within a reasonable time 
frame. Such premature termination/suspension of the study will be notified to Regulatory 
Authorities and IECs/IRBs as required. 
 
10.1.10 
Publication Policy 
• The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments.  
• The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
 
 
 
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10.2 
Appendix 2: Clinical Laboratory Tests 
• The tests detailed in Table 2 will be performed by the central laboratory.  
• Local laboratory results are only required if central laboratory results are not available 
in time for either study intervention administration and/or response evaluation. If a 
local sample is required, it is important that a sample for central analysis is obtained at 
the same time. Additionally, if local laboratory values are used to make either a study 
intervention decision or response evaluation, the values must be entered into the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5.0 of the protocol. 
• Additional tests may be performed at any time during the study as deemed necessary 
by the investigator or required by local regulations. 
• Review of each laboratory report must be documented by an investigator.  
Table 2: Protocol-Required Safety Laboratory Assessments 
Hematology 
• 
Hemoglobin 
• 
Hematocrit 
• 
Red Blood Cell (RBC) count 
• 
White Blood Cell (WBC) count with differential 
o 
Lymphocytes 
o 
Monocytes 
o 
Neutrophils 
o 
Bands 
o 
Eosinophils 
o 
Basophils 
• 
Platelets 
• 
ESRA 
Chemistry 
• 
Albumin 
• 
Alkaline phosphatase 
• 
ALT 
• 
AST 
• 
Total CO2 
• 
Total bilirubin 
o 
Direct bilirubin (if Total bilirubin is out of range) 
• 
Urea 
• 
Calcium 
• 
Chloride 
• 
Creatinine 
• 
Glucose 
• 
Potassium 
• 
Total protein 
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• 
Sodium 
• 
Plasma GlucoseA 
• 
High sensitivity CRPA 
• 
LipidsA 
o 
Total cholesterolA 
o 
LDLA 
o 
HDLA 
o 
Total cholesterol to HDL ratioA 
o 
TriglyceridesA 
Urinalysis 
• 
Blood 
• 
White blood cells 
• 
Glucose 
• 
Protein 
• 
Ketones 
• 
pH 
Serology 
• 
Anti-HBVB 
• 
Anti-HCVB 
• 
Anti-HIVB 
• 
QuantiFERON®-TB GoldC 
Pregnancy Test 
• 
hCG (in serum)D  
• 
hCG (in urine)D 
 
A – Additional tests performed at Weeks 0 (randomization), 12, 24, 36 and 48. This must be a FASTING blood 
sample. ESR will be performed at the study site using a kit provided by the central laboratory.  
 
B – Screening only. See Section 10.5, Appendix 5 for details. 
 
C – Screening only. Sample to be sent to central or local laboratory. 
 
D – Pregnancy test in serum at Screening only, unless subsequent local urine pregnancy test is positive, in which 
case a central laboratory serum test should be repeated (See Section 10.4, Appendix 4).  
 
 
 
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10.4 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information 
Contraceptive guidance is given as per the Clinical Trial Facilitation Group recommendations 
related to contraception and pregnancy testing in clinical trials.24 
Women are considered not of child bearing potential if they are surgically sterile or post-
menopausal defined as 12 months of natural (spontaneous) amenorrhea with an appropriate 
clinical profile (e.g. age appropriate, history of vasomotor symptoms).  
Highly effective contraception must be used by all female subjects considered women of child 
bearing potential throughout the study and for 12 weeks following the last dose of study drug.  
 Highly effective contraception is defined as:  
i. Total abstinence: When this is in line with the preferred and usual 
lifestyle of the subject. [Periodic abstinence (e.g. calendar, ovulation, 
symptothermal, post-ovulation methods) and withdrawal are not 
acceptable methods of contraception]. 
ii. Female sterilization: have had a surgical bilateral oophorectomy (with 
or without hysterectomy) or tubal ligation at least six weeks before 
taking study treatment. In case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow up 
hormone level assessment 
iii. Male partner sterilization (with the appropriate post-vasectomy 
documentation of absence of sperm in the ejaculate). (For female 
subjects on the study, the vasectomized male partner should be the sole 
partner for that subject). 
iv. Use of established oral, intravaginal, transdermal, injectable or 
implantable hormonal methods of contraception associated with 
inhibition of ovulation.  
v. Intrauterine device (IUD) or intrauterine hormone-releasing system 
(IUS). 
Male subjects must also use contraception throughout the study and for 12 weeks following 
the last dose of study drug. The following methods of contraception are permitted for male 
study subjects. 
i. Condom 
ii. Sterilization (with the appropriate post-vasectomy documentation of 
absence of sperm in the ejaculate). 
iii. Contraception taken by female partners if considered women of child 
bearing potential.  
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At each study visit, female and male subjects will be reminded that they must follow the 
study’s contraceptive guidance. This includes the final study visit, either Week 52 or the 
Early Discontinuation – Visit 2, when subjects will be reminded that they must follow the 
study’s contraceptive guidance for at least 4 more weeks, and that they should inform the 
investigator immediately should they or their partner become pregnant in this time.  
Pregnancy Testing 
• 
Women of child bearing potential should only be included in the study after a confirmed 
menstrual period and a negative highly sensitive serum pregnancy test, performed by the 
study’s central laboratory as part of study screening. 
• 
Local pregnancy testing should be performed at the baseline (randomization) visit, and at 
Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, plus the Early Discontinuation 
Visit. Pregnancy testing will also be performed whenever a menstrual cycle is missed or 
when pregnancy is otherwise suspected. A urine dipstick test will be performed locally by 
the study site personnel.  
• 
If at any stage, a local pregnancy test is positive, a highly sensitive serum pregnancy test 
should be performed via the study’s central laboratory.  
Collection of Pregnancy Information: 
Male subjects with partners who become pregnant  
• 
The investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study.  
• 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor’s designee within 24 hours of learning of the partner’s pregnancy. 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure.  
Female subjects who become pregnant  
• 
The investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the sponsor within 24 hours of learning of a subject's pregnancy. 
The subject will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the subject and the neonate and the information will 
be forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 
to 8 weeks beyond the estimated delivery date. Any termination of pregnancy will be 
reported, regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
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• 
Any female subject who becomes pregnant while participating in the study will 
discontinue study drug.  
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion 
is always considered to be an SAE and will be reported as such. Any post-study pregnancy 
related SAE considered reasonably related to the study intervention by the investigator will be 
reported to the sponsor as described in Section 8.5.4. While the investigator is not obligated to 
actively seek this information in former study subjects, he or she may learn of an SAE through 
spontaneous reporting.  
 
 
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Based on this scale, a subject will be eligible to participate in the study if the subject has an 
IGA score at baseline of 3 or 4. 
Based on this scale, a subject will be considered as an IGA 0 or 1 responder if the subject 
achieves a score of 0 or 1. 
10.6.2 
Total Body Surface Area (BSA) and Psoriasis Area and Severity Index 
(PASI) 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of 
areas affected, including head, trunk, upper limbs and lower limbs (see below for PASI 
assessment).  
The site will initially record assessments on paper and will then enter the data into the eCRF, 
which will auto-calculate the PASI score (no manual PASI calculations will be required by the 
site). 
Rounding should occur (e.g. 9.49% = 9 and 9.5% = 10) except in any instance where the 
percentage is just above 0 (i.e. 0.25% should round up to 1, not down to 0).  
A PASI score will be derived as indicated in Table 4.11, 12 The head, trunk, upper limbs and 
lower limbs are assessed separately for erythema, thickening (plaque elevation, induration), 
and scaling (desquamation). The average degree of severity of each sign in each of the four 
body regions is assigned a score of 0-4. The area covered by lesions on each body region is 
estimated as a percentage of the total area of that particular body region. Further practical 
details help the assessment: 
• The neck is assessed as part of the head. 
• The axillae and groin are assessed as part of the trunk. 
• The buttocks are assessed as part of the lower limbs. 
• When scoring the severity of erythema, scales should not be removed. 
 
 
 
 
 
 
 
 
 
 
 
 
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The investigator is only responsible for collecting the components or scoring signs and total 
regional area. PASI calculations, including changes over time will be calculated via the PASI 
Score eCRF.  
Based on PASI, to be eligible a subject must have a score of 12 or more at baseline. 
Based on total BSA, to be eligible, a subject must have 10% or more total BSA involved at 
baseline. 
Definitions of efficacy variables based on PASI 
The following definitions are used in this study, see Committee for Medicinal Products for 
Human Use (CHMP) guidelines for psoriasis.8 
• PASI 75 response: subjects achieving ≥ 75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders 
• PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score 
• PASI 100 response / remission: complete clearing of psoriasis (PASI=0) 
• Relapse: when the achieved maximal PASI improvement from baseline is reduced by 
>50% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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10.7 
Appendix 7: Abbreviations 
AE 
 
 
Adverse Event 
AESI  
 
Adverse Event of Special Interest 
ALT 
 
 
Alanine Aminotransferase 
ANC  
 
Absolute Neutrophil Count 
ANCOVA 
 
Analysis of Covariance 
AST 
 
 
Aspartate Aminotransferase 
AUC  
 
Area Under the Curve 
BSA  
 
Body Surface Area 
Cmax  
 
Maximum Concentration 
CFR 
 
 
Code of Federal Regulations 
CIOMS 
 
Council for International Organizations of Medical Sciences 
CMH  
 
Cochran-Mantel-Haenszel  
CONSORT 
 
Consolidated Standards of Reporting Trials 
CRO  
 
Contract Research Organization 
CRP 
 
 
C-Reactive Protein 
CS 
 
 
Corticosteroids 
CSR 
 
 
Clinical Study Report 
CTCAE 
 
Common Terminology Criteria for Adverse Events 
CXR  
 
Chest X-Ray 
D/C 
 
 
Discontinuation 
DLQI  
 
Dermatology Life Quality Index 
DMC  
 
Data Monitoring Committee 
DNA  
 
Deoxyribonucleic Acid 
ECG  
 
Electrocardiogram 
eCRF  
 
Electronic Case Record Form 
eC-SSRS 
 
Electronic Columbia Suicide Severity Rating Scale 
EMA  
 
European Medicines Agency 
EQ-POS 
 
Euro-Quality of Life Questionnaire for Psoriasis 
ESR 
 
 
Erythrocyte Sedimentation Rate 
EudraCT 
 
European Clinical Trials Database 
FDA  
 
Food and Drug Administration 
FSH 
 
 
Follicle Stimulating Hormone 
GCP  
 
Good Clinical Practice 
HBV  
 
Hepatitis B Virus 
hCG 
 
 
Human Chorionic Gonadotropin 
HCV  
 
Hepatitis C Virus 
HDL  
 
High Density Lipoprotein 
HIPAA 
 
Health Insurance Portability and Accountability Act 
HIV 
 
 
Human Immunodeficiency Virus 
ICF 
 
 
Informed Consent Form 
ICH 
 
 
International Council for Harmonization 
IEC 
 
 
Independent Ethics Committee 
IGA 
 
 
Investigator’s Global Assessment 
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IgG 
 
 
Immunoglobulin G 
IL 
 
 
Interleukin 
IMP 
 
 
Investigational Medicinal Product 
IRB 
 
 
Institutional Review Board 
IRT 
 
 
Interactive Response Technology 
ITT 
 
 
Intent to Treat 
IUD 
 
 
Intrauterine Device 
IUS 
 
 
Intrauterine System 
IV 
 
 
Intravenous 
LDL 
 
 
Low Density Lipoprotein 
MedDRA 
 
Medical Dictionary for Regulatory Activities 
MITT  
 
Modified Intent to Treat 
PASI  
 
Psoriasis Area and Severity Index 
PFS 
 
 
Pre-Filled Syringe 
PHQ-8  
 
Patient Health Questionnaire-8 
PK 
 
 
Pharmacokinetics 
PP 
 
 
Per Protocol 
PRO  
 
Patient Reported Outcomes 
PUVA  
 
Photochemotherapy (Psoralens and UVA) 
QoL 
 
 
Quality of Life 
q2w 
 
 
Every 2 weeks 
q4w 
 
 
Every 4 weeks 
q8w 
 
 
Every 8 weeks 
RBC  
 
Red Blood Cell 
SAE 
 
 
Serious Adverse Event 
SAP 
 
 
Statistical Analysis Plan 
SF-36  
 
Short-Form 36 
SmPC  
 
Summary of Product Characteristics 
SoA 
 
 
Schedule of Activities 
sPGA  
 
Static Physician’s Global Assessment 
SUSAR 
 
Suspected Unexpected Serious Adverse Reaction 
TB 
 
 
Tuberculosis 
TEAE  
 
Treatment Emergent Adverse Event 
TNF 
 
 
Tumour Necrosis Factor 
ULN  
 
Upper Limit of Normal 
UV 
 
 
Ultraviolet 
UVA  
 
Ultraviolet A (longwave) 
UVB  
 
Ultraviolet B (shortwave) 
VAS  
 
Visual Analogue Scale 
WBC  
 
White Blood Cell 
WFI 
 
 
Water for Injection 
 
 
 
 
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10.8 
Appendix 8: Protocol Amendment History 
 
Amendment 
No. 
Protocol 
version no. 
Date issued 
Details of changes made 
02 
3.0 
inc. CZE-1 
16-Oct-2018 
• Change of office address for 
Avillion LLP 
• Clarification of eligibility 
regarding tuberculosis, and 
permission of re-screening if 
subjects become eligible after 
instigating treatment of latent TB 
• Creatinine clearance may be 
measured via 24-hour urine 
collection, in addition to 
calculation via Cockcroft-Gault 
• FOR CZECH REPUBLIC ONLY 
Exclusion criterion 4g amended to 
exclude subjects with a calculated 
creatinine clearance (via Cockcroft 
Gault) of <60mL/min 
• Exclusion criterion 13 amended to 
include suicidal behavior 
• Clarification of chronic drug abuse 
and IV drugs 
• Exclusion criterion 15 amended to 
clarify the requirement for highly 
effective contraceptive methods in 
women of child bearing potential 
• New exclusion criterion (18) to 
capture requirements for male 
contraception 
• Clarification of PASI endpoints 
• Addition of total BSA to secondary 
endpoints 
• Clarification of IGA endpoints 
• Urine pregnancy test every 4 
weeks 
• Updates to systemic and topical 
prior and prohibited treatments for 
psoriasis 
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AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
 
• Consideration of subject’s response 
at Week 24 and benefit from 
participating in study 
• Clarification that male sterilization 
is a permitted form of 
contraception in male subjects 
• Clarification on use of 
cannabis/marijuana 
• Clarification on release of 
randomization codes for PK 
analysis 
• Efficacy assessments to be 
recorded on paper, and clarification 
of who will perform assessments 
and rounding rules 
• Correction of the null hypothesis 
H4 and clarification of the other 
null hypotheses 
• Update to the statistical methods 
for the secondary endpoints 
• Clarification of visits for which 
treatment comparisons will be 
made 
• Clarification of unblinding at Week 
24 to allow analysis of key study 
endpoints 
• Update to use CTCAE Version 5.0 
• Addition of a separate ICF, per 
local requirements, to agree to the 
use of a subject expense 
reimbursement system. 
• Clarification at Week 52 regarding 
contraception for the next 4 weeks 
• Clarification of requirement to 
capture overdose/medication errors 
on AE eCRF 
• Typos and consistency in wording 
CZE-1 
2.0 
31-Aug-2018 
• Exclusion criterion 4g amended to 
exclude subjects with a calculated 
creatinine clearance (via Cockcroft 
Gault) of <60mL/min 
• Exclusion criterion 15 amended to 
clarify the requirement for highly 
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Page 100 of 103 
AV002 – Final protocol, Version 3.0, incorporating CZE-1, dated 16 October 2018 
 
effective contraceptive methods in 
women of child bearing potential 
• New exclusion criterion (18) to 
capture requirements for male 
contraception 
• Clarification that male sterilization 
is a permitted form of 
contraception in male subjects 
01 
2.0 
03-Apr-2018 
• www.ClinicalTrials.gov NCT 
number added 
• Co-ordinating Investigators added  
• Clarify the method used to blind 
injections to study subjects  
• ECG performed during Screening, 
and not at Week 0 
• HIV test added at Screening 
• Clarify the reconstitution of 30mg 
dose  
• ESR performed at study site using 
a kit provided by central laboratory 
• Clarify that there will be separate 
ICFs for skin evaluation and 
pregnant partners, and that there 
may be a separate ICF for HIV 
testing 
 
 
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Protocol Number: AV002                     CONFIDENTIAL               M1095 phase 2b psoriasis study 
 
 
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11.0 
REFERENCES 
1. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of 
Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology 
of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013 
Feb; 133 (2): 377–85.  
2. Bartlett HS and Million RP. Targeting the IL-17-T(H)17 pathway. Nat Rev Drug 
Discov. 2015 Jan; 14(1):11-2. 
3. Wasilewska A, Winiarska M, Olszewska M, Rudnicka L; Interleukin-17 inhibitors. A 
new era in treatment of psoriasis and other skin diseases. Postepy Dermatol Alergol. 
2016 Aug; 33(4):247-52. 
4. Ablynx website, accessed 27feb2017. http://www.ablynx.com/technology-
innovation/understanding-nanobodies/ 
5. 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.  
6. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/cosenty
x.pdf  
7. https://ec.europa.eu/health/documents/community-
register/2015/20150115130444/anx 130444 en.pdf 
8. EMA guidance: GUIDELINE ON CLINICAL INVESTIGATION OF MEDICINAL 
PRODUCTS INDICATED FOR THE TREATMENT OF PSORIASIS. 
EMEA/CHMP/EWP/2454/02. 
9. http://www.consort-statement.org/ 
10. Langley RG, Feldman SR, Nyirady J, van de Kerkhof P, Papavassilis C; The 5-point 
Investigator’s Global Assessment (IGA) Scale: A modified tool for evaluating plaque 
psoriasis severity in clinical trials. J Dermatolog Treat. 2015 Feb; 26(1):23-31. 
11. Fredriksson T, Pettersson U; Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica. 1978; 157(4):238-44. 
 
12. Weisman S, Pollack CR, Gottschalk RW; Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat. 2003 Sep, 
14(3):158-65. 
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13. Finlay AY, Khan GK; Dermatology Life Quality Index (DLQI) – a simple practical 
measure for routine clinical use. Clin Exp Dermatol. 1994 May; 19(3):210-6.  
14. Ware JE, Brook RH, Williams KN, et al.; Conceptualisation and Measurement of 
Health for Adults in the Health Insurance Study, Vol 1. Model of Health and 
Methodology, 1980 Santa Monica, CA. Rand Corp 
15. Garratt AM, Ruta DA, Abdalla MI, Buckingham JK, Russell IT; The SF36 health 
survey questionnaire: an outcome measure suitable for routine use within the NHS? 
BMJ. 1993 May 29; 306(6890):1440-4.  
16. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X; 
Development and preliminary testing of the new five-level version of EQ-5D (EQ-
5D-5L). Qual Life Res. 2011 Dec; 20(10):1727-36. 
17. Swinburn P, Lloyd A, Boye KS, Edson-Heredia E, Bowman L, Janssen B; 
Development of a disease-specific version of the EQ-5D-5L for use in patients 
suffering from psoriasis: lessons learned from a feasibility study in the UK. Value 
Health. 2013 Dec; 16(8):1156-62. 
18. Mundt JC, Greist JH, Gelenberg AJ, Katzelnick DJ, Jefferson JW, Modell JG; 
Feasibility and validation of a computer-automated Columbia-Suicide Severity Rating 
Scale using interactive voice response technology. J Psychiatr Res. 2010 Dec; 
44(16):1224-8.  
19. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier 
GW, Melvin GA, Greenhill L, Shen S, Mann JJ; The Columbia-Suicide Severity 
Rating Scale: initial validity and internal consistency findings from three multisite 
studies with adolescents and adults. Am J Psychiatry. 2011 Dec; 168(12):1266-77. 
20. Mundt JC, Greist JH, Jefferson JW, Federico M, Mann JJ, Posner K; Prediction of 
suicidal ideation and behaviour ascertained by the electronic Columbia-Suicide 
Severity Rating Scale. J Clin Psychiatry. 2013 Sep; 74(9):887-93. 
21. Kroenke K, Spitzer RL; The PHQ-9: a new depression diagnostic and severity 
measure. Psychiatr Ann. 2002 Sep; 32(9);509-15.  
22. Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH; The PHQ-8 
as a measure of current depression in the general population. J Affect Disord. 2009 
Apr; 114(1-3):163-73.  
23. https://evs.nci.nih.gov/ftp1/CTCAE/About.html 
24. http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
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12.0 
SIGNATURE OF INVESTIGATOR  
PROTOCOL TITLE: A phase 2b randomized, double-blind, placebo controlled, multi-center 
12-week study with an additional 40-week follow-up assessment of efficacy, safety and 
tolerability of M1095 in subjects with moderate to severe chronic plaque-type psoriasis. 
PROTOCOL NO: 
AV002  
This protocol is a confidential communication of Bond Avillion 2 Development LP. I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol. I will 
also work consistently with the ethical principles that have their origin in the Declaration of 
Helsinki and that are consistent with good clinical practices and the applicable laws and 
regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval 
from Bond Avillion 2 Development LP. 
 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the 
name/address of the center in which the study will be conducted. Return the signed copy to the CRO. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
 
Signature 
 
Title  
 
 
 
 
 
 
Printed Name 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name/Address of Center 
 
 
 
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