A Phase II, Multicenter, Double-blind, Placebo-controlled, Efficacy and Safety Trial of Two Oral Doses (150 mg Bid / 300 mg Bid) of MP1032 in Male and Female Patients With Moderate-to-Severe Chronic Plaque Psoriasis
Phase: PHASE2
Conditions: Psoriasis
Sponsor: MetrioPharm AG



Appendix 16.1.1 
 
MP1032-CT04 
 
 
 
 
Contents 
 
 
 
Clinical trial protocol, V1.0 dated 22SEP2017  
 
Amendment 1 dated 19OCT2018 to clinical trial protocol version 1 from 22SEP2017 
 
Clinical trial protocol, V2.0 dated 19OCT2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CCI

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Responsible person for SAE notifications: 
 
 
 
 
 
 
 
 
SAE reporting to:  
  
 
 
 
PPD, CCI
CCI

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Table of Content 
Tables ................................................................................................................................. 12 
1. 
Abbreviations ................................................................................................................ 13 
2. 
Introduction ................................................................................................................... 15 
3. 
Risk-benefit evaluation ................................................................................................... 16 
3.1 
Stress/risks due to trial procedures ........................................................................ 16 
3.2 
Stress/risks due to the investigational medicinal product (IMP) ............................... 17 
4. 
Trial objectives/endpoints ............................................................................................... 19 
5. 
Investigational plan ........................................................................................................ 21 
5.1 
Overall trial design and plan - description ............................................................... 21 
5.2 
Discussion of trial design, including the choice of control groups ............................. 21 
5.3 
Selection and discontinuation/withdrawal of patients .............................................. 22 
5.3.1 Selection of patients ................................................................................... 22 
5.3.2 Inclusion criteria ......................................................................................... 23 
5.3.3 Exclusion criteria ........................................................................................ 24 
5.3.4 Restrictions during the clinical trial .............................................................. 27 
5.3.5 Removal of patients from therapy or assessment ........................................ 27 
5.3.6 Definition of end of trial ............................................................................... 28 
5.4 
Treatments ........................................................................................................... 29 
5.4.1 Treatments to be administered (manner and dose selection) ....................... 29 
5.4.2 Identity of investigational medicinal products ............................................... 30 
5.4.3 Assignment of treatments and randomization .............................................. 31 
5.4.4 Blinding and Breaking the Blind .................................................................. 31 
5.4.5 Prior and concomitant therapy .................................................................... 32 
5.4.6 Treatment compliance ................................................................................ 33 
5.5 
Efficacy and safety variable(s) ............................................................................... 33 
5.5.1 Procedures ................................................................................................ 33 
5.5.2 Measurement of safety parameters ............................................................. 39 
5.5.3 Vital signs .................................................................................................. 40 
5.5.4 Smoking and alcohol consumption .............................................................. 40 
5.5.5 Physical examination ................................................................................. 41 
5.5.6 Appropriateness of assessments ................................................................ 41 
6. 
Data analysis and statistics ............................................................................................ 42 
6.1 
Generation of data base ........................................................................................ 42 
6.2 
Analysis sets and type of analysis ......................................................................... 42 
6.3 
Hypotheses .......................................................................................................... 43 
6.4 
Rationale for the sample size ................................................................................ 43 
6.5 
Statistical methods ................................................................................................ 43 
6.5.1. Efficacy analyses ....................................................................................... 44 
6.5.2. Safety analyses ......................................................................................... 44 
6.5.3. Other analyses........................................................................................... 45 

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6.6 
Handling of dropouts and missing data .................................................................. 45 
6.7 
Identification of source data ................................................................................... 45 
7. 
Adverse events.............................................................................................................. 46 
7.1 
Evaluation of adverse events ................................................................................. 46 
7.2 
Definition of serious and nonserious adverse events .............................................. 47 
7.3 
Reporting/documentation of adverse events........................................................... 48 
7.3.1 Reporting of adverse events ....................................................................... 48 
7.3.2 Reporting of serious adverse events ........................................................... 50 
7.4 
Pregnancies ......................................................................................................... 51 
8. 
Case report form (CRF), documentation and archiving .................................................... 51 
8.1 
Primary source documents .................................................................................... 52 
9. 
Statutory regulations and GCP ....................................................................................... 53 
9.1 
Ethics committee/competent authorities ................................................................. 54 
9.2 
Insurance ............................................................................................................. 54 
9.3 
Patient instruction and consent forms .................................................................... 54 
9.4 
Data protection ..................................................................................................... 55 
9.5 
Termination of participation ................................................................................... 55 
9.6 
Quality control (Trial monitoring) ............................................................................ 56 
9.7 
Quality assurance ................................................................................................. 56 
9.8 
Handling of investigational medicinal products ....................................................... 57 
10. Trial administrative structure/responsibilities ................................................................... 58 
11. Literature ....................................................................................................................... 59 
Appendix A Trial flow chart 
Appendix B PASI 

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Tables  
 
Table 1: Objectives and endpoints 
Table 2: Prior treatment  
Table 3: Details of the IMPs  
Table 4: Laboratory parameter per visit 
Table 5: Vital signs ranges 
Table 6: Trial administrative structure/responsibilities 
 
 
 

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1. 
Abbreviations 
ADP 
 
Adenosine diphosphate ribose 
ADR  
adverse drug reaction 
AE 
 
adverse event 
ALT 
 
alanine aminotransferase 
AMG  
German drug law (Arzneimittelgesetz)  
AST   
aspartate aminotransferase 
AUC  
area under the curve 
BfArM 
Federal institute for drugs and medical devices (Bundesinstitut fuer Arzneimittel und 
Medizinprodukte) 
BMI 
 
body mass index 
CA 
 
competent authority 
CMH  
Cochran-Mantel-Haenszel 
CRF 
 
case report form 
EC 
 
ethics committee 
ENT 
 
Ear nose throat 
EoS 
 
End of study 
EoT 
 
end of treatment 
FAS 
 
full analysis set 
(c)-fms  
colony-stimulating factor-1 receptor 
GCP  
good clinical practice 
GMP  
good manufacturing practice 
GOT  
glutamic oxaloacetic transaminase 
GPT 
 
glutamic pyruvic transaminase 
HIV 
 
human immunodeficiency virus 
HRT 
 
hormone replacement therapy 
IB 
 
investigator's brochure 
ICH 
 
international conference on harmonisation 
IL-6 
 
interleukin-6 
IMP 
 
investigational medicinal product 
IMPD  
investigational medicinal product dossier 
ITT 
  
intent-to-treat 
IWRS  
Interactive Web Response Systems 
MCH  
mean corpuscular hemoglobin 
MCHC  
mean corpuscular hemoglobin concentration 
MCV  
mean corpuscular volume 
MedDRA medical dictionary for regulatory activities 
PARP-1 
poly(adenosine diphosphate [ADP]-ribose) polymerase 1 
PP 
 
per-protocol 
PT 
 
preferred term 
PV 
 
Pharmacovigilance 
RBC  
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis system 
SES 
safety evaluation set 
SGK-2 
serine / threonine-protein kinase 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 

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TACE 
metalloprotease TNF-α converting enzyme 
TEAE 
treatment emergent adverse event 
TMF 
 
trial master file 
TNF-α  
Tumor Necrosis Factor α 
VCS 
 
valid cases set 
WBC  
white blood cell 
WCBP  
women of childbearing potential 
WHO  
world health organization 

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2. 
Introduction 
MP1032 is a small-molecule macrophage modulator currently not available as a registered or 
approved medicinal product within the borders of the European economic area, the United States, 
or Japan. Experimental data have shown that MP1032 can inhibit inflammation by reducing Tumor 
Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) [1]. MetrioPharm AG is developing MP1032 as 
an anti-inflammatory compound. The first target indication is psoriasis. 
Psoriasis is a relatively common skin condition, affecting 1.5 to 3% of the general population in 
Europe [2]. Psoriasis can have a particularly negative effect on quality of life, affecting a sufferer’s 
physical, social, and psychological functioning so the need for effective therapies is high. 
Psoriasis is characterized by outbreaks of skin inflammation interspersed by varying periods of 
remission. The underlying mechanisms of the inflammatory flares in psoriasis are poorly 
understood, but the therapeutic potency of anti-TNF- α and anti-IL-17 biologics is evidence of 
immune modulation’s potential to reduce disease severity [1]. 
However, antibody-based biologics therapies are not optimal therapies for life-long treatment of 
psoriasis, due to decreasing efficacy over time and relatively high costs. Furthermore, the use of 
immune-suppressive drugs, such as methotrexate, cyclosporine, or anti-TNF-α/IL-12/IL-17/ IL-23 
biologics increases the risk of opportunistic infections and/or requires regular laboratory checks 
on blood and liver function [1]. 
MP1032 has been shown to reduce TNF-α and IL-6 levels in vitro (human peripheral blood 
mononuclear cells and differentiated human promyelocytic leukemia cells), and in vivo, and its 
anti-inflammatory potential has been shown in mouse and rat arthritis models. Other anti-
inflammatory compounds usually exhibit immune-suppressive effects resulting in an increased 
vulnerability to infections. MP1032, on the other hand, has shown an anti-infective potential in 
animal infection models. 
The mechanism of action is thought to be mediated by MP1032’s partial inhibition of the enzyme 
poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP-1), the kinases human Aurora-B, 
human Aurora-C, serine / threonine-protein kinase (SGK-2), tyrosine kinase (colony-stimulating 
factor-1 receptor [c-fms / FMS], and the metalloprotease TNF-α converting enzyme (TACE, also 
known as ADAM17).  
As a multi-target small-molecule macrophage modulator, MP1032 seems to avoid the problems 
of tolerance and reduced long-term efficacy that biologics have. An important potential safety 
advantage of MP1032 lies in the observation from animal models that the compound reduces 
rather than increases susceptibility to bacterial and viral infections. This may be due to the fact 
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MetrioPharm considers these molecular and safety characteristics along with the ease of an oral 
therapy over topical therapies as strong arguments for MP1032 to become an effective therapy 
option in moderate-to-severe psoriasis, where topical agents are not effective enough or too 
tedious for patients to apply them regularly. 
MP1032 has been assessed in a phase I first-in-man clinical trial. In part 1 of this trial (single-
ascending doses), 12 volunteers were administered 50 to 600 mg MP1032. One mild adverse 
drug reaction (ADR) of “headache” was classified as related to the investigational medicinal 
product (IMP) and was reported after treatment with 50 mg MP1032. In part 2 of the clinical trial, 
general safety and tolerability of MP1032 were assessed in multiple ascending doses. No ADRs 
were reported in part 2, in which the volunteers received 2 × 100 mg per day and 2 × 300 mg per 
day at 12-hour intervals for 7 consecutive days. 
Subsequently, an exploratory, double-blind, parallel phase IIa trial to evaluate the safety, 
pharmacokinetics and efficacy of orally administered MP1032 in patients with moderate to severe 
chronic plaque psoriasis was performed. A total of 44 patients were randomized with a 1:1 ratio 
to either receiving 100 mg MP1032 twice daily or placebo for 42 days. The findings of that trial 
shows that after only six weeks of treatment, there is a clinically meaningful response in patients 
who entered the trial with a PASI score of 10-20 and achieved appropriate MP1032 exposure 
values. As MP1032 is well tolerated, further studies using higher doses of MP1032 and longer 
treatment durations need to be conducted to fully evaluate the efficacy of MP1032 for the 
treatment of moderate to severe psoriasis. 
Further details can be found in the Investigator's Brochure (Edition 5, September 2017), which 
contains comprehensive information on the IMP [3]. See Section 5.1 for details concerning the 
design of the current trial and section 5.2 for justification of the design of this trial. 
3. 
Risk-benefit evaluation 
3.1 
Stress/risks due to trial procedures 
The noninvasive procedures (clinical assessments and photographic documentation) do not pose 
a risk or stress for the patients.  
The blood sampling procedure poses the same very small risk as normally associated with this 
procedure (e.g. infection, bleeding into the surrounding tissue, and very rarely inflammation of the 
vein or formation of blood clots). Therefore blood withdrawal will only be conducted by qualified 
medical personnel. 

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3.2 
Stress/risks due to the investigational medicinal product (IMP) 
General safety and tolerability of MP1032 has been assessed in one phase 1 first-in-man 
clinical trial. In the single ascending doses part of this trial, twelve volunteers were administered 
50 to 600 mg MP1032. One mild ADR (“headache”) was reported once after treatment with 50 
mg MP1032 in one volunteer. No ADRs were reported in the multiple ascending doses part 
where volunteers received 2×100 mg per day and 2×300 mg per day at 12-hour intervals for 
seven consecutive days.  
In a previous IIa trial following TEAEs were observed: In summary the number of patients with 
TEAEs was 14 (60.87%, 27 TEAEs) in the MP1032 group and 15 (65.22%, 32 TEAEs) in the 
placebo group. The most commonly reported TEAEs were in the SOC categories of infections 
and infestations (5 patients [21.74%] in the MP1032 group and 8 patients [34.78%] in the 
placebo group) and nervous system disorders (7 patients [30.43%] in the MP1032 group and 3 
patients [13.04%] in the placebo group). No clinically important differences were seen between 
the two treatment groups with regard to the number and overall pattern of patients reporting 
TEAEs by System Organ Class (SOC). 
A positive phototoxic signal detected in non-clinical studies could be indicative of a likely clinical 
phototoxic risk of MP1032, although the risk for the patients seems to be unlikely and no 
associated TEAEs were seen in the previous clinical trials. Nevertheless, psoriasis patients 
participating in this trial should be advised to minimize sun exposure (sun bathing) and strong UV 
exposure (see also inclusion criterion No. 9). Furthermore, the use of sunscreen will be 
recommended when spending an extended period of time outdoors. The latter requirement will 
be valid during the whole 12 weeks of treatment duration plus the 4 weeks of follow up period. 
Women of childbearing potential (WCBP) must agree to use a highly effective contraceptive 
method (Pearl-Index < 1%) starting at screening and continuing throughout the clinical trial period 
and for 28 days after final IMP administration. 
Highly effective forms of birth control (according to International Conference on Harmonization 
[ICH] M3) have low failure rates (i.e. less than 1% per year) when used consistently and correctly, 
and include the following: 
 
The male partner of a female patient has undergone effective surgical sterilization. 
 
A female patient can use an established oral contraceptive, injected or implanted 
hormonal methods of contraception or an established intrauterine device or 
intrauterine system. 

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True sexual abstinence as a form of birth control will be allowed in the trial when this is in 
accordance with a patient’s preferred and common lifestyle. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of 
a trial, and withdrawal are not acceptable methods of contraception. Patients who use abstinence 
as a form of birth control must agree to abstain from heterosexual intercourse from the month 
prior to screening until 28 days after the last dose of IMP (or longer if required by local 
regulations). Study personnel must confirm the continued use of abstinence is still in accordance 
with the patient’s lifestyle at regular intervals during the trial. 
Post-menopausal is defined as 12 months of spontaneous amenorrhea. Females who have 
been sterilized, or had a hysterectomy, may be included. 
A sterile woman is defined by either of the following medical interventions performed before 
intake of IMP 
 
Tubal ligation, or 
 
Bilateral oophorectomy, or 
 
Total hysterectomy. 
If documented, women with one of these conditions are not required to use additional 
contraception. 
 
Male patients who are sexually active with a female partner and are not surgically sterile 
(vasectomy performed at least six months prior to treatment) must agree to inform their female 
sexual partner about his trial participation and to use an acceptable form of birth control as 
described in the informed consent form. Prior to trial enrollment, patients must be advised of the 
importance of avoiding pregnancy during trial participation and the potential risk factors for an 
unintentional pregnancy. The patient must sign an informed consent form documenting this 
discussion. 
Against these minimal risks stands the benefit of information on the efficacy and safety of a 
promising new substance which is intended to be used in the oral administration in patients with 
psoriasis vulgaris.  
Taking into account these risks and benefits, the performance of the trial can be considered 
ethically sound since the expected benefits of the IMPs appear greater at present than the risks 
for the patients. The clinical trial protocol will be submitted to the responsible ethics committee(s) 
for approval. 

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5. 
Investigational plan 
5.1 
Overall trial design and plan - description 
This trial is a randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy 
and safety of two oral doses of MP1032 (150 mg bid and 300 mg bid) in adult patients with 
moderate-to-severe chronic plaque psoriasis. 
The trial design consists of a 28-day screening period, a 12-week treatment period, and 
subsequently a 28-day follow-up period. Each patient will have 6 visits and unscheduled visits as 
needed. 
Approximately 150 patients (2 × 50 patients MP1032 and 50 patients placebo) who meet the entry 
criteria will be randomized on Day 1 to receive either 150 mg MP1032, 300 mg MP1032 or 
placebo orally twice daily for 12 weeks. The administration of IMP will stop after end of study (in 
max. 13 weeks). Recruitment will be competitive between the sites but enrollment will be limited 
to 12 patients per site. A recruitment of more than 12 patients may be allowed after sponsor 
approval.  
Safety parameter will be monitored from the signing of the informed consent form (ICF) until the 
last follow-up visit. 
Efficacy and safety will be assessed as outlined in the trial flow chart. 
5.2 
Discussion of trial design, including the choice of control groups 
Pre-clinical toxicology studies, a Phase I single plus multiple ascending dose trial, as well as an 
exploratory Phase IIa pilot trial of oral MP1032 have indicated a higher degree of safety and 
tolerability of the IMP compared to all currently used systemic psoriasis treatments. Moreover, a 
first assessment of oral MP1032’s clinical efficacy in moderate-to-severe psoriasis in the 
preceding Phase IIa trial has shown clinically meaningful response in patients who entered the 
trial with a PASI score of 10-20 during six-week treatment period. 
In several animal models of chronic, immune-mediated inflammatory diseases, MP1032 has been 
shown to have a pronounced anti-inflammatory effect. 
The primary objective - to evaluate clinical efficacy and safety of MP1032 in patients with psoriasis 
during the 12-week treatment period and a 4-week follow up - will provide an opportunity to 
perform oral MP1032’s clinical efficacy in moderate-to-severe psoriasis when taken for twice as 
long as done in Phase IIa.  

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On the basis of pre-clinical, Phase I and Phase IIa data, the current trial was also designed to 
assess the safety and tolerability of oral MP1032 over a period of 12 weeks, trying to reproduce 
the excellent tolerability and safety profile that was seen in Phase I and Phase IIa (up to 7 days 
and 6 weeks, respectively), over a longer period of time.  
The extension of treatment to 12 weeks and a 4-week follow-up observation period will give the 
opportunity to obtain even more meaningful safety data and more comprehensive data on 
efficacy.  
To evaluate systemic concentrations of MP1032 PK samples will be analyzed in a subgroup. 
The photographic documentation will only be used for visual demonstration of efficacy. No 
assessments will be performed using this data. 
Patients will be randomized to one of three treatment arms (MP1032 600mg, MP1032 300mg or 
placebo) in a blinded manner. The treatment allocation will be on a 1:1:1 ratio (50:50:50 patients). 
Recruitment will be competitive between the sites but enrollment per site will be limited to 
12 patients (more than 12 patients needs to be approved by the sponsor).  
5.3 
Selection and discontinuation/withdrawal of patients 
5.3.1 Selection of patients 
The selection of patients is in accordance with the requirements of the national laws as well as 
the recommendations of the currently valid revision of the Helsinki Declaration [4] and the ICH 
GCP guideline [5]. Advertisement (e.g. newspaper, online portal, bus or metro) will be used only 
after positive approval by the responsible EC.  
The trial population will consist of approx. 150 patients (planned 75 Germany and 75 Poland) with 
moderate-to-severe chronic plaque psoriasis. Patients must be able to provide written consent 
and meet all the inclusion criteria and none of the exclusion criteria. 
A gender specific subdivision into groups is not necessary in this clinical trial. Male or female 
patients between 18 years and 70 years are eligible for this clinical trial insofar that they suffer 
from moderate-to-severe-psoriasis. The antipsoriatic efficacy is likewise detectable in men and 
women. 

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5.3.2 Inclusion criteria 
All of the following criteria have to be met for inclusion of a patient in this trial: 
1. Participants legally competent to sign and give informed consent.  
2. Adult male and female patients between 18 years and 70 years with moderate-to-severe 
chronic plaque psoriasis (diagnosed by Investigator): 
a) PASI score ≥10 - ≤20 at baseline  
b) BSA score: > 10% 
c) Stable disease duration of ≥ 6 months at the initiation of IMP. 
d) topical therapy fails to control the disease 
3. Body Mass Index (BMI) between 18.5 and 34.9 kg/m2. 
4. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at 
Screening (Visit 1). In addition, sexually active WCBP must agree to use adequate 
contraception throughout the trial (see Section 3.2 for more details on adequate 
contraception): 
a) A method with less than 1% failure rate OR 
b) Abstinence 
5. Post-menopausal women with spontaneous amenorrhea for at least 12 months and 
women on hormonal replacement therapy (HRT). The use of hormonal replacement 
therapy (HRT) during the trial is permitted, however for these patients an appropriate 
contraception method according to Inclusion Criterion 4 must be ensured. Sterilized 
women may be included (see Section 3.2 for more details on sterile definition) 
6. Male patients who are sexually active with a female partner and are not surgically sterile 
(vasectomy performed at least six months prior to treatment) must agree to inform their 
female sexual partner to use an acceptable form of birth control as described in the 
informed consent form. For females, an acceptable method (Pearl Index < 1%) would be 
to use implants, injectable, combined oral contraceptives, some intrauterine devices, or 
be postmenopausal, be surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy) 
7. In good health as judged by the investigator, based on medical history, physical 
examination, serum chemistry, hematology and urinalysis 
8. Patients must meet the following clinical laboratory criteria: 

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 
White blood cell count ≥3.5 × 109/L 
 
Platelet count ≥100 × 109/L 
 
Serum creatinine ≤1.5 × upper limit of normal (ULN); estimated glomerular 
filtration rate >60 mL/min 
 
Total bilirubin ≤1.5 × ULN 
 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5 × ULN 
 
Hemoglobin ≥ lower limit of normal as per central laboratory reference ranges for 
women and men accordingly 
 
No coagulopathy (International Normalized Ratio [INR] <1.5) 
9. Patients agree to minimize normal sun exposure during the course of the trial 
10. Patients are considered reliable and capable of adhering to the protocol (e.g. able to 
understand the patient information and complete diaries), visit schedule, or medication 
intake according to the judgment of the Investigator. 
5.3.3 Exclusion criteria 
Patients are to be excluded from the trial, when one or more of the following conditions are met: 
1. Patients with non-plaque form of psoriasis (erythrodermic, guttate, pustular form of 
psoriasis). Associated psoriasis arthritis is allowed provided no other in-/exclusion criteria 
are influenced, no forbidden concomitant therapy is required for the well-being of the 
patient and there is no impact on trial objectives as determined by the Investigator. 
2. Treatment with concomitant medication that may affect and provoke or aggravate 
psoriasis, e.g. antimalarial drugs, beta-blockers or ACE inhibitors unless on a stable dose 
for 3 months before IMP intake. 
3. Evidence of skin conditions at the time of Screening Visit other than psoriasis that would 
interfere with evaluations of the effect of the IMP on psoriasis. 
4. Patients with any serious medical condition, laboratory abnormality, or psychiatric illness 
that would prevent the patient from signing the ICF, as assessed by the investigator. 
5. Pregnant or lactating women or women planning to become pregnant during the trial 
and / or within 28 days following the last dose of IMP. 

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5.3.4 Restrictions during the clinical trial 
A positive phototoxic signal detected in non-clinical studies could be indicative of a likely clinical 
phototoxic risk of MP1032, although the risk for the patients seems to be unlikely. Nevertheless, 
psoriasis patients participating in this trial should be advised to avoid strong sun exposure (sun 
bathing) and strong UV exposure (see inclusion criterion no. 9). Furthermore, the use of 
sunscreen will be recommended when spending an extended period of time outdoors. During the 
trial patients should adhere to their standard skin care regimen and may use their standard 
emollients/moisturizers as symptoms require but may not use treatments as precluded by the 
exclusion criteria. The latter requirement will be valid during the whole 12 weeks of trial duration 
plus the 4 weeks of follow up period. 
5.3.5 Removal of patients from therapy or assessment 
5.3.5.1 
Criteria for discontinuing the whole clinical trial 
Premature termination of a clinical trial may occur upon decision of the Sponsor, upon decision 
of the Investigator, by request of an authority, or because of withdrawal of positive vote by the 
responsible IEC. If the Investigator, the Sponsor, or the Medical Monitor becomes aware of 
conditions or events that suggest a possible hazard to patients, if the trial continues, the trial may 
be terminated after appropriate consultation between the relevant parties. The trial may also be 
terminated early at the Sponsor’s discretion in the absence of such a finding.  
Conditions that may warrant termination of the trial as a whole include, but are not limited to:  
 
Concerns for safety that arise within this trial or in any other trial with the IMP;  
 
The discovery of an unexpected, significant, or unacceptable risk to the patients enrolled 
in the trial;  
 
Failure to enroll patients at an acceptable rate;  
 
Ethical issues;  
 
Severe non-compliance;  
 
A decision on the part of the Sponsor to suspend or discontinue development of the 
drug.  
5.3.5.2 
Criteria for discontinuing in the case of individual patients 
Patients may withdraw from the entire trial including follow-up at any time without penalty and for 
any reason without prejudice to his or her future medical care. 
The following criteria must lead to discontinuation from the clinical trial in individual patients: 
 
Patient withdraws informed consent 

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 
Pregnancy (see section 7.4) 
 
Severe protocol violations that result in a significant risk to the patient’s safety 
 
Emergence of the following AEs including: 
a) Patient reports symptoms which are considered unacceptable by the patient or the 
Investigator or if any serious AE occurs that is judged as at least possibly related to 
the IMP by the Investigator 
b) Abnormal laboratory value(s) confirmed by repeat measurements: 
 
Elevated liver transaminases (AST/ALT) ≥3 × ULN AND elevated bilirubin 
total bilirubin ≥ 2 × ULN 
 
Elevated serum creatinine ≥2 × ULN 
The following criteria may lead to discontinuation from the clinical trial in individual patients: 
 
Use of prohibited concomitant medication as defined in section 5.4.5. 
 
In all cases, the reason(s) for withdrawal, and the primary reason, must be recorded on the 
electronic data capture (EDC) system / electronic case report form (eCRF). If a patient is 
prematurely withdrawn from the IMP for any reason, the Investigator must make every effort to 
perform the evaluations described for the End of Treatment and Follow-up Visits. The Investigator 
should contact the Medical Monitor, whenever possible, to approve withdrawal of patients in 
advance. 
If a patient withdraws consent and still agrees to undergo a final examination, it will be 
documented on the eCRF and the patient record.  
A patient may also be withdrawn from the IMP by the Sponsor, Regulatory Authorities, or 
Independent Ethics Committees (IECs) / Institutional Review Boards (IRBs). 
Patients who are withdrawn from the trial will be not replaced. 
Protocol violation, failure to comply with the trial stipulations/poor compliance may lead to 
discontinuation from the clinical trial in individual patients. 
5.3.6 Definition of end of trial 
The end of the trial is defined as the last visit of the last patient completing the trial (including 
follow-up visits). 

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5.4 
Treatments 
The IMP will be packed in kits, 1 kit per patient per week. One kit contains 14 blisters and one 
blister contains six, 50 mg, hard gelatin capsules of MP1032 and/or placebo (described below). 
IMP will be packaged and labelled by 
 according to all local legal 
requirements. IMP will be labelled in accordance with applicable regulatory requirements. 
All IMP supplies must be stored at room temperature (15 - 25°C) and protected from light, in 
accordance with the manufacturer’s instructions. Until dispensed to the patients, the IMP will be 
stored in a securely locked area, accessible to authorized personnel only. 
5.4.1 Treatments to be administered (manner and dose selection) 
Once patients have met the trial entry criteria, completed the screening procedures and run-in 
period, and completed the pre-dose procedures and assessments, they will be randomly assigned 
as described in Section 5.4.3 above to one of the three treatment groups described below. They 
will receive total daily doses of 300 mg or 600 mg MP1032 (IMP) or placebo (IMP placebo) as 
follows (1:1:1): 
 
Treatment A: 3 × 50 mg (150 mg) MP1032 plus 3 × placebo hard gelatin capsules 
(per dosage) twice daily for 84 days 
 
 
Treatment B: 6 × 50 mg (300 mg) MP1032 hard gelatin capsules (per dosage) twice 
daily for 84 days 
 
 
Treatment C: 6 × placebo hard gelatin capsules (per dosage) twice daily for 84 days. 
All administrations will take place with at least 8 hours between the dosings. 
CCI

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5.4.2 Identity of investigational medicinal products 
Details of the IMPs are given in the table 3. 
Table 3:Identity of investigational medicinal products: 
Generic name/brand 
name/INN 
Verum 
Placebo 
Formulation  
Hard gelatin capsules, size 3  
The mixture (995 parts mannitol and 5 parts colloidal anhydrous silica) is 
well 
known 
and 
described 
in 
compendia 
(German: 
Neues 
Rezepturformularium, Monographie Nr. S. p. 38.). At least 25% of the mass 
of the contents are active ingredient. Placebo capsules constituted only of 
the excipients described above. 
Active ingredient 
MP1032 
5-Amino-1,4-dioxo-1,2,3,4-
tetrahydrophthalazine-3-id, sodium 
salt 
n.a. 
Amount per unit 
containing 50 mg MP1032 for oral 
administration 
n.a. 
Primary packaging 
Blister 
Blister 
Storage 
room temperature (15 – 25 °C) 
room temperature (15 – 25 °C) 
Manufacturers 
 
 
 
 
 
 
 
 
All IMPs will be labeled according to the requirements of local law and legislation. A copy of the 
labels will be filed in the trial master file (TMF). 
All IMPs used during the trial will be stored at the trial center in accordance with instructions given, 
and will be inaccessible to unauthorized personnel.  
Missing a treatment 
If the patient misses a dose, and remembers the dose within 6 hours of scheduled dosing, he/she 
may take it. If it has been more than 6 hours since the planned dose time, the patient should skip 
the dose. All missing doses should be documented by the patient in the diary. However, all 
administrations will take place with at least 8 hours between the dosings. 
Overdose 
The risk of overdosing in general in this trial is considered to be low due to the maximum dose 
that each patient can receive via six capsules being 150 mg, 300 mg MP1032 or Placebo. 
Nevertheless, unintentional administration of any dose that deviates from the scheduled regimen 
will be documented and reported by site staff via eCRF. In case of overdose symptomatic 
CCI
CCI

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treatment should be provided as indicated and a safety blood analysis should be performed. The 
Sponsor should be informed immediately.  
5.4.3 Assignment of treatments and randomization 
Patient Identification 
Upon signature of informed consent (screening period) each patient receives a 5-digit patient 
identification number, which is composed of: 
Digits 1 and 2: 
trial center (01, 02, 03, etc.) 01 – 10 for German sites and 11 – 20 for 
Polish sites 
 
Digits 3, 4 and 5: 
individual screening number within the center (consecutively in the order 
of screening within the center: 001, 002, etc.)  
 
Treatment Assignment 
 
Patients will be randomized on a 1:1:1 basis to one of three treatment groups: 
 
 
MP1032 300 mg bid 
 
MP1032 150 mg bid 
 
Placebo bid 
 
The trial will use a block randomization scheme. Enrollment will be performed competitively 
between all 14 centers (Germany and Poland) until approximately 150 patients are enrolled in the 
trial in order to have 120 evaluable patients. 
Patients who are eligible for enrollment into the trial will be randomized at Visit 2/Day 1 and will 
be assigned the lowest random number available at the site. Patient kits will be dispensed 
according to the kit number assigned by the IWRS. The kit numbers will be assigned to the 
treatment kits by a simple randomization.  
The treatment group designation will remain blinded until the final database is locked. 
The random list, assigning the randomization number to the treatment groups, and the kit number 
list, assigning the kit number to the treatment groups will be generated by psy consult scientific 
services.  
5.4.4 Blinding and Breaking the Blind 
 
The trial will be performed in a double-blind manner. All IMPs will be supplied in identical form 
and will be similar in color, smell, taste, and appearance.  
The IMPs will be blinded by 
.  
CCI

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The trial blind should not be broken except in case of a medical emergency (where knowledge of 
the IMP received would affect the treatment of the emergency) or regulatory requirement (e.g. for 
SUSAR [in Germany]).  
If the blind is broken via IWRS, the date, time, person who broke the blind and the reason must 
be recorded in the patient’s eCRF, and any associated AE report.  
The treatment code will only be broken after all the clinical database is locked. 
5.4.5 Prior and concomitant therapy 
Any medication the patient takes other than the IMP, including herbal and other non-traditional 
remedies, is considered a concomitant medication. All concomitant medications taken in the 6 
weeks before the first dose must be recorded in the eCRF. The following information must be 
recorded in the eCRF for each concomitant medication: brand name, route of administration, start 
date, stop date, dosage, and indication. Any changes in the dosage or regimen of a concomitant 
medication must be recorded in the eCRF.  
At Screening, patients will be asked which psoriatic treatment they have previously taken (last 6 
weeks) and which other concomitant medications they have taken in the last 6 weeks. At each 
subsequent trial visit, patients will be asked which concomitant medications they are currently 
taking and have taken since the previous site visit. 
For a detailed list of forbidden medication see exclusion criterion 14. 
Medication allowed during the course of the trial: 
 
Topical moisturizers or emollients, UVA/UVB sunscreens, shampoos for scalp psoriasis 
(without tar), as needed.  
 
Contraceptives (see section 3.2) 
 
Any concomitant medication to treat stable diseases (such as well-controlled 
hypertension, hyperlipidemia, etc.) 
Prohibited medication: 
 
All treatment as specified in exclusion criteria. 
Concomitant medications should be kept to a minimum during the clinical trial. However, if these 
are considered necessary for the patient's welfare and are unlikely to interfere with the clinical 
trial objectives, they may be allowed at the discretion of the investigator. For a detailed list of 
forbidden medication see exclusion criterion 14. 

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5.4.6 Treatment compliance 
All treatment administrations (except first for the PK subgroup and last treatment for all patients) 
will be taken by the patients at home. All treatment administrations will be documented in a diary. 
All missing treatment administrations documented in the diary will be counted and documented 
in the eCRF.  
All dispensed kits and blisters (used and unused) will be collected at each visit and capsules will 
be counted at each visit during the treatment period. The results will be documented in the eCRF.  
In case of inadequate usage the patient will be instructed again on application use. 
5.5 
Efficacy and safety variable(s) 
5.5.1 Procedures 
Screening period  
Day -28 to -3 (visit 1)  
Within the 28 days prior to the first IMP administration the volunteer will come to the trial centers 
for the initial screening (including documentation of demographic data). Screening assessments 
will be performed after the volunteer has agreed to participate and has signed and dated the 
informed consent form.  
At screening a serum pregnancy test will be carried out in all female patients. 
The following examinations will be performed: 
 Obtain written informed consent 
 Documentation of relevant medical and relevant surgical history (last 5 years) 
 Documentation of demographic data 
 Documentation of Smoking history/ alcohol consumption 
 Documentation of relevant previous medication (last 6 weeks) 
 Serum pregnancy test and urinalysis (see section 5.5.2) 
 Start check in-/exclusion criteria (see section 5.3.2 and 5.3.3) 
 Physical examination (see section 5.5.5) 
 Height, body weight and BMI 
 Record vital signs (see section 5.5.3) 
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2)  
 BSA (see section 5.5.1.3) 

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 Collection of samples for determination of laboratory parameters (serology, hematological 
status, clinical chemistry, see section 5.5.2). 
Note: Adverse events before start of treatment (i.e. occurring after signature on consent form). 
Patients who have abnormal test results during the screening period may be re-screened if the 
Medical Monitor agrees. 
Experimental phase 
Trial Day 1 (baseline, week 1, visit 2) 
 Re-check of in-/exclusion criteria (see section 5.3.2) 
 Randomization 
 Physical examination (see section 5.5.5) 
 Record vital signs (see section 5.5.3) 
 Urine pregnancy test and urinalysis (see section 5.5.2) 
 Record concomitant medications 
 Record adverse events occurring from the time of informed consent signature 
 Localization of photographic documentation test field only for a subgroup (see section 5.5.1.4) 
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, see section 5.5.2)  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 Dispensing diary  
 Start of PK samples only for a subgroup (see section 5.5.1.5) 
 Dispensing IMP  
 Administration of IMP at site (PK subgroup only)  
 
Trial Day 28 (week 4, visit 3) and Day 56 (week 8, visit 4)  
 Check concomitant therapy and adverse events 
 Record vital signs 
 Drug return / accountability and re-dispensation of unused kits/blister 
 Diary collected and checked  
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Urinalysis (see section 5.5.2) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, urinalysis, see section 5.5.2)  
 PASI (see section 5.5.1.1) 

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 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 Dispensing of IMP and diary 
 
Trial Day 84 (week 12, visit 5) (EoT) 
 Check concomitant therapy and adverse events 
 Physical examination (see section 5.5.5) 
 Record vital signs (see section 5.5.3) 
 Urine pregnancy test and urinalysis (see section 5.5.2) 
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, see section 5.5.2)  
 PK samples only for a subgroup (see section 5.5.1.5) 
 Last IMP administration at site for all patients 
 Drug return / accountability  
 Diary collected and checked  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 
Trial Day 112 (week 16, visit 6, Follow-up) (End of Study, EoS) 
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Check concomitant therapy and adverse events 
 Physical examination (see section 5.5.5) 
 Record vital signs (see section 5.5.3) 
 Urinalysis(see section 5.5.2) 
 Collection of samples for determination of laboratory parameters (hematological status, 
 clinical chemistry, see section 5.5.2)  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 
The patients must be present at site for approximately 60 minutes on Screening and Day 1, 45 
minutes on Day 28 and 56, 60 minutes on Day 84 and 45 minutes on Day 112. 
The above mentioned time will be extended for 15 minutes for patients with photographic 
documentation on each visit.  

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The above mentioned time will be extended on Day 1 and Day 84 for 120 minutes for patients 
with PK sampling.  
 
Early Termination Visit 
Patients who discontinue early from the trial should, if possible, have an Early Termination Visit. 
This visit should take place as soon as possible after the patient stops taking IMP. The 
observations and procedures scheduled for Visit 5 (End of Treatment) should be performed at the 
Early Termination Visit. 
A schedule of trial procedures is provided in appendix A to this trial protocol. 
Unscheduled visit 
The patient may return to the clinic at the discretion of the investigator.  
At this visit, the investigator or designee will:  
• Query the patient about any changes in health status or concomitant medications and therapies 
since the previous visit, and document the findings respectively (AE/concomitant medications)  
• Perform assessments which are relevant to the reason for the unscheduled visit (e.g. 
Photographic documentation, Lab analysis, PASI, PGA, BSA, etc.) 
• Confirm the next visit 
5.5.1.1 
Psoriasis Area Severity Index (PASI)  
The PASI is the most commonly used and validated assessment for grading the severity of 
psoriasis in clinical studies [2]. The PASI is a physician’s assessment of psoriasis that is a 
therapeutic standard in clinical studies for this disease (appendix B). The PASI quantifies the 
severity and extent of the disease and weighs these with the body surface area involvement. It 
involves the assessment of erythema, infiltration, desquamation, and body surface area 
involvement over 4 body regions: head, trunk, upper and lower extremities.  
The Investigator assesses the redness, thickness, and scaliness of lesions on a 5-point scale 
(from 0 = none, through 4 = severe). The percentage of skin involved is scored and transferred to 
a grade (graded 0 to 6; 0 = 0% involved area, 6 = 90%-100% involved area). In addition, the 
percentage of involved body surface area is estimated across 4 body areas, head (10%), upper 
extremities (20%), trunk (30%), and lower extremities (40%). The sum of all 3 severity parameters 
is then calculated for each of the 4 sections of skin, multiplied by the area score for that area, and 
multiplied by the weight of the respective section to give a PASI score, which ranges from 0 to 
72, with a higher score indicating increased disease severity. The PASI will be completed by the 

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Investigator or designee at the time points prior to and following IMP administration as defined in 
the trial schedule. See appendix B for details of calculation. 
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. Initials of the assessor will be documented in the eCRF. 
5.5.1.2 
Physician`s Global Assessment (PGA)  
The PGA provides an overall evaluation of the severity of the disease [6]. The PGA is a 7-point 
physician’s assessment of psoriasis that is a therapeutic standard in clinical studies for this 
disease.  
The Investigator or designee will complete a PGA form to evaluate the disease severity at a single 
time point. Scoring is on a 7-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = mild to 
moderate; 4 = moderate; 5 = moderate to severe, and 6 = severe. The PGA will be completed by 
the Investigator (or designee) at the time points specified.  
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. Initials of the assessor will be documented in the eCRF. 
5.5.1.3 
 Assessment of body surface area (BSA)  
The total surface area of the body affected with psoriasis plaques will be determined by the 
Investigator at V2 (Wk0-D1), V3 (Wk4-D28), V4 (Wk8-D56), V5 (Wk12-D84), and V6 (Wk16-
D112). Calculation should include psoriasis on the palms of the hands and soles of the feet as 
well as on the face and scalp. The investigator will calculate the approximate BSA by assuming 
that 1% BSA is approximately equal to the surface area of one outstretched hand (with fingers) 
of the patient [2].  
The assessment of BSA by the Investigator serves to describe the change in % BSA affected by 
psoriasis after 12 weeks of treatment.  
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. 
5.5.1.4 
Photographic documentation 
At all visits photographic documentation of one affected area (from trunk, arms or legs) will be 
performed in a patient subgroup at two selected trial sites (one site in Germany and one in Poland; 
approximately 30 patients in total). The target plaque for the photographic documentation will be 
defined before first treatment on Day 1 and should mirror the actual individual psoriasis grade of 

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5.5.1.6 
Diary 
The diaries will include instructions on the use of the IMP. Patients will be instructed to complete 
the diary after intake of each IMP dose. Date/time of intake of IMP will be recorded twice daily.  
At each visit at the site, the number of dose recorded on the diary will be reviewed and transcribed 
to the eCRF. Diary cards will be retained by trial sites as part of the source documentation and 
new diary cards will be dispensed. 
At subsequent visits, trial personnel will review, collect and dispense a new diary and determine 
whether the patient requires counseling for dosage compliance. In addition, each patient will be 
reminded to return completed diary at the next visit. 
5.5.2 Measurement of safety parameters 
Relevant medical history of the past five years and adverse events will be recorded.  
The following laboratory parameters will be collected at every visit (except serology): 
 
Table 4: Laboratory Parameter per visit: 
Parameter 
Screening 
Day 1 
Day 28 / 
56 
Day 84 
(EoT) 
Day 112 
(FU) 
Serology 
Hepatitis A IgG-antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis A IgM-antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis B core antibody-test  
X 
-- 
-- 
-- 
-- 
Hepatitis B surface antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis B surface antigen-test 
X 
-- 
-- 
-- 
-- 
Hepatitis C virus antibody-test 
X 
-- 
-- 
-- 
-- 
HIV-1 antibody-test 
X 
-- 
-- 
-- 
-- 
HIV-2 antibody-test 
X 
-- 
-- 
-- 
-- 
Hematology 
RBC 
X 
X 
X 
X 
X 
WBC* including differential 
X 
X 
X 
X 
X 
Hemoglobin 
X 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
X 
MCH 
X 
X 
X 
X 
X 
MCV 
X 
X 
X 
X 
X 
MCHC 
X 
X 
X 
X 
X 
Platelets 
X 
X 
X 
X 
X 
Clinical Chemistry 
AST (GOT) 
X 
X 
X 
X 
X 

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Parameter 
Screening 
Day 1 
Day 28 / 
56 
Day 84 
(EoT) 
Day 112 
(FU) 
ALT (GPT) 
X 
X 
X 
X 
X 
GT 
X 
X 
X 
X 
X 
AP 
X 
X 
X 
X 
X 
Creatinine 
X 
X 
X 
X 
X 
Total bilirubin 
X 
X 
X 
X 
X 
CRP 
X 
X 
X 
X 
X 
hCG serum 
X 
-- 
-- 
-- 
-- 
Urine 
Urine dip stick test** 
X 
X 
X 
X 
X 
* including lymphocyte, neutrophils count, and eosinophils 
** leukocytes, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood/hemoglobin 
 
Hematological status, serology and clinical chemical parameters will be determined by LKF, Lise-
Meitner-Str. 25 – 29, 24223 Schwentinental, Germany. Urinalyses will be performed at the sites 
using a dipstick test (Medi-Test®, Combi 10L, Macherey-Nagel, Dueren, Germany). 
Approximately 19.2 ml of blood will be withdrawn at each visit with laboratory analysis (in total 
approximately 116 mL per patient). For the PK subgroup additional 24.5 mL will be withdrawn on 
day 1 and day 84 (in total 49 mL per patient). 
Spontaneously noted complaints will be recorded with duration, intensity and probability of a 
correlation with the IMP (see section 7.3., evaluation of adverse events). 
5.5.3 Vital signs 
Blood pressure and pulse rate will be measured at all visits after at least 5 minutes in a seated 
position. The following ranges for vital signs are given in table 5.  
Table 5: Vital signs ranges 
Variable 
Units 
Acceptable limit 
Systolic blood pressure 
mm Hg 
80 - 150 
Diastolic blood pressure 
mm Hg 
60 - 95 
Heart rate 
beats/min 
50 – 100 
Values outside 160 mm Hg / 95 mm Hg will not be randomized. 
5.5.4 Smoking and alcohol consumption  
Information on smoking and alcohol consumption will be documented at screening. 

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5.5.5 Physical examination 
The physical examination comprises a routine medical examination including gross neurological 
assessments. The following body systems will be examined: basic status of the main organ 
systems (ENT, heart, lungs, abdomen, neurological status) as well as physical examination of the 
skin. 
5.5.6 Appropriateness of assessments 
PASI, PGA, BSA are widely used, non-invasive methods for examining overall psoriasis severity 
and coverage. 
These methods are described in the EMA guideline [2] for evaluation of product efficacy. 
Assessments should be conducted by investigators who are experienced and have been trained 
on the use of these evaluation tools. If possible, the same investigator should complete the 
evaluations for a given patient throughout the trial. 
5.5.7 Primary efficacy/tolerability variable(s) 
Primary variable: 
The primary efficacy variables are: 
1. 75% improvement (response) in their PASI score (PASI 75) and  
2. Improvement (1 or more points on a 7 point scale) in their PGA score 
The secondary efficacy variables are: 
1. 50% improvement (response) in their PASI score (PASI 50)  
2. Mean PASI score and change to baseline  
3. Time to achieve PASI 50 and PASI 75 
4. Mean score and change from baseline in the PGA 
5. Mean score and change from baseline in the BSA 
6. PK data  
The 
primary 
variables 
are 
choose 
in 
accordance 
to 
the 
EMA 
guideline 
http://www.ema.europa.eu/docs/en GB/document library/Scientific guideline/2009/09/WC5000
03329.pdf (4)  

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6. 
Data analysis and statistics 
The statistical evaluation will be performed at bioskin using the software program SAS® (Statistical 
Analysis System, SAS, Cary, NC), Version 9.3 or higher.  
A formal statistical analysis plan (SAP), providing a complete description of the methodology of 
the planned statistical analyses, will be written, finalized, and signed prior to breaking the trial 
blind. Any changes in the statistical methods described in this protocol that occur prior to database 
lock will be documented in the SAP and will not require a protocol amendment.  
6.1 
Generation of data base 
In general, data from the source documents will be captured in an eCRF by a software package 
that can be customized for remote data entry procedure and that maintains an electronic audit 
trail. The eCRFs will be developed in the EDC system in accordance with bioskin SOPs under 
supervision and in agreement with the sponsor. The database structure will be validated.  
Only authorized site personnel will be able to enter/modify/correct data to the eCRF. The 
investigator/coordinator or designee must enter the information required by the protocol as soon 
as possible after the visit into the eCRF.  
The data will be checked for consistency. Queries for discrepant data may be generated 
automatically by the system upon entry or generated manually by the monitor or the trial data 
manager. All queries, whether generated by the system or by a user, will be in an electronic 
format. Once all the queries are closed and data have been verified by the CRA, the eCRF will 
be signed (eSignature) by the investigator and the database will be locked.  
All data management procedures will be detailed in a separate, specifically identified file that 
collectively will be referenced as the (DMP). 
Adverse events and medical history will be coded with Medical Dictionary for Regulatory Activities 
(MedDRA) mapping system, previous and concomitant therapy will be coded according to WHO-
DD. 
Patient data in PDF files generated from the eCRF will be provided to the site at the end of the 
trial. 
6.2 
Analysis sets and type of analysis 
The safety-evaluation-set (SES) will include all patients who received any trial medication at least 
once; all safety analyses will be based on the SES. 

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The full-analysis-set (FAS) will include all randomized patient who received at least one dose of 
IMP, and had at least one post-baseline assessment. The intention-to-treat (ITT) analysis will be 
based on the FAS. 
The valid-cases-set (VCS) will include all patient from the FAS, without any protocol violation 
interfering with the trial aims and with sufficient exposure to IMP. The per-protocol (PP) analysis 
will be based on the VCS.  
6.3 
Hypotheses 
Since this is an exploratory trial no formal hypotheses are postulated. The data will be evaluated 
descriptively. 
6.4 
Rationale for the sample size 
It is planned to recruit approximately 150 patients for this clinical trial in Germany and Poland 
(each country approximately 75 patients) to achieve 120 evaluable patients.  
No formal sample size calculations were performed for this explorative trial. A sample size of 40 
in each group is adequate to detect a difference in rates of at least 0,274, with 80% power, using 
a two group ﬡ2 test with a 0,100 two-sided significance level. 
6.5 
Statistical methods 
Statistical analyses will be performed using two-sided tests, without adjustment for multiplicity. All 
p-values will be interpreted descriptively.  
Data will be summarized by treatment group (and by visit when applicable), with respect to 
demographic and baseline characteristics, efficacy variables, and safety variables. 
Summary statistics will include the mean, number of non-missing cases (n), standard deviation, 
median, minimum, and maximum values for continuous variables, and frequencies and 
percentages for categorical variables. 
Categorical efficacy variables will be analyzed using the Cochran-Mantel-Haenszel (CMH) test 
with stratification by (pooled) analysis center and the Fisher’s exact test in case of analyses 
without stratification (mainly for safety assessment). 
Selected scores will be analyzed using an analysis of covariance (ANCOVA) model, with 
treatment group and (pooled) analysis center as factors and baseline outcome as covariate.  

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Time to event data will be analyzed using the Kaplan-Meier method, and treatment group 
differences will be tested by the log-rank test.  
Unless otherwise specified, baseline is defined as the latest non-missing observation prior to first 
treatment with IMP. 
Details of the model and the analyses will be specified in the SAP.  
6.5.1. Efficacy analyses 
Primary efficacy endpoints 
The comparisons of the treatment groups MP1032 300 mg bid and MP1032 150 mg bid, each vs. 
the placebo treatment, with respect to each, the PASI 75 rate and PGA improvement rate, at 
Week 12 (Day 84) will be evaluated by the CMH test stratified by (pooled) analysis center. The 
common odds-ratio with 95% confidence interval will be provided. The homogeneity of the 
individual odds-ratios will be assessed by the Breslow-Day test.  
Secondary efficacy endpoints 
Secondary efficacy endpoints will be evaluated descriptively. The methodology outlined in section 
6.5 will be applied for pairwise treatment comparisons vs. placebo.  
Responder rates will be evaluated as the primary efficacy endpoint.  
The change in the PASI score from baseline to each post baseline visit, respectively, will be 
evaluated using an analysis of covariance (ANCOVA) model, with treatment group and (pooled) 
analysis center as factors and baseline outcome as covariate.  
The time to achievement of PASI 50 and PASI 75, respectively, will be evaluated using the 
Kaplan-Meier method. Pairwise treatment group differences will be tested by the log-rank test. 
Descriptive summaries will be provided for each parameter by treatment group and by visit, if 
applicable. Percentages will be provided based on the number of non-missing cases, if not 
otherwise stated.  
6.5.2. Safety analyses 
All AEs reported during the trial will be listed, documenting course, severity, investigator 
assessment of the relationship to the IMPs, and outcome. AEs will be coded using the MedDRA 
mapping system for preferred terms (PTs) and system organ class (SOC).  

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Treatment-emergent adverse events (TEAEs), i.e. AEs with an onset or worsening on or after the 
time of the first IMP application will be summarized by the number of patients reporting TEAEs, 
primary system organ class (SOC), preferred term (PT), severity, and relationship to IMP.  
Listings of serious adverse events (SAE) and patients who prematurely discontinued treatment 
due to AEs will be given. 
Safety laboratory parameters (hematology, clinical chemistry) and vital signs will be summarized 
descriptively, including changes from baseline. Urinalysis outcomes will be summarized by 
frequency counts. 
6.5.3. Other analyses 
Blood MP1032 concentration-time data will be listed and displayed graphically, including the 
nominal and actual blood sampling time relative to the corresponding IMP administration time. 
Summary statistics of MP1032 levels by nominal sampling time will be provided. 
Statistical analyses will be performed using non-compartmental analysis (NCA) methods, as 
appropriate, providing Cmax, tmax and AUC(0,t). Listings and summary statistics of NCA parameters 
will be provided. 
6.6 
Handling of dropouts and missing data 
For the evaluation of success rates of the primary efficacy variables PASI and PGA missing PGA 
assessments and/or any parts of the PASI assessments will be evaluated as failure to achieve 
improvement. For descriptive analyses of PASI, PGA and BSA the last observation carried 
forward (LOCF) principle will be applied to impute the missing assessments, up to the Day 84 
visit. Follow-up assessments will not be imputed.  
Sensitivity of the primary efficacy analyses will be evaluated applying PP analyses.  
Handling of missing AE data, will be detailed in the SAP.  
6.7 
Identification of source data 
For the following source data should be available: 
 
patients identification incl. age, height and weight 
 
relevant previous and concomitant therapies  
 
up-to-date relevant medical history (last 5 years) 
 
findings at physical examination 
 
pregnancy test results 

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 
date of entry into the trial/visit dates 
 
vital signs 
 
adverse events  
 
laboratory results 
 
photographic documentation (at the selected sites) 
 
assessment scores PASI, PGA and BSA 
 
PK sampling (at the selected sites) 
 
Randomization number 
 
date and time of assessments  
 
IMP return / accountability and administration  
 
Missing treatment (diary) 
7. 
Adverse events 
7.1 
Evaluation of adverse events 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical trial subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
The period of observation for adverse events extends from the time the patient gives informed 
consent until the trial is completed. Adverse events that are still present after the last patient’s 
scheduled visit will be followed up 28 days of receiving the last IMP dose by means of a visit. 
After that time point the need for additional follow-up of ongoing AEs/SAEs will be discussed 
between the investigator and the sponsor, although in the event of discrepancies the investigator’s 
criteria will prevail. Adverse events occurring after the end of the clinical trial must be reported if 
the investigator considers there is a causal relationship with the investigational product. 
The investigator will be responsible for the necessary acute medical treatment of any adverse 
event required during the trial and will ensure that appropriate medical care will be maintained 
thereafter, if necessary. 
All patients experiencing adverse events - whether considered related with the use of the IMP or 
not - will be monitored until symptoms subside and any abnormal laboratory values have returned 
to baseline, or until there is a satisfactory explanation for the changes observed, or until death, in 
which case a full pathologist's report will be supplied, if possible. "Related" means a reasonable 

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possibility that the event may have been caused by the IMP. All findings will be reported on an 
"adverse event"/“serious adverse event“ page in the case report form. 
All adverse events, including intercurrent illnesses, will be reported and documented as described 
below. 
Adverse events are divided into the categories "serious" and "nonserious". This determines the 
procedure which will be used to report/document the adverse event (see below). 
Surgical procedures themselves are not adverse events; they are therapeutic measures for 
conditions that require surgery. The condition for which the surgery is required is an adverse 
event, if it occurs or is detected during the trial period. Planned surgical measures permitted by 
the clinical trial protocol and the condition(s) leading to these measures are not adverse events, 
if the condition(s) was (were) known before the start of treatment with investigational product. In 
the latter case the condition should be reported as medical history.  
7.2 
Definition of serious and nonserious adverse events 
A serious adverse event is any untoward medical occurrence that at any dose: 
• results in death or is life-threatening; 
• results in permanent or significant disability/incapacity; 
• requires inpatient hospitalization* or prolongation of hospitalization; 
• results in a congenital abnormality/birth defect. 
 
Medical and scientific judgment will be exercised in classification of other important medical 
events that may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the patient or may require intervention to prevent one of the other outcomes listed in 
the definition above. These should also usually be considered serious. 
Adverse events which do not fall into these categories are defined as nonserious. 
*Hospitalization solely for the purpose of diagnostic tests, even if related to an adverse event, 
elective hospitalization for an intervention which was already planned before the inclusion of the 
patient in the clinical trial, and admission to a day-care facility may not themselves constitute 
sufficient grounds to be considered as a serious adverse event.  

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7.3 
Reporting/documentation of adverse events 
7.3.1 Reporting of adverse events 
Adverse events either reported by the patient, or observed by the investigator must be recorded 
on the adverse event page of the eCRF and should be described in the following manner: 
The nature of the event will be described in precise, standard medical terminology (i.e. not 
necessarily the exact words used by the patient). If known, a specific diagnosis should be stated 
(e.g., allergic contact dermatitis). 
The intensity of the adverse event will be described in terms of mild, moderate or severe 
according to the investigator’s clinical judgment. 
• 
Mild: The adverse event does not interfere in a significant manner with the patient’s normal 
functioning level, but may be an annoyance.  
• 
Moderate: The adverse event produces some impairment of functioning but is not 
hazardous to health, but is uncomfortable and/or an embarrassment.  
• 
Severe: The adverse event produces significant impairment of functioning or 
incapacitation and is a hazard to the patient.  
The duration of the event will be described by the start date and end date. 
The causal relationship of the event to use of the IMP will be described in terms of: 
Certain: the adverse event 
• occurs in a plausible time relationship to IMP administration, and cannot be explained by 
concurrent disease or other drugs or chemicals, and 
•  follows a clinically plausible response to withdrawal of the IMP, and 
•   is definitive based on recognized pharmacological or other parameter associated with the IMP, 
and 
•   is confirmed by rechallenge procedure, if performed.  
Probable: the adverse event 
•  follows a reasonable temporal sequence from administration of the IMP, and 
•  is unlikely to be attributed to a disease or other drug/s, and 
•  disappears or decreases on withdrawal of the IMP 
 

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Possible: the adverse event 
•  follows a reasonable temporal sequence from administration of the IMP, but 
•  can also be explained by disease or other drugs, and 
•  information on drug withdrawal may be lacking or unclear.  
Unlikely: the adverse event 
•  does not follow a reasonable temporal sequence from administration of the IMP, and 
•  can be reasonably explained by disease or other drug/s, and 
•  does not follow a known pattern of response to the IMP, and 
•  does not reappear or worsen upon re-challenge, if performed.  
Not related: the adverse event 
• The event is either a pre-dose event or is definitely due to causes separate from the 
administration of the IMP, i.e. 
- documented pre-existing condition 
- technical and manual procedural problems 
- concomitant medication 
- patient’s clinical state 
The outcome of the event will be described in terms of: 
•  Recovered/resolved 
•  Recovering/resolving 
•  Recovered/resolved with sequelae 
•  Not recovered/not resolved 
•  Fatal 
•  Unknown 
It will also be recorded if the IMP use is continued, interrupted or discontinued. 
Note: Insofar as possible all serious adverse events should be followed-up to determine the final 
outcome of the event. Details of follow-up should be given (e.g. discontinuation of IMP, if specific 
treatment is required, if hospitalization is required, FU by PharmaLex, FU by Investigator etc.). 

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For the purpose of expedited reporting for the causality assessment (i.e. relationship of the 
adverse event to IMP) the terms “probable” and “possible” describe a relationship to IMP 
treatment, whereas the terms “unlikely” and “not related” classify the event as being not related 
to IMP treatment. 
7.3.2 Reporting of serious adverse events  
The investigator shall report all serious adverse events immediately (within 24 hours after he 
becomes aware of the event) by fax or e-mail to PharmaLex. General information on the patient 
(pseudonymed), the randomization number, and screening identification number event term 
(diagnosis) and measures already taken are to be reported. The immediate report shall be 
followed by detailed, written reports. The investigator is obliged to completely document the 
course of the event and the measures taken, if possible including the original findings and using 
the form for serious adverse events. Additional documentation is carried out on the case report 
forms. 
SAE reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
 
 
For reported deaths of a patient, the investigator shall supply the sponsor and the ethics 
committee with any additional information requested. 
The sponsor/PharmaLex shall ensure that all relevant information about suspected unexpected 
serious adverse reactions (SUSAR) that are fatal or life-threatening is recorded and reported as 
soon as possible to the competent authorities in all the member states concerned, and to the 
ethics committee, and in any case no later than seven days after knowledge by the sponsor of 
such a case, and that relevant follow-up information is subsequently communicated within an 
additional eight days.  
All other SUSARs shall be reported to the competent authorities concerned and to the ethics 
committee concerned as soon as possible but within a maximum of fifteen days of first knowledge 
by the sponsor accordingly.  
PharmaLex shall also inform all investigators.  
CCI, PPD

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7.4 
Pregnancies  
Pregnancies occurring during a patient's participation in a clinical trial, although not 
typically considered an SAE, must be notified to the sponsor within the same timelines as an 
SAE (within 24 hours after being made aware of the pregnancy) on a pregnancy notification form. 
The pregnant trial patient should be withdrawn immediately from the trial. 
Pregnancy reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
 
 
Any pregnancy occurring in the trial should be followed up until outcome. If relevant, the 
development of the newborn has to be monitored for an appropriate time post-delivery. 
8. 
Case report form (CRF), documentation and archiving 
•  The CRFs will be drawn up by bioskin in agreement with the sponsor. 
•  All trial documents, in particular the eCRFs, must be continually filled out. The eCRF is validated  
   system which automatically creates an audit trail for all changes. 
•  The documentation will be kept in such a way, that it is possible to easily reconstruct the course  
   of the trial at a later date (in accordance with the details given in the clinical trial protocol). All  
   documents will be filed in the TMF or the investigator file, respectively. 
•  Following the specific patient information, consent forms will be signed by the patient and the  
   physician responsible for supplying information twice. One will be filed in the investigator file.  
   And one will be given to the patient. 
•  Electronic data media are to be clearly marked with the trial number/data type/date/hard- and   
   software information (readability). 
•  All trial documents drawn up or available in paper form (e.g. raw data on data forms, CRFs, 
   informal papers, printouts, etc.) are to be uniformly labeled with the trial number/screening 
  number/data type/measurement time point and/or time/date/initials of the staff member. 
•  Clinical research associate (CRA) will verify all data entered into eCRFs for completeness   
   and accuracy with reference to the source documents and records and will issue manual  
CCI, PPD

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   data queries to correct missing data or discrepancies found against the source within the  
   EDC system. 
•  Data validation will consist of automated and manual edit checks that are created directly  
   in EDC. Automated edit checks will be executed on all data points defined and documented    
   by the trial team and data management. 
•  Any changes from the clinical trial protocol in trial planning or execution after submission of the 
   final version of the clinical trial protocol that have ethical or medical implications are to be  
   documented as a „Substantial amendment to clinical trial protocol,“ including cause, content, 
   grounds, consequences, date and the signature of the sponsor and investigator. Such an  
   amendment must be submitted to the appropriate ethics committee(s)/competent authority(ies)  
   for approval. All staff involved in the trial will be informed by the clinical trial manager and  
   investigator. Changes in the clinical trial protocol are only allowed after prior consultation with  
   the person in charge of the trial at the sponsor (clinical trial manager). Changes without ethical  
   or medical implications are to be documented as non-substantial amendments or file notes  
    including date and signature of the sponsor and the responsible person at bioskin. 
•  After all data have been verified by the CRA, an investigator or sub-investigator is required to  
   review and approve all eCRFs prior to database lock and breaking of the blind. 
•  After database lock, each site will be provided with the eCRF data from their site for local 
   archival purposes. 
•  After the conclusion of the trial, the original trial documents (TMF, CRFs) are to be submitted  
   to the sponsor according to the agreements made. 
•  Currently the statutory period for archiving the documents after conclusion of the trial is at least 
   15 years. 
8.1 
Primary source documents 
The investigator must maintain primary source documents supporting significant data for each 
patient’s medical notes.  
All applicable trial data collected on each patient will be recorded by trained site personnel into 
the source data record and the eCRF. Only authorized site personnel will be able to 
enter/modify/correct data to the eCRF. 
Source documents such as the medical records are to be maintained separately from the eCRF 
to allow data verification. Because of the potential for errors, inaccuracies, and illegibility in 
transcribing data onto eCRFs, originals of laboratory and other test results must be kept on file 

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with the patient’s source documentation. The investigator must also retain all patient-specific 
printouts/reports of tests and procedures performed as a requirement of the trial. During 
monitoring visits the monitor will validate eCRF entries against these sources of data. 
eCRFs, source documents, and copies of test results must be available at all times for inspection 
by the trial monitor, auditors, or regulatory inspectors. The following should also be available for 
review 
 
Patient screening log, which should reflect the reason any patient screened for the trial 
was found to be ineligible; 
 
Site personnel and delegation log, which will list all site personnel with their responsibilities 
as delegated by the investigator and their signatures. This log will be maintained at the 
site throughout the trial; 
 
Monitoring visit log, which will list the date and purpose of all monitoring visits by the 
sponsor or designee; 
 
Enrollment log, which will list patient initials and start and end dates for all enrolled 
patients; 
 
Drug inventory/Packing slip, which will list the total amount of drug shipped to the site and 
received and signed for by the investigator; 
 
IMP dispensing log, which will list the total amount of IMP dispensed to and returned by 
each patient; 
 
ICF which must be available for each patient and be verified for proper documentation. 
Following the specific patient information, consent forms will be signed by the patient and 
the physician responsible for supplying information twice. One will be filed in the 
investigator file.  And one will be given to the patient; 
 
All correspondence. 
9. 
Statutory regulations and GCP 
This clinical trial will be conducted in compliance with the protocol. Planning and execution of this 
clinical trial are subject to globally accepted standards of good clinical practice (as defined in the 
ICH E6 (R2) guideline for good clinical practice, November 2016), in agreement with the 
Declaration of Helsinki and in keeping with local regulations. 

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9.1 
Ethics committee/competent authorities 
Before the start of the trial, the clinical trial protocol, informed consent document, and other 
appropriate documents will be submitted to the appropriate ethics committees (ECs) and 
competent authorities (CAs). The trial must not start before approval has been granted by the 
appropriate EC and no grounds for non-acceptance have been issued by the CA concerned.  
9.2 
Insurance 
Insurance policy will be provided for each country participating in the study in accordance with 
local regulations.  
In Germany every patient participating in the clinical trial will be insured in accordance with § 40 
paragraph 3 of the German drug law against injuries to health which may occur during the trial. 
Excluded from this however are injuries to health and deteriorations of illnesses already in 
existence which would have occurred or continued to exist even if the patient had not taken part 
in the clinical trial. 
The insurance cover is jeopardized if the patient fails to report immediately to the investigator or 
responsible physician any injury to health which might have resulted from participation in the 
clinical trial, or if he/she undergoes any other medical treatment without their consent before the 
clinical trial has been completely finished - insofar as the individual patient is concerned. 
Any injury to health which might have occurred as a result of participation in the clinical trial must 
be reported by the patient to the insurer without delay. The investigator is obliged to make such 
a report in any case. 
The patient insurance will be arranged by bioskin GmbH on the basis of the final version of the 
patient information and informed consent form. The patient insurer is 
 
. 
The insurance policy number is 
.  
9.3 
Patient instruction and consent forms 
Every patient will receive a complete and comprehensive explanation of the significance, nature, 
extent and possible risks of the trial. To this end a detailed, written patient information sheet will 
be made available. In addition a physician will carry out an oral information session during which 
the patients will be given sufficient time and opportunity to clarify remaining questions. Two 
identical forms for written informed consent will be given to the patients for signature. One copy 
of the signed forms will be archived in the investigator file and the other retained by the patient. 
CCI
CCI

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The investigator will acknowledge instruction of every patient in accordance with the clinical trial 
protocol and the existence of a signed consent form. 
9.4 
Data protection 
During the clinical trial medical and personal information (like age, gender, racial, and ethnic 
origin) will be collected at the site and documented in the personal file or electronically saved. In 
addition, important data for the clinical trial (including photos and PK data of the subgroups) will 
be saved pseudonymized, transferred, and evaluated. 
If necessary, the collected and saved data (including the photos and PK data) during the clinical 
trial will be held for inspection by the supervisory authority or by people charged by the sponsor 
who check that the trial is done properly. If needed, the related data will be shared pseudonymized 
to: 
 
The sponsor or sponsor-appointed party for the purpose of scientific analysis; 
 
The applicant and the authority responsible for marketing authorization, in case that 
application for marketing authorization is requested; 
 
Sponsor and the responsible competent authority, which will also forward the data to the 
European database, in case of adverse events of the trial drug; 
 
Parties in Europe and in non-European foreign countries which are affiliates of the 
Sponsor and as well forwarded to the responsible authorities in charge of marketing 
authorization by the latter. 
 
Personal and medical data collected during the trial may be moved, stored and used in the EU or 
another country where the sponsor or those working with the sponsor located. Data – including 
trial results – might be published in Scientific Journals, Conference abstract, etc. The trial and 
trial data will be published in clinicaltrials.gov. 
9.5 
Termination of participation 
Every patient has the right to refuse further participation in the trial at any point in time and without 
giving reasons. Nonetheless, efforts should be made to find out the cause and to document it on 
the case report form. If the administration of the investigational product has already taken place 
at the time of refusal, the patient should be convinced to consent to a complete final examination 
as planned in the protocol in his/her own interest. This has to be documented on the 
corresponding pages of the eCRF.  

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9.6 
Quality control (Trial monitoring) 
According to bioskin quality management procedures internal quality control will be applied to all 
steps of the trial e.g. planning, conduct, analysis and reporting.  
A representative of sponsor or bioskin will monitor the trial progress as regularly as necessary 
during the conduct of the trial until the last case report forms have been completed and all queries 
have been resolved.  
The trial and site activities will be monitored according to the ICH-GCP guidelines for: 
 
Protocol adherence (trial is conducted in accordance with the currently approved 
protocol and any other trial agreements) 
 
Quality of data (data are authentic, accurate, and complete) 
 
Drug accountability 
 
Protection of safety and rights of patients 
 
Compliance with regulatory requirements (trial is conducted in accordance with GCP, 
and all applicable regulatory requirements) 
 
Adequacy of the facilities (unchanged high qualification of the site and site staff)  
The investigators and the head of the medical institutions (where applicable) agree to allow the 
monitor direct access to all relevant documents. 
9.7 
Quality assurance 
To ensure compliance with GCP and all applicable regulatory requirements Sponsor may conduct 
a quality assurance assessment and/or audit of the site records at any time during or after 
completion of the trial. 
Auditing will be performed by or on behalf of Quality Assurance MetrioPharm in accordance with 
the requirements of Note for Guidance on Good Clinical Practice, the clinical trial protocol, 
applicable standard operating procedures and according to the agreed audit plan. 
All audit activities in the course of MP1032-CT04 will be documented and archived. 
Independent of any sponsor audit the regulatory agencies may conduct a regulatory inspection at 
any time during or after completion of the trial. 
In the event of an assessment, audit or inspection, the investigators (and institutions) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and to 
allocate their time and the time of their staff to discuss the conduct of the trial, any findings/relevant 
issues and to implement any corrective and/or preventative actions to address any findings/issues 
identified. 

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9.8 
Handling of investigational medicinal products 
The investigator or his representative confirms receipt of the IMPs in writing and will only use 
them within the framework of this clinical trial and in accordance with the existing clinical trial 
protocol. All containers opened, together with remaining contents and unopened containers will 
be returned to the manufacturer at the end of the trial.  
Delivery, consumption and return must be completely documented.  
A written explanation must be compiled on any containers/investigational products which are 
missing. The investigational products will be stored in a safe place according to the 
manufacturer’s instructions for storage. 
The investigator is responsible for ensuring appropriate storage and control of the IMPs. Storage 
records, including temperature records should be maintained and be available for inspection 
during the course of the trial.  
Deviations in storage requirements should be reported to the CRA, the bioskin CTM and to the 
sponsor and may require that the IMP is quarantined during the review of the deviation. 

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11. 
Literature 
 
[1] 
Nast A. Boehncke WH. Mrowietz U et al. S3-Leitlinie zur Therapie der Psoriasis vulgaris 
Update 2011. JDDG; 2011; 9 (Suppl. 2):S1-S104. 
[2]  
EMA Guideline on Psoriasis. Guideline on Clinical Investigation of Medicinal Products 
Indicated for the Treatment of Psoriasis. Issued by the European Medicines Agency, 
London,18 November 2004. Accessed 27 Jan 2016. 
[3] 
MetrioPharmAG. Investigator’s Brochure MP1032. Edition No. 5. 18. Sep 2017. 
[4] 
World Health Association Declaration of Helsinki. Ethical Principles for Medical Research 
involving Human Patients. Adopted by the 18th WMA General Assembly, Helsinki, 
Finland, June 1964, and amended by the 48th WMA General Assembly, Somerset West, 
Republic of South Africa, October 1996. 
[5] 
Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95). The European Agency 
for the Evaluation of Medicinal Products (EMEA) 2002;1-59. 
[6] 
Grekin SJ, Ellis CN. Evaluating the severity of dermatologic disorders. Dermatol Ther 
2009;22(3);191-198. 

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women. 
c) 
Only performed in a subgroup of approx. 2 sites (approx. 30 patients); on Day 1 Photographic   
              documentation will be performed prior to the first administration of IMP 
d) 
Only performed in a subgroup of approx. 2 sites (approx. 30 patients); on Day 1 and Day 84 first PK  
sample will be performed prior to the first administration of IMP. PK samples will be collected before IMP 
administration, and 15, 30, 60 and 120 minutes after administration of IMP. 
e) 
IMP administration will start on Day 1 after randomization and will continue as self- 
administration by trial patients at home until Day 84. Patients included in the PK analysis will administrate 
the first treatment (Day 1) at the site. All patients will administrate the last treatment (Day 84) at the sites. 
f) 
AE reporting starts after the signature of informed consent form and finishes at the End of Study Follow-Up  
Visit. 
 
 
 
 
 
 
 
 
 
 

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Appendix B Psoriasis Area Severity Index (PASI) 
 
Shown below is the original description of the PASI (Fredriksson T, Pettersson U. 
Dermatologica 1978;157:238-44) which involves the assessment of erythema (E), 
infiltration (I), and desquamation (D), and body surface area involvement (A) over 4 
body regions (head (h), trunk (t), upper (u) and lower (l) extremities). 
Degree of severity (per body region) 
Value given 
No symptoms 
0 
Slight 
1 
Moderate 
2 
Marked 
3 
Very marked 
4 
 
Surface involved (per body region) 
Value given 
<10% 
1 
10-29% 
2 
30-49% 
3 
50-69% 
4 
70-89% 
5 
90-100% 
6 
 
Because the head, upper extremities, trunk, and lower extremities correspond to 
approximately 10, 20, 30, and 40% of body surface area, respectively, the PASI score is 
calculated by the formula: 
PASI  =  0.1(Eh + Ih +Dh)Ah + 0.2(Eu + Iu + Du)Au + 0.3(Et + It + Dt)At + 0.4(El +Il 
+Dl)Al 
 

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The protocol amendment 1 contains the following modifications to the original trial design: 
 
 
 
Change and rationale: 
 
Changes due to recruitment of subjects of PK samples 
 
In section 5.5.1.5 (PK samples) the number of PK sites has been changed from 2 (one in 
each country) to approximately 4 (two in each country).  
 
Changes due to administrative reasons: 
 
On page 09 (signatures) the name o
 has been changed to 
 
. 
 
In section 5.5.1.5 (PK samples) the address of the PK laboratory has been changed since 
the laborytory has been moved within the city. 
 
Both Medical Monitors are mentioned in table 6. 
 
PPD
PPD

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Changes to the protocol text due to conditions noted by the ethics committee 
The following text changes will be implemented:  
Page: 9 
Responsible person for SAE notifications: 
Old text:  
 
 
 
 
 
 
 
New text: 
 
 
 
 
 
 
 
 
 
Page: 38 
5.5.1.5 PK samples 
Old text:  
To evaluate systemic concentrations of MP1032 PK samples will be analyzed in a subgroup at 
two selected trial sites (one in Germany and one in Poland; approximately 30 patients in total).  
 
New text: 
To evaluate systemic concentrations of MP1032 PK samples will be analyzed in a subgroup at 
selected trial sites (approximately two in Germany and two in Poland; approximately 30 patients 
in total).  
 
 
 
 
 
CCI, PPD
CCI, PPD

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Page: 38 
Old text 
Samples will be analyzed at: 
  
 
 
 
  
 
New text  
Samples will be analyzed at: 
  
 
 
 
  
 
  
 
Page: 50 
Old text: 
SAE reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
New text: 
SAE reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
CCI, PPD
CCI, PPD
CCI, PPD
CCI, PPD

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Responsible person for SAE notifications: 
  
 
 
 
 
 
 
 
SAE reporting to:  
  
 
 
 
CCI, PPD
CCI

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Table of Content 
Tables ....................................................................................................................................... 12 
1. 
Abbreviations ..................................................................................................................... 13 
2. 
Introduction ........................................................................................................................ 15 
3. 
Risk-benefit evaluation ....................................................................................................... 16 
3.1 
Stress/risks due to trial procedures ........................................................................... 16 
3.2 
Stress/risks due to the investigational medicinal product (IMP) ................................. 17 
4. 
Trial objectives/endpoints ................................................................................................... 19 
5. 
Investigational plan ............................................................................................................ 21 
5.1 
Overall trial design and plan - description .................................................................. 21 
5.2 
Discussion of trial design, including the choice of control groups .............................. 21 
5.3 
Selection and discontinuation/withdrawal of patients ................................................. 22 
5.3.1 Selection of patients ...................................................................................... 22 
5.3.2 Inclusion criteria ............................................................................................. 23 
5.3.3 Exclusion criteria............................................................................................ 24 
5.3.4 Restrictions during the clinical trial ................................................................. 27 
5.3.5 Removal of patients from therapy or assessment .......................................... 27 
5.3.6 Definition of end of trial .................................................................................. 28 
5.4 
Treatments ................................................................................................................ 29 
5.4.1 Treatments to be administered (manner and dose selection) ......................... 29 
5.4.2 Identity of investigational medicinal products ................................................. 30 
5.4.3 Assignment of treatments and randomization ................................................ 31 
5.4.4 Blinding and Breaking the Blind ..................................................................... 31 
5.4.5 Prior and concomitant therapy ....................................................................... 32 
5.4.6 Treatment compliance ................................................................................... 33 
5.5 
Efficacy and safety variable(s)................................................................................... 33 
5.5.1 Procedures .................................................................................................... 33 
5.5.2 Measurement of safety parameters ............................................................... 39 
5.5.3 Vital signs ...................................................................................................... 40 
5.5.4 Smoking and alcohol consumption ................................................................ 40 
5.5.5 Physical examination ..................................................................................... 41 
5.5.6 Appropriateness of assessments ................................................................... 41 
6. 
Data analysis and statistics ................................................................................................ 42 
6.1 
Generation of data base ............................................................................................ 42 
6.2 
Analysis sets and type of analysis ............................................................................. 42 
6.3 
Hypotheses ............................................................................................................... 43 
6.4 
Rationale for the sample size .................................................................................... 43 
6.5 
Statistical methods .................................................................................................... 43 
6.5.1. Efficacy analyses ........................................................................................... 44 
6.5.2. Safety analyses ............................................................................................. 44 
6.5.3. Other analyses .............................................................................................. 45 

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6.6 
Handling of dropouts and missing data ..................................................................... 45 
6.7 
Identification of source data ...................................................................................... 45 
7. 
Adverse events .................................................................................................................. 46 
7.1 
Evaluation of adverse events .................................................................................... 46 
7.2 
Definition of serious and nonserious adverse events ................................................. 47 
7.3 
Reporting/documentation of adverse events ............................................................. 48 
7.3.1 Reporting of adverse events .......................................................................... 48 
7.3.2 Reporting of serious adverse events .............................................................. 50 
7.4 
Pregnancies .............................................................................................................. 51 
8. 
Case report form (CRF), documentation and archiving ....................................................... 51 
8.1 
Primary source documents ........................................................................................ 52 
9. 
Statutory regulations and GCP ........................................................................................... 53 
9.1 
Ethics committee/competent authorities .................................................................... 54 
9.2 
Insurance .................................................................................................................. 54 
9.3 
Patient instruction and consent forms ........................................................................ 54 
9.4 
Data protection .......................................................................................................... 55 
9.5 
Termination of participation ....................................................................................... 55 
9.6 
Quality control (Trial monitoring) ............................................................................... 56 
9.7 
Quality assurance ..................................................................................................... 56 
9.8 
Handling of investigational medicinal products .......................................................... 57 
10. Trial administrative structure/responsibilities ...................................................................... 58 
11. Literature ............................................................................................................................ 59 
Appendix A Trial flow chart 
Appendix B PASI 

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Tables  
 
Table 1: Objectives and endpoints 
Table 2: Prior treatment  
Table 3: Details of the IMPs  
Table 4: Laboratory parameter per visit 
Table 5: Vital signs ranges 
Table 6: Trial administrative structure/responsibilities 
 
 
 

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1. 
Abbreviations 
ADP 
 
Adenosine diphosphate ribose 
ADR 
 
adverse drug reaction 
AE 
 
adverse event 
ALT 
 
alanine aminotransferase 
AMG  
German drug law (Arzneimittelgesetz)  
AST   
aspartate aminotransferase 
AUC 
 
area under the curve 
BfArM 
Federal institute for drugs and medical devices (Bundesinstitut fuer Arzneimittel und 
Medizinprodukte) 
BMI 
 
body mass index 
CA 
 
competent authority 
CMH  
Cochran-Mantel-Haenszel 
CRF 
 
case report form 
EC 
 
ethics committee 
ENT 
 
Ear nose throat 
EoS 
 
End of study 
EoT 
 
end of treatment 
FAS 
 
full analysis set 
(c)-fms  
colony-stimulating factor-1 receptor 
GCP  
good clinical practice 
GMP  
good manufacturing practice 
GOT  
glutamic oxaloacetic transaminase 
GPT 
 
glutamic pyruvic transaminase 
HIV 
 
human immunodeficiency virus 
HRT 
 
hormone replacement therapy 
IB 
 
investigator's brochure 
ICH 
 
international conference on harmonisation 
IL-6 
 
interleukin-6 
IMP 
 
investigational medicinal product 
IMPD  
investigational medicinal product dossier 
ITT 
  
intent-to-treat 
IWRS  
Interactive Web Response Systems 
MCH  
mean corpuscular hemoglobin 
MCHC  
mean corpuscular hemoglobin concentration 
MCV  
mean corpuscular volume 
MedDRA 
medical dictionary for regulatory activities 
PARP-1 
poly(adenosine diphosphate [ADP]-ribose) polymerase 1 
PP 
 
per-protocol 
PT 
 
preferred term 
PV 
 
Pharmacovigilance 
RBC 
 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis system 
SES 
safety evaluation set 
SGK-2 
serine / threonine-protein kinase 
SOC 
system organ class 
SUSAR 
suspected unexpected serious adverse reaction 

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TACE 
metalloprotease TNF-α converting enzyme 
TEAE 
treatment emergent adverse event 
TMF 
 
trial master file 
TNF-α  
Tumor Necrosis Factor α 
VCS 
 
valid cases set 
WBC  
white blood cell 
WCBP  
women of childbearing potential 
WHO  
world health organization 

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2. 
Introduction 
MP1032 is a small-molecule macrophage modulator currently not available as a registered or 
approved medicinal product within the borders of the European economic area, the United States, 
or Japan. Experimental data have shown that MP1032 can inhibit inflammation by reducing Tumor 
Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) [1]. MetrioPharm AG is developing MP1032 as 
an anti-inflammatory compound. The first target indication is psoriasis. 
Psoriasis is a relatively common skin condition, affecting 1.5 to 3% of the general population in 
Europe [2]. Psoriasis can have a particularly negative effect on quality of life, affecting a sufferer’s 
physical, social, and psychological functioning so the need for effective therapies is high. 
Psoriasis is characterized by outbreaks of skin inflammation interspersed by varying periods of 
remission. The underlying mechanisms of the inflammatory flares in psoriasis are poorly 
understood, but the therapeutic potency of anti-TNF- α and anti-IL-17 biologics is evidence of 
immune modulation’s potential to reduce disease severity [1]. 
However, antibody-based biologics therapies are not optimal therapies for life-long treatment of 
psoriasis, due to decreasing efficacy over time and relatively high costs. Furthermore, the use of 
immune-suppressive drugs, such as methotrexate, cyclosporine, or anti-TNF-α/IL-12/IL-17/ IL-23 
biologics increases the risk of opportunistic infections and/or requires regular laboratory checks 
on blood and liver function [1]. 
MP1032 has been shown to reduce TNF-α and IL-6 levels in vitro (human peripheral blood 
mononuclear cells and differentiated human promyelocytic leukemia cells), and in vivo, and its 
anti-inflammatory potential has been shown in mouse and rat arthritis models. Other anti-
inflammatory compounds usually exhibit immune-suppressive effects resulting in an increased 
vulnerability to infections. MP1032, on the other hand, has shown an anti-infective potential in 
animal infection models. 
The mechanism of action is thought to be mediated by MP1032’s partial inhibition of the enzyme 
poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP-1), the kinases human Aurora-B, 
human Aurora-C, serine / threonine-protein kinase (SGK-2), tyrosine kinase (colony-stimulating 
factor-1 receptor [c-fms / FMS], and the metalloprotease TNF-α converting enzyme (TACE, also 
known as ADAM17).  
As a multi-target small-molecule macrophage modulator, MP1032 seems to avoid the problems 
of tolerance and reduced long-term efficacy that biologics have. An important potential safety 
advantage of MP1032 lies in the observation from animal models that the compound reduces 
rather than increases susceptibility to bacterial and viral infections. This may be due to the fact 
that MP1032 is reducing – rather than completely suppressing – TNF-α and IL-6 levels. 

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MetrioPharm considers these molecular and safety characteristics along with the ease of an oral 
therapy over topical therapies as strong arguments for MP1032 to become an effective therapy 
option in moderate-to-severe psoriasis, where topical agents are not effective enough or too 
tedious for patients to apply them regularly. 
MP1032 has been assessed in a phase I first-in-man clinical trial. In part 1 of this trial (single-
ascending doses), 12 volunteers were administered 50 to 600 mg MP1032. One mild adverse 
drug reaction (ADR) of “headache” was classified as related to the investigational medicinal 
product (IMP) and was reported after treatment with 50 mg MP1032. In part 2 of the clinical trial, 
general safety and tolerability of MP1032 were assessed in multiple ascending doses. No ADRs 
were reported in part 2, in which the volunteers received 2 × 100 mg per day and 2 × 300 mg per 
day at 12-hour intervals for 7 consecutive days. 
Subsequently, an exploratory, double-blind, parallel phase IIa trial to evaluate the safety, 
pharmacokinetics and efficacy of orally administered MP1032 in patients with moderate to severe 
chronic plaque psoriasis was performed. A total of 44 patients were randomized with a 1:1 ratio 
to either receiving 100 mg MP1032 twice daily or placebo for 42 days. The findings of that trial 
shows that after only six weeks of treatment, there is a clinically meaningful response in patients 
who entered the trial with a PASI score of 10-20 and achieved appropriate MP1032 exposure 
values. As MP1032 is well tolerated, further studies using higher doses of MP1032 and longer 
treatment durations need to be conducted to fully evaluate the efficacy of MP1032 for the 
treatment of moderate to severe psoriasis. 
Further details can be found in the Investigator's Brochure (Edition 5, September 2017), which 
contains comprehensive information on the IMP [3]. See Section 5.1 for details concerning the 
design of the current trial and section 5.2 for justification of the design of this trial. 
3. 
Risk-benefit evaluation 
3.1 
Stress/risks due to trial procedures 
The noninvasive procedures (clinical assessments and photographic documentation) do not pose 
a risk or stress for the patients.  
The blood sampling procedure poses the same very small risk as normally associated with this 
procedure (e.g. infection, bleeding into the surrounding tissue, and very rarely inflammation of the 
vein or formation of blood clots). Therefore blood withdrawal will only be conducted by qualified 
medical personnel. 

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3.2 
Stress/risks due to the investigational medicinal product (IMP) 
General safety and tolerability of MP1032 has been assessed in one phase 1 first-in-man 
clinical trial. In the single ascending doses part of this trial, twelve volunteers were administered 
50 to 600 mg MP1032. One mild ADR (“headache”) was reported once after treatment with 50 
mg MP1032 in one volunteer. No ADRs were reported in the multiple ascending doses part 
where volunteers received 2×100 mg per day and 2×300 mg per day at 12-hour intervals for 
seven consecutive days.  
In a previous IIa trial following TEAEs were observed: In summary the number of patients with 
TEAEs was 14 (60.87%, 27 TEAEs) in the MP1032 group and 15 (65.22%, 32 TEAEs) in the 
placebo group. The most commonly reported TEAEs were in the SOC categories of infections 
and infestations (5 patients [21.74%] in the MP1032 group and 8 patients [34.78%] in the 
placebo group) and nervous system disorders (7 patients [30.43%] in the MP1032 group and 3 
patients [13.04%] in the placebo group). No clinically important differences were seen between 
the two treatment groups with regard to the number and overall pattern of patients reporting 
TEAEs by System Organ Class (SOC). 
A positive phototoxic signal detected in non-clinical studies could be indicative of a likely clinical 
phototoxic risk of MP1032, although the risk for the patients seems to be unlikely and no 
associated TEAEs were seen in the previous clinical trials. Nevertheless, psoriasis patients 
participating in this trial should be advised to minimize sun exposure (sun bathing) and strong UV 
exposure (see also inclusion criterion No. 9). Furthermore, the use of sunscreen will be 
recommended when spending an extended period of time outdoors. The latter requirement will 
be valid during the whole 12 weeks of treatment duration plus the 4 weeks of follow up period. 
Women of childbearing potential (WCBP) must agree to use a highly effective contraceptive 
method (Pearl-Index < 1%) starting at screening and continuing throughout the clinical trial period 
and for 28 days after final IMP administration. 
Highly effective forms of birth control (according to International Conference on Harmonization 
[ICH] M3) have low failure rates (i.e. less than 1% per year) when used consistently and correctly, 
and include the following: 
 
The male partner of a female patient has undergone effective surgical sterilization. 
 
A female patient can use an established oral contraceptive, injected or implanted 
hormonal methods of contraception or an established intrauterine device or 
intrauterine system. 

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True sexual abstinence as a form of birth control will be allowed in the trial when this is in 
accordance with a patient’s preferred and common lifestyle. Periodic abstinence (e.g. calendar, 
ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of 
a trial, and withdrawal are not acceptable methods of contraception. Patients who use abstinence 
as a form of birth control must agree to abstain from heterosexual intercourse from the month 
prior to screening until 28 days after the last dose of IMP (or longer if required by local 
regulations). Study personnel must confirm the continued use of abstinence is still in accordance 
with the patient’s lifestyle at regular intervals during the trial. 
Post-menopausal is defined as 12 months of spontaneous amenorrhea. Females who have 
been sterilized, or had a hysterectomy, may be included. 
A sterile woman is defined by either of the following medical interventions performed before 
intake of IMP 
 
Tubal ligation, or 
 
Bilateral oophorectomy, or 
 
Total hysterectomy. 
If documented, women with one of these conditions are not required to use additional 
contraception. 
 
Male patients who are sexually active with a female partner and are not surgically sterile 
(vasectomy performed at least six months prior to treatment) must agree to inform their female 
sexual partner about his trial participation and to use an acceptable form of birth control as 
described in the informed consent form. Prior to trial enrollment, patients must be advised of the 
importance of avoiding pregnancy during trial participation and the potential risk factors for an 
unintentional pregnancy. The patient must sign an informed consent form documenting this 
discussion. 
Against these minimal risks stands the benefit of information on the efficacy and safety of a 
promising new substance which is intended to be used in the oral administration in patients with 
psoriasis vulgaris.  
Taking into account these risks and benefits, the performance of the trial can be considered 
ethically sound since the expected benefits of the IMPs appear greater at present than the risks 
for the patients. The clinical trial protocol will be submitted to the responsible ethics committee(s) 
for approval. 

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5. 
Investigational plan 
5.1 
Overall trial design and plan - description 
This trial is a randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy 
and safety of two oral doses of MP1032 (150 mg bid and 300 mg bid) in adult patients with 
moderate-to-severe chronic plaque psoriasis. 
The trial design consists of a 28-day screening period, a 12-week treatment period, and 
subsequently a 28-day follow-up period. Each patient will have 6 visits and unscheduled visits as 
needed. 
Approximately 150 patients (2 × 50 patients MP1032 and 50 patients placebo) who meet the entry 
criteria will be randomized on Day 1 to receive either 150 mg MP1032, 300 mg MP1032 or 
placebo orally twice daily for 12 weeks. The administration of IMP will stop after end of study (in 
max. 13 weeks). Recruitment will be competitive between the sites but enrollment will be limited 
to 12 patients per site. A recruitment of more than 12 patients may be allowed after sponsor 
approval.  
Safety parameter will be monitored from the signing of the informed consent form (ICF) until the 
last follow-up visit. 
Efficacy and safety will be assessed as outlined in the trial flow chart. 
5.2 
Discussion of trial design, including the choice of control groups 
Pre-clinical toxicology studies, a Phase I single plus multiple ascending dose trial, as well as an 
exploratory Phase IIa pilot trial of oral MP1032 have indicated a higher degree of safety and 
tolerability of the IMP compared to all currently used systemic psoriasis treatments. Moreover, a 
first assessment of oral MP1032’s clinical efficacy in moderate-to-severe psoriasis in the 
preceding Phase IIa trial has shown clinically meaningful response in patients who entered the 
trial with a PASI score of 10-20 during six-week treatment period. 
In several animal models of chronic, immune-mediated inflammatory diseases, MP1032 has been 
shown to have a pronounced anti-inflammatory effect. 
The primary objective - to evaluate clinical efficacy and safety of MP1032 in patients with psoriasis 
during the 12-week treatment period and a 4-week follow up - will provide an opportunity to 
perform oral MP1032’s clinical efficacy in moderate-to-severe psoriasis when taken for twice as 
long as done in Phase IIa.  

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On the basis of pre-clinical, Phase I and Phase IIa data, the current trial was also designed to 
assess the safety and tolerability of oral MP1032 over a period of 12 weeks, trying to reproduce 
the excellent tolerability and safety profile that was seen in Phase I and Phase IIa (up to 7 days 
and 6 weeks, respectively), over a longer period of time.  
The extension of treatment to 12 weeks and a 4-week follow-up observation period will give the 
opportunity to obtain even more meaningful safety data and more comprehensive data on 
efficacy.  
To evaluate systemic concentrations of MP1032 PK samples will be analyzed in a subgroup. 
The photographic documentation will only be used for visual demonstration of efficacy. No 
assessments will be performed using this data. 
Patients will be randomized to one of three treatment arms (MP1032 600mg, MP1032 300mg or 
placebo) in a blinded manner. The treatment allocation will be on a 1:1:1 ratio (50:50:50 patients). 
Recruitment will be competitive between the sites but enrollment per site will be limited to 
12 patients (more than 12 patients needs to be approved by the sponsor).  
5.3 
Selection and discontinuation/withdrawal of patients 
5.3.1 Selection of patients 
The selection of patients is in accordance with the requirements of the national laws as well as 
the recommendations of the currently valid revision of the Helsinki Declaration [4] and the ICH 
GCP guideline [5]. Advertisement (e.g. newspaper, online portal, bus or metro) will be used only 
after positive approval by the responsible EC.  
The trial population will consist of approx. 150 patients (planned 75 Germany and 75 Poland) with 
moderate-to-severe chronic plaque psoriasis. Patients must be able to provide written consent 
and meet all the inclusion criteria and none of the exclusion criteria. 
A gender specific subdivision into groups is not necessary in this clinical trial. Male or female 
patients between 18 years and 70 years are eligible for this clinical trial insofar that they suffer 
from moderate-to-severe-psoriasis. The antipsoriatic efficacy is likewise detectable in men and 
women. 

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5.3.2 Inclusion criteria 
All of the following criteria have to be met for inclusion of a patient in this trial: 
1. Participants legally competent to sign and give informed consent.  
2. Adult male and female patients between 18 years and 70 years with moderate-to-severe 
chronic plaque psoriasis (diagnosed by Investigator): 
a) PASI score ≥10 - ≤20 at baseline  
b) BSA score: > 10% 
c) Stable disease duration of ≥ 6 months at the initiation of IMP. 
d) topical therapy fails to control the disease 
3. Body Mass Index (BMI) between 18.5 and 34.9 kg/m2. 
4. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at 
Screening (Visit 1). In addition, sexually active WCBP must agree to use adequate 
contraception throughout the trial (see Section 3.2 for more details on adequate 
contraception): 
a) A method with less than 1% failure rate OR 
b) Abstinence 
5. Post-menopausal women with spontaneous amenorrhea for at least 12 months and 
women on hormonal replacement therapy (HRT). The use of hormonal replacement 
therapy (HRT) during the trial is permitted, however for these patients an appropriate 
contraception method according to Inclusion Criterion 4 must be ensured. Sterilized 
women may be included (see Section 3.2 for more details on sterile definition) 
6. Male patients who are sexually active with a female partner and are not surgically sterile 
(vasectomy performed at least six months prior to treatment) must agree to inform their 
female sexual partner to use an acceptable form of birth control as described in the 
informed consent form. For females, an acceptable method (Pearl Index < 1%) would be 
to use implants, injectable, combined oral contraceptives, some intrauterine devices, or 
be postmenopausal, be surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy) 
7. In good health as judged by the investigator, based on medical history, physical 
examination, serum chemistry, hematology and urinalysis 
8. Patients must meet the following clinical laboratory criteria: 

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 
White blood cell count ≥3.5 × 109/L 
 
Platelet count ≥100 × 109/L 
 
Serum creatinine ≤1.5 × upper limit of normal (ULN); estimated glomerular 
filtration rate >60 mL/min 
 
Total bilirubin ≤1.5 × ULN 
 
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
≤2.5 × ULN 
 
Hemoglobin ≥ lower limit of normal as per central laboratory reference ranges for 
women and men accordingly 
 
No coagulopathy (International Normalized Ratio [INR] <1.5) 
9. Patients agree to minimize normal sun exposure during the course of the trial 
10. Patients are considered reliable and capable of adhering to the protocol (e.g. able to 
understand the patient information and complete diaries), visit schedule, or medication 
intake according to the judgment of the Investigator. 
5.3.3 Exclusion criteria 
Patients are to be excluded from the trial, when one or more of the following conditions are met: 
1. Patients with non-plaque form of psoriasis (erythrodermic, guttate, pustular form of 
psoriasis). Associated psoriasis arthritis is allowed provided no other in-/exclusion criteria 
are influenced, no forbidden concomitant therapy is required for the well-being of the 
patient and there is no impact on trial objectives as determined by the Investigator. 
2. Treatment with concomitant medication that may affect and provoke or aggravate 
psoriasis, e.g. antimalarial drugs, beta-blockers or ACE inhibitors unless on a stable dose 
for 3 months before IMP intake. 
3. Evidence of skin conditions at the time of Screening Visit other than psoriasis that would 
interfere with evaluations of the effect of the IMP on psoriasis. 
4. Patients with any serious medical condition, laboratory abnormality, or psychiatric illness 
that would prevent the patient from signing the ICF, as assessed by the investigator. 
5. Pregnant or lactating women or women planning to become pregnant during the trial 
and / or within 28 days following the last dose of IMP. 

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5.3.4 Restrictions during the clinical trial 
A positive phototoxic signal detected in non-clinical studies could be indicative of a likely clinical 
phototoxic risk of MP1032, although the risk for the patients seems to be unlikely. Nevertheless, 
psoriasis patients participating in this trial should be advised to avoid strong sun exposure (sun 
bathing) and strong UV exposure (see inclusion criterion no. 9). Furthermore, the use of 
sunscreen will be recommended when spending an extended period of time outdoors. During the 
trial patients should adhere to their standard skin care regimen and may use their standard 
emollients/moisturizers as symptoms require but may not use treatments as precluded by the 
exclusion criteria. The latter requirement will be valid during the whole 12 weeks of trial duration 
plus the 4 weeks of follow up period. 
5.3.5 Removal of patients from therapy or assessment 
5.3.5.1 
Criteria for discontinuing the whole clinical trial 
Premature termination of a clinical trial may occur upon decision of the Sponsor, upon decision 
of the Investigator, by request of an authority, or because of withdrawal of positive vote by the 
responsible IEC. If the Investigator, the Sponsor, or the Medical Monitor becomes aware of 
conditions or events that suggest a possible hazard to patients, if the trial continues, the trial may 
be terminated after appropriate consultation between the relevant parties. The trial may also be 
terminated early at the Sponsor’s discretion in the absence of such a finding.  
Conditions that may warrant termination of the trial as a whole include, but are not limited to:  
 
Concerns for safety that arise within this trial or in any other trial with the IMP;  
 
The discovery of an unexpected, significant, or unacceptable risk to the patients enrolled 
in the trial;  
 
Failure to enroll patients at an acceptable rate;  
 
Ethical issues;  
 
Severe non-compliance;  
 
A decision on the part of the Sponsor to suspend or discontinue development of the 
drug.  
5.3.5.2 
Criteria for discontinuing in the case of individual patients 
Patients may withdraw from the entire trial including follow-up at any time without penalty and for 
any reason without prejudice to his or her future medical care. 
The following criteria must lead to discontinuation from the clinical trial in individual patients: 
 
Patient withdraws informed consent 

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 
Pregnancy (see section 7.4) 
 
Severe protocol violations that result in a significant risk to the patient’s safety 
 
Emergence of the following AEs including: 
a) Patient reports symptoms which are considered unacceptable by the patient or the 
Investigator or if any serious AE occurs that is judged as at least possibly related to 
the IMP by the Investigator 
b) Abnormal laboratory value(s) confirmed by repeat measurements: 
 
Elevated liver transaminases (AST/ALT) ≥3 × ULN AND elevated bilirubin 
total bilirubin ≥ 2 × ULN 
 
Elevated serum creatinine ≥2 × ULN 
The following criteria may lead to discontinuation from the clinical trial in individual patients: 
 
Use of prohibited concomitant medication as defined in section 5.4.5. 
 
In all cases, the reason(s) for withdrawal, and the primary reason, must be recorded on the 
electronic data capture (EDC) system / electronic case report form (eCRF). If a patient is 
prematurely withdrawn from the IMP for any reason, the Investigator must make every effort to 
perform the evaluations described for the End of Treatment and Follow-up Visits. The Investigator 
should contact the Medical Monitor, whenever possible, to approve withdrawal of patients in 
advance. 
If a patient withdraws consent and still agrees to undergo a final examination, it will be 
documented on the eCRF and the patient record.  
A patient may also be withdrawn from the IMP by the Sponsor, Regulatory Authorities, or 
Independent Ethics Committees (IECs) / Institutional Review Boards (IRBs). 
Patients who are withdrawn from the trial will be not replaced. 
Protocol violation, failure to comply with the trial stipulations/poor compliance may lead to 
discontinuation from the clinical trial in individual patients. 
5.3.6 Definition of end of trial 
The end of the trial is defined as the last visit of the last patient completing the trial (including 
follow-up visits). 

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5.4 
Treatments 
The IMP will be packed in kits, 1 kit per patient per week. One kit contains 14 blisters and one 
blister contains six, 50 mg, hard gelatin capsules of MP1032 and/or placebo (described below). 
IMP will be packaged and labelled by 
 according to all local legal 
requirements. IMP will be labelled in accordance with applicable regulatory requirements. 
All IMP supplies must be stored at room temperature (15 - 25°C) and protected from light, in 
accordance with the manufacturer’s instructions. Until dispensed to the patients, the IMP will be 
stored in a securely locked area, accessible to authorized personnel only. 
5.4.1 Treatments to be administered (manner and dose selection) 
Once patients have met the trial entry criteria, completed the screening procedures and run-in 
period, and completed the pre-dose procedures and assessments, they will be randomly assigned 
as described in Section 5.4.3 above to one of the three treatment groups described below. They 
will receive total daily doses of 300 mg or 600 mg MP1032 (IMP) or placebo (IMP placebo) as 
follows (1:1:1): 
 
Treatment A: 3 × 50 mg (150 mg) MP1032 plus 3 × placebo hard gelatin capsules 
(per dosage) twice daily for 84 days 
 
 
Treatment B: 6 × 50 mg (300 mg) MP1032 hard gelatin capsules (per dosage) twice 
daily for 84 days 
 
 
Treatment C: 6 × placebo hard gelatin capsules (per dosage) twice daily for 84 days. 
All administrations will take place with at least 8 hours between the dosings. 
CCI

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5.4.2 Identity of investigational medicinal products 
Details of the IMPs are given in the table 3. 
Table 3:Identity of investigational medicinal products: 
Generic name/brand 
name/INN 
Verum 
Placebo 
Formulation  
Hard gelatin capsules, size 3  
The mixture (995 parts mannitol and 5 parts colloidal anhydrous silica) is 
well 
known 
and 
described 
in 
compendia 
(German: 
Neues 
Rezepturformularium, Monographie Nr. S. p. 38.). At least 25% of the mass 
of the contents are active ingredient. Placebo capsules constituted only of 
the excipients described above. 
Active ingredient 
MP1032 
5-Amino-1,4-dioxo-1,2,3,4-
tetrahydrophthalazine-3-id, sodium 
salt 
n.a. 
Amount per unit 
containing 50 mg MP1032 for oral 
administration 
n.a. 
Primary packaging 
Blister 
Blister 
Storage 
room temperature (15 – 25 °C) 
room temperature (15 – 25 °C) 
Manufacturers 
 
 
 
 
 
 
 
 
All IMPs will be labeled according to the requirements of local law and legislation. A copy of the 
labels will be filed in the trial master file (TMF). 
All IMPs used during the trial will be stored at the trial center in accordance with instructions given, 
and will be inaccessible to unauthorized personnel.  
Missing a treatment 
If the patient misses a dose, and remembers the dose within 6 hours of scheduled dosing, he/she 
may take it. If it has been more than 6 hours since the planned dose time, the patient should skip 
the dose. All missing doses should be documented by the patient in the diary. However, all 
administrations will take place with at least 8 hours between the dosings. 
Overdose 
The risk of overdosing in general in this trial is considered to be low due to the maximum dose 
that each patient can receive via six capsules being 150 mg, 300 mg MP1032 or Placebo. 
Nevertheless, unintentional administration of any dose that deviates from the scheduled regimen 
will be documented and reported by site staff via eCRF. In case of overdose symptomatic 
CCI
CCI

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treatment should be provided as indicated and a safety blood analysis should be performed. The 
Sponsor should be informed immediately.  
5.4.3 Assignment of treatments and randomization 
Patient Identification 
Upon signature of informed consent (screening period) each patient receives a 5-digit patient 
identification number, which is composed of: 
Digits 1 and 2: 
trial center (01, 02, 03, etc.) 01 – 10 for German sites and 11 – 20 for 
Polish sites 
 
Digits 3, 4 and 5: 
individual screening number within the center (consecutively in the order 
of screening within the center: 001, 002, etc.)  
 
Treatment Assignment 
 
Patients will be randomized on a 1:1:1 basis to one of three treatment groups: 
 
 
MP1032 300 mg bid 
 
MP1032 150 mg bid 
 
Placebo bid 
 
The trial will use a block randomization scheme. Enrollment will be performed competitively 
between all 14 centers (Germany and Poland) until approximately 150 patients are enrolled in the 
trial in order to have 120 evaluable patients. 
Patients who are eligible for enrollment into the trial will be randomized at Visit 2/Day 1 and will 
be assigned the lowest random number available at the site. Patient kits will be dispensed 
according to the kit number assigned by the IWRS. The kit numbers will be assigned to the 
treatment kits by a simple randomization.  
The treatment group designation will remain blinded until the final database is locked. 
The random list, assigning the randomization number to the treatment groups, and the kit number 
list, assigning the kit number to the treatment groups will be generated by psy consult scientific 
services.  
5.4.4 Blinding and Breaking the Blind 
 
The trial will be performed in a double-blind manner. All IMPs will be supplied in identical form 
and will be similar in color, smell, taste, and appearance.  
The IMPs will be blinded by 
.  
CCI

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The trial blind should not be broken except in case of a medical emergency (where knowledge of 
the IMP received would affect the treatment of the emergency) or regulatory requirement (e.g. for 
SUSAR [in Germany]).  
If the blind is broken via IWRS, the date, time, person who broke the blind and the reason must 
be recorded in the patient’s eCRF, and any associated AE report.  
The treatment code will only be broken after all the clinical database is locked. 
5.4.5 Prior and concomitant therapy 
Any medication the patient takes other than the IMP, including herbal and other non-traditional 
remedies, is considered a concomitant medication. All concomitant medications taken in the 6 
weeks before the first dose must be recorded in the eCRF. The following information must be 
recorded in the eCRF for each concomitant medication: brand name, route of administration, start 
date, stop date, dosage, and indication. Any changes in the dosage or regimen of a concomitant 
medication must be recorded in the eCRF.  
At Screening, patients will be asked which psoriatic treatment they have previously taken (last 6 
weeks) and which other concomitant medications they have taken in the last 6 weeks. At each 
subsequent trial visit, patients will be asked which concomitant medications they are currently 
taking and have taken since the previous site visit. 
For a detailed list of forbidden medication see exclusion criterion 14. 
Medication allowed during the course of the trial: 
 
Topical moisturizers or emollients, UVA/UVB sunscreens, shampoos for scalp psoriasis 
(without tar), as needed.  
 
Contraceptives (see section 3.2) 
 
Any concomitant medication to treat stable diseases (such as well-controlled 
hypertension, hyperlipidemia, etc.) 
Prohibited medication: 
 
All treatment as specified in exclusion criteria. 
Concomitant medications should be kept to a minimum during the clinical trial. However, if these 
are considered necessary for the patient's welfare and are unlikely to interfere with the clinical 
trial objectives, they may be allowed at the discretion of the investigator. For a detailed list of 
forbidden medication see exclusion criterion 14. 

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5.4.6 Treatment compliance 
All treatment administrations (except first for the PK subgroup and last treatment for all patients) 
will be taken by the patients at home. All treatment administrations will be documented in a diary. 
All missing treatment administrations documented in the diary will be counted and documented 
in the eCRF.  
All dispensed kits and blisters (used and unused) will be collected at each visit and capsules will 
be counted at each visit during the treatment period. The results will be documented in the eCRF.  
In case of inadequate usage the patient will be instructed again on application use. 
5.5 
Efficacy and safety variable(s) 
5.5.1 Procedures 
Screening period  
Day -28 to -3 (visit 1)  
Within the 28 days prior to the first IMP administration the volunteer will come to the trial centers 
for the initial screening (including documentation of demographic data). Screening assessments 
will be performed after the volunteer has agreed to participate and has signed and dated the 
informed consent form.  
At screening a serum pregnancy test will be carried out in all female patients. 
The following examinations will be performed: 
 Obtain written informed consent 
 Documentation of relevant medical and relevant surgical history (last 5 years) 
 Documentation of demographic data 
 Documentation of Smoking history/ alcohol consumption 
 Documentation of relevant previous medication (last 6 weeks) 
 Serum pregnancy test and urinalysis (see section 5.5.2) 
 Start check in-/exclusion criteria (see section 5.3.2 and 5.3.3) 
 Physical examination (see section 5.5.5) 
 Height, body weight and BMI 
 Record vital signs (see section 5.5.3) 
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2)  
 BSA (see section 5.5.1.3) 

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 Collection of samples for determination of laboratory parameters (serology, hematological 
status, clinical chemistry, see section 5.5.2). 
Note: Adverse events before start of treatment (i.e. occurring after signature on consent form). 
Patients who have abnormal test results during the screening period may be re-screened if the 
Medical Monitor agrees. 
Experimental phase 
Trial Day 1 (baseline, week 1, visit 2) 
 Re-check of in-/exclusion criteria (see section 5.3.2) 
 Randomization 
 Physical examination (see section 5.5.5) 
 Record vital signs (see section 5.5.3) 
 Urine pregnancy test and urinalysis (see section 5.5.2) 
 Record concomitant medications 
 Record adverse events occurring from the time of informed consent signature 
 Localization of photographic documentation test field only for a subgroup (see section 5.5.1.4) 
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, see section 5.5.2)  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 Dispensing diary  
 Start of PK samples only for a subgroup (see section 5.5.1.5) 
 Dispensing IMP  
 Administration of IMP at site (PK subgroup only)  
 
Trial Day 28 (week 4, visit 3) and Day 56 (week 8, visit 4)  
 Check concomitant therapy and adverse events 
 Record vital signs 
 Drug return / accountability and re-dispensation of unused kits/blister 
 Diary collected and checked  
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Urinalysis (see section 5.5.2) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, urinalysis, see section 5.5.2)  
 PASI (see section 5.5.1.1) 

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 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 Dispensing of IMP and diary 
 
Trial Day 84 (week 12, visit 5) (EoT) 
 Check concomitant therapy and adverse events 
 Physical examination (see section 5.5.5) 
 Record vital signs (see section 5.5.3) 
 Urine pregnancy test and urinalysis (see section 5.5.2) 
 Photographic documentation only for a subgroup (see section 5.5.1.4) 
 Collection of samples for determination of laboratory parameters (hematological status, 
clinical chemistry, see section 5.5.2)  
 PK samples only for a subgroup (see section 5.5.1.5) 
 Last IMP administration at site for all patients 
 Drug return / accountability  
 Diary collected and checked  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 
Trial Day 112 (week 16, visit 6, Follow-up) (End of Study, EoS) 
 
Photographic documentation only for a subgroup (see section 5.5.1.4) 
 
Check concomitant therapy and adverse events 
 
Physical examination (see section 5.5.5) 
 
Record vital signs (see section 5.5.3) 
 
Urinalysis(see section 5.5.2) 
 
Collection of samples for determination of laboratory parameters (hematological status, 
 clinical chemistry, see section 5.5.2)  
 PASI (see section 5.5.1.1) 
 PGA (see section 5.5.1.2) 
 BSA (see section 5.5.1.3) 
 
The patients must be present at site for approximately 60 minutes on Screening and Day 1, 45 
minutes on Day 28 and 56, 60 minutes on Day 84 and 45 minutes on Day 112. 
The above mentioned time will be extended for 15 minutes for patients with photographic 
documentation on each visit.  

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The above mentioned time will be extended on Day 1 and Day 84 for 120 minutes for patients 
with PK sampling.  
 
Early Termination Visit 
Patients who discontinue early from the trial should, if possible, have an Early Termination Visit. 
This visit should take place as soon as possible after the patient stops taking IMP. The 
observations and procedures scheduled for Visit 5 (End of Treatment) should be performed at the 
Early Termination Visit. 
A schedule of trial procedures is provided in appendix A to this trial protocol. 
Unscheduled visit 
The patient may return to the clinic at the discretion of the investigator.  
At this visit, the investigator or designee will:  
• Query the patient about any changes in health status or concomitant medications and therapies 
since the previous visit, and document the findings respectively (AE/concomitant medications)  
• Perform assessments which are relevant to the reason for the unscheduled visit (e.g. 
Photographic documentation, Lab analysis, PASI, PGA, BSA, etc.) 
• Confirm the next visit 
5.5.1.1 
Psoriasis Area Severity Index (PASI)  
The PASI is the most commonly used and validated assessment for grading the severity of 
psoriasis in clinical studies [2]. The PASI is a physician’s assessment of psoriasis that is a 
therapeutic standard in clinical studies for this disease (appendix B). The PASI quantifies the 
severity and extent of the disease and weighs these with the body surface area involvement. It 
involves the assessment of erythema, infiltration, desquamation, and body surface area 
involvement over 4 body regions: head, trunk, upper and lower extremities.  
The Investigator assesses the redness, thickness, and scaliness of lesions on a 5-point scale 
(from 0 = none, through 4 = severe). The percentage of skin involved is scored and transferred to 
a grade (graded 0 to 6; 0 = 0% involved area, 6 = 90%-100% involved area). In addition, the 
percentage of involved body surface area is estimated across 4 body areas, head (10%), upper 
extremities (20%), trunk (30%), and lower extremities (40%). The sum of all 3 severity parameters 
is then calculated for each of the 4 sections of skin, multiplied by the area score for that area, and 
multiplied by the weight of the respective section to give a PASI score, which ranges from 0 to 
72, with a higher score indicating increased disease severity. The PASI will be completed by the 

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Investigator or designee at the time points prior to and following IMP administration as defined in 
the trial schedule. See appendix B for details of calculation. 
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. Initials of the assessor will be documented in the eCRF. 
5.5.1.2 
Physician`s Global Assessment (PGA)  
The PGA provides an overall evaluation of the severity of the disease [6]. The PGA is a 7-point 
physician’s assessment of psoriasis that is a therapeutic standard in clinical studies for this 
disease.  
The Investigator or designee will complete a PGA form to evaluate the disease severity at a single 
time point. Scoring is on a 7-point scale: 0 = clear; 1 = almost clear; 2 = mild; 3 = mild to 
moderate; 4 = moderate; 5 = moderate to severe, and 6 = severe. The PGA will be completed by 
the Investigator (or designee) at the time points specified.  
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. Initials of the assessor will be documented in the eCRF. 
5.5.1.3 
 Assessment of body surface area (BSA)  
The total surface area of the body affected with psoriasis plaques will be determined by the 
Investigator at V2 (Wk0-D1), V3 (Wk4-D28), V4 (Wk8-D56), V5 (Wk12-D84), and V6 (Wk16-
D112). Calculation should include psoriasis on the palms of the hands and soles of the feet as 
well as on the face and scalp. The investigator will calculate the approximate BSA by assuming 
that 1% BSA is approximately equal to the surface area of one outstretched hand (with fingers) 
of the patient [2].  
The assessment of BSA by the Investigator serves to describe the change in % BSA affected by 
psoriasis after 12 weeks of treatment.  
If possible, the same investigator should complete the evaluations for a given patient throughout 
the trial. 
5.5.1.4 
Photographic documentation 
At all visits photographic documentation of one affected area (from trunk, arms or legs) will be 
performed in a patient subgroup at two selected trial sites (one site in Germany and one in Poland; 
approximately 30 patients in total). The target plaque for the photographic documentation will be 
defined before first treatment on Day 1 and should mirror the actual individual psoriasis grade of 

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the patient. The procedure will be described in a separate photographic method manual. Steps 
will be taken to ensure that the identity of the patient is protected to the extent possible. Additional 
consent will be undertaken with regard to collection, transmission, storage and use of images.  
No efficacy or safety assessment will be made using these images. The images will be taken for 
educational and marketing purposes only and might be used in scientific publications. 
5.5.1.5 
PK samples 
To evaluate systemic concentrations of MP1032 PK samples will be analyzed in a subgroup at 
selected trial sites (approximately two in Germany and two in Poland; approximately 30 patients 
in total). 4.9 mL blood must be collected before morning dose and 15, 30, 60 and 120 minutes 
after morning dose at visit 2 (baseline, week 1) and at visit 5 (EoT, week 12). In total 49.0 mL 
blood will be collected per patient. 
The date and time of the last application of IMP prior to the PK sample be taken and the date and 
time of the PK sample must be documented in the eCRF.  
Collection, handling and shipment instructions for PK samples will be provided in a separate 
laboratory manual. 
Samples will be analyzed at: 
  
 
 
 
  
 
 
 
  
CCI, PPD

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5.5.1.6 
Diary 
The diaries will include instructions on the use of the IMP. Patients will be instructed to complete 
the diary after intake of each IMP dose. Date/time of intake of IMP will be recorded twice daily.  
At each visit at the site, the number of dose recorded on the diary will be reviewed and transcribed 
to the eCRF. Diary cards will be retained by trial sites as part of the source documentation and 
new diary cards will be dispensed. 
At subsequent visits, trial personnel will review, collect and dispense a new diary and determine 
whether the patient requires counseling for dosage compliance. In addition, each patient will be 
reminded to return completed diary at the next visit. 
5.5.2 Measurement of safety parameters 
Relevant medical history of the past five years and adverse events will be recorded.  
The following laboratory parameters will be collected at every visit (except serology): 
 
Table 4: Laboratory Parameter per visit: 
Parameter 
Screening 
Day 1 
Day 28 / 
56 
Day 84 
(EoT) 
Day 112 
(FU) 
Serology 
Hepatitis A IgG-antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis A IgM-antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis B core antibody-test  
X 
-- 
-- 
-- 
-- 
Hepatitis B surface antibody-test 
X 
-- 
-- 
-- 
-- 
Hepatitis B surface antigen-test 
X 
-- 
-- 
-- 
-- 
Hepatitis C virus antibody-test 
X 
-- 
-- 
-- 
-- 
HIV-1 antibody-test 
X 
-- 
-- 
-- 
-- 
HIV-2 antibody-test 
X 
-- 
-- 
-- 
-- 
Hematology 
RBC 
X 
X 
X 
X 
X 
WBC* including differential 
X 
X 
X 
X 
X 
Hemoglobin 
X 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
X 
MCH 
X 
X 
X 
X 
X 
MCV 
X 
X 
X 
X 
X 
MCHC 
X 
X 
X 
X 
X 
Platelets 
X 
X 
X 
X 
X 
Clinical Chemistry 
AST (GOT) 
X 
X 
X 
X 
X 

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Parameter 
Screening 
Day 1 
Day 28 / 
56 
Day 84 
(EoT) 
Day 112 
(FU) 
ALT (GPT) 
X 
X 
X 
X 
X 
GT 
X 
X 
X 
X 
X 
AP 
X 
X 
X 
X 
X 
Creatinine 
X 
X 
X 
X 
X 
Total bilirubin 
X 
X 
X 
X 
X 
CRP 
X 
X 
X 
X 
X 
hCG serum 
X 
-- 
-- 
-- 
-- 
Urine 
Urine dip stick test** 
X 
X 
X 
X 
X 
* including lymphocyte, neutrophils count, and eosinophils 
** leukocytes, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood/hemoglobin 
 
Hematological status, serology and clinical chemical parameters will be determined by LKF, Lise-
Meitner-Str. 25 – 29, 24223 Schwentinental, Germany. Urinalyses will be performed at the sites 
using a dipstick test (Medi-Test®, Combi 10L, Macherey-Nagel, Dueren, Germany). 
Approximately 19.2 ml of blood will be withdrawn at each visit with laboratory analysis (in total 
approximately 116 mL per patient). For the PK subgroup additional 24.5 mL will be withdrawn on 
day 1 and day 84 (in total 49 mL per patient). 
Spontaneously noted complaints will be recorded with duration, intensity and probability of a 
correlation with the IMP (see section 7.3., evaluation of adverse events). 
5.5.3 Vital signs 
Blood pressure and pulse rate will be measured at all visits after at least 5 minutes in a seated 
position. The following ranges for vital signs are given in table 5.  
Table 5: Vital signs ranges 
Variable 
Units 
Acceptable limit 
Systolic blood pressure 
mm Hg 
80 - 150 
Diastolic blood pressure 
mm Hg 
60 - 95 
Heart rate 
beats/min 
50 – 100 
Values outside 160 mm Hg / 95 mm Hg will not be randomized. 
5.5.4 Smoking and alcohol consumption  
Information on smoking and alcohol consumption will be documented at screening. 

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5.5.5 Physical examination 
The physical examination comprises a routine medical examination including gross neurological 
assessments. The following body systems will be examined: basic status of the main organ 
systems (ENT, heart, lungs, abdomen, neurological status) as well as physical examination of the 
skin. 
5.5.6 Appropriateness of assessments 
PASI, PGA, BSA are widely used, non-invasive methods for examining overall psoriasis severity 
and coverage. 
These methods are described in the EMA guideline [2] for evaluation of product efficacy. 
Assessments should be conducted by investigators who are experienced and have been trained 
on the use of these evaluation tools. If possible, the same investigator should complete the 
evaluations for a given patient throughout the trial. 
5.5.7 Primary efficacy/tolerability variable(s) 
Primary variable: 
The primary efficacy variables are: 
1. 75% improvement (response) in their PASI score (PASI 75) and  
2. Improvement (1 or more points on a 7 point scale) in their PGA score 
The secondary efficacy variables are: 
1. 50% improvement (response) in their PASI score (PASI 50)  
2. Mean PASI score and change to baseline  
3. Time to achieve PASI 50 and PASI 75 
4. Mean score and change from baseline in the PGA 
5. Mean score and change from baseline in the BSA 
6. PK data  
The 
primary 
variables 
are 
choose 
in 
accordance 
to 
the 
EMA 
guideline 
http://www.ema.europa.eu/docs/en GB/document library/Scientific guideline/2009/09/WC5000
03329.pdf (4)  

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6. 
Data analysis and statistics 
The statistical evaluation will be performed at bioskin using the software program SAS® (Statistical 
Analysis System, SAS, Cary, NC), Version 9.3 or higher.  
A formal statistical analysis plan (SAP), providing a complete description of the methodology of 
the planned statistical analyses, will be written, finalized, and signed prior to breaking the trial 
blind. Any changes in the statistical methods described in this protocol that occur prior to database 
lock will be documented in the SAP and will not require a protocol amendment.  
6.1 
Generation of data base 
In general, data from the source documents will be captured in an eCRF by a software package 
that can be customized for remote data entry procedure and that maintains an electronic audit 
trail. The eCRFs will be developed in the EDC system in accordance with bioskin SOPs under 
supervision and in agreement with the sponsor. The database structure will be validated.  
Only authorized site personnel will be able to enter/modify/correct data to the eCRF. The 
investigator/coordinator or designee must enter the information required by the protocol as soon 
as possible after the visit into the eCRF.  
The data will be checked for consistency. Queries for discrepant data may be generated 
automatically by the system upon entry or generated manually by the monitor or the trial data 
manager. All queries, whether generated by the system or by a user, will be in an electronic 
format. Once all the queries are closed and data have been verified by the CRA, the eCRF will 
be signed (eSignature) by the investigator and the database will be locked.  
All data management procedures will be detailed in a separate, specifically identified file that 
collectively will be referenced as the (DMP). 
Adverse events and medical history will be coded with Medical Dictionary for Regulatory Activities 
(MedDRA) mapping system, previous and concomitant therapy will be coded according to WHO-
DD. 
Patient data in PDF files generated from the eCRF will be provided to the site at the end of the 
trial. 
6.2 
Analysis sets and type of analysis 
The safety-evaluation-set (SES) will include all patients who received any trial medication at least 
once; all safety analyses will be based on the SES. 

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The full-analysis-set (FAS) will include all randomized patient who received at least one dose of 
IMP, and had at least one post-baseline assessment. The intention-to-treat (ITT) analysis will be 
based on the FAS. 
The valid-cases-set (VCS) will include all patient from the FAS, without any protocol violation 
interfering with the trial aims and with sufficient exposure to IMP. The per-protocol (PP) analysis 
will be based on the VCS.  
6.3 
Hypotheses 
Since this is an exploratory trial no formal hypotheses are postulated. The data will be evaluated 
descriptively. 
6.4 
Rationale for the sample size 
It is planned to recruit approximately 150 patients for this clinical trial in Germany and Poland 
(each country approximately 75 patients) to achieve 120 evaluable patients.  
No formal sample size calculations were performed for this explorative trial. A sample size of 40 
in each group is adequate to detect a difference in rates of at least 0,274, with 80% power, using 
a two group ﬡ2 test with a 0,100 two-sided significance level. 
6.5 
Statistical methods 
Statistical analyses will be performed using two-sided tests, without adjustment for multiplicity. All 
p-values will be interpreted descriptively.  
Data will be summarized by treatment group (and by visit when applicable), with respect to 
demographic and baseline characteristics, efficacy variables, and safety variables. 
Summary statistics will include the mean, number of non-missing cases (n), standard deviation, 
median, minimum, and maximum values for continuous variables, and frequencies and 
percentages for categorical variables. 
Categorical efficacy variables will be analyzed using the Cochran-Mantel-Haenszel (CMH) test 
with stratification by (pooled) analysis center and the Fisher’s exact test in case of analyses 
without stratification (mainly for safety assessment). 
Selected scores will be analyzed using an analysis of covariance (ANCOVA) model, with 
treatment group and (pooled) analysis center as factors and baseline outcome as covariate.  

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Time to event data will be analyzed using the Kaplan-Meier method, and treatment group 
differences will be tested by the log-rank test.  
Unless otherwise specified, baseline is defined as the latest non-missing observation prior to first 
treatment with IMP. 
Details of the model and the analyses will be specified in the SAP.  
6.5.1. Efficacy analyses 
Primary efficacy endpoints 
The comparisons of the treatment groups MP1032 300 mg bid and MP1032 150 mg bid, each vs. 
the placebo treatment, with respect to each, the PASI 75 rate and PGA improvement rate, at 
Week 12 (Day 84) will be evaluated by the CMH test stratified by (pooled) analysis center. The 
common odds-ratio with 95% confidence interval will be provided. The homogeneity of the 
individual odds-ratios will be assessed by the Breslow-Day test.  
Secondary efficacy endpoints 
Secondary efficacy endpoints will be evaluated descriptively. The methodology outlined in section 
6.5 will be applied for pairwise treatment comparisons vs. placebo.  
Responder rates will be evaluated as the primary efficacy endpoint.  
The change in the PASI score from baseline to each post baseline visit, respectively, will be 
evaluated using an analysis of covariance (ANCOVA) model, with treatment group and (pooled) 
analysis center as factors and baseline outcome as covariate.  
The time to achievement of PASI 50 and PASI 75, respectively, will be evaluated using the 
Kaplan-Meier method. Pairwise treatment group differences will be tested by the log-rank test. 
Descriptive summaries will be provided for each parameter by treatment group and by visit, if 
applicable. Percentages will be provided based on the number of non-missing cases, if not 
otherwise stated.  
6.5.2. Safety analyses 
All AEs reported during the trial will be listed, documenting course, severity, investigator 
assessment of the relationship to the IMPs, and outcome. AEs will be coded using the MedDRA 
mapping system for preferred terms (PTs) and system organ class (SOC).  

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Treatment-emergent adverse events (TEAEs), i.e. AEs with an onset or worsening on or after the 
time of the first IMP application will be summarized by the number of patients reporting TEAEs, 
primary system organ class (SOC), preferred term (PT), severity, and relationship to IMP.  
Listings of serious adverse events (SAE) and patients who prematurely discontinued treatment 
due to AEs will be given. 
Safety laboratory parameters (hematology, clinical chemistry) and vital signs will be summarized 
descriptively, including changes from baseline. Urinalysis outcomes will be summarized by 
frequency counts. 
6.5.3. Other analyses 
Blood MP1032 concentration-time data will be listed and displayed graphically, including the 
nominal and actual blood sampling time relative to the corresponding IMP administration time. 
Summary statistics of MP1032 levels by nominal sampling time will be provided. 
Statistical analyses will be performed using non-compartmental analysis (NCA) methods, as 
appropriate, providing Cmax, tmax and AUC(0,t). Listings and summary statistics of NCA parameters 
will be provided. 
6.6 
Handling of dropouts and missing data 
For the evaluation of success rates of the primary efficacy variables PASI and PGA missing PGA 
assessments and/or any parts of the PASI assessments will be evaluated as failure to achieve 
improvement. For descriptive analyses of PASI, PGA and BSA the last observation carried 
forward (LOCF) principle will be applied to impute the missing assessments, up to the Day 84 
visit. Follow-up assessments will not be imputed.  
Sensitivity of the primary efficacy analyses will be evaluated applying PP analyses.  
Handling of missing AE data, will be detailed in the SAP.  
6.7 
Identification of source data 
For the following source data should be available: 
 
patients identification incl. age, height and weight 
 
relevant previous and concomitant therapies  
 
up-to-date relevant medical history (last 5 years) 
 
findings at physical examination 
 
pregnancy test results 

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 
date of entry into the trial/visit dates 
 
vital signs 
 
adverse events  
 
laboratory results 
 
photographic documentation (at the selected sites) 
 
assessment scores PASI, PGA and BSA 
 
PK sampling (at the selected sites) 
 
Randomization number 
 
date and time of assessments  
 
IMP return / accountability and administration  
 
Missing treatment (diary) 
7. 
Adverse events 
7.1 
Evaluation of adverse events 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical trial subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. 
The period of observation for adverse events extends from the time the patient gives informed 
consent until the trial is completed. Adverse events that are still present after the last patient’s 
scheduled visit will be followed up 28 days of receiving the last IMP dose by means of a visit. 
After that time point the need for additional follow-up of ongoing AEs/SAEs will be discussed 
between the investigator and the sponsor, although in the event of discrepancies the investigator’s 
criteria will prevail. Adverse events occurring after the end of the clinical trial must be reported if 
the investigator considers there is a causal relationship with the investigational product. 
The investigator will be responsible for the necessary acute medical treatment of any adverse 
event required during the trial and will ensure that appropriate medical care will be maintained 
thereafter, if necessary. 
All patients experiencing adverse events - whether considered related with the use of the IMP or 
not - will be monitored until symptoms subside and any abnormal laboratory values have returned 
to baseline, or until there is a satisfactory explanation for the changes observed, or until death, in 
which case a full pathologist's report will be supplied, if possible. "Related" means a reasonable 

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possibility that the event may have been caused by the IMP. All findings will be reported on an 
"adverse event"/“serious adverse event“ page in the case report form. 
All adverse events, including intercurrent illnesses, will be reported and documented as described 
below. 
Adverse events are divided into the categories "serious" and "nonserious". This determines the 
procedure which will be used to report/document the adverse event (see below). 
Surgical procedures themselves are not adverse events; they are therapeutic measures for 
conditions that require surgery. The condition for which the surgery is required is an adverse 
event, if it occurs or is detected during the trial period. Planned surgical measures permitted by 
the clinical trial protocol and the condition(s) leading to these measures are not adverse events, 
if the condition(s) was (were) known before the start of treatment with investigational product. In 
the latter case the condition should be reported as medical history.  
7.2 
Definition of serious and nonserious adverse events 
A serious adverse event is any untoward medical occurrence that at any dose: 
• results in death or is life-threatening; 
• results in permanent or significant disability/incapacity; 
• requires inpatient hospitalization* or prolongation of hospitalization; 
• results in a congenital abnormality/birth defect. 
 
Medical and scientific judgment will be exercised in classification of other important medical 
events that may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the patient or may require intervention to prevent one of the other outcomes listed in 
the definition above. These should also usually be considered serious. 
Adverse events which do not fall into these categories are defined as nonserious. 
*Hospitalization solely for the purpose of diagnostic tests, even if related to an adverse event, 
elective hospitalization for an intervention which was already planned before the inclusion of the 
patient in the clinical trial, and admission to a day-care facility may not themselves constitute 
sufficient grounds to be considered as a serious adverse event.  

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7.3 
Reporting/documentation of adverse events 
7.3.1 Reporting of adverse events 
Adverse events either reported by the patient, or observed by the investigator must be recorded 
on the adverse event page of the eCRF and should be described in the following manner: 
The nature of the event will be described in precise, standard medical terminology (i.e. not 
necessarily the exact words used by the patient). If known, a specific diagnosis should be stated 
(e.g., allergic contact dermatitis). 
The intensity of the adverse event will be described in terms of mild, moderate or severe 
according to the investigator’s clinical judgment. 
• 
Mild: The adverse event does not interfere in a significant manner with the patient’s normal 
functioning level, but may be an annoyance.  
• 
Moderate: The adverse event produces some impairment of functioning but is not 
hazardous to health, but is uncomfortable and/or an embarrassment.  
• 
Severe: The adverse event produces significant impairment of functioning or 
incapacitation and is a hazard to the patient.  
The duration of the event will be described by the start date and end date. 
The causal relationship of the event to use of the IMP will be described in terms of: 
Certain: the adverse event 
• occurs in a plausible time relationship to IMP administration, and cannot be explained by 
concurrent disease or other drugs or chemicals, and 
•  follows a clinically plausible response to withdrawal of the IMP, and 
•   is definitive based on recognized pharmacological or other parameter associated with the IMP, 
and 
•   is confirmed by rechallenge procedure, if performed.  
Probable: the adverse event 
•  follows a reasonable temporal sequence from administration of the IMP, and 
•  is unlikely to be attributed to a disease or other drug/s, and 
•  disappears or decreases on withdrawal of the IMP 
 

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Possible: the adverse event 
•  follows a reasonable temporal sequence from administration of the IMP, but 
•  can also be explained by disease or other drugs, and 
•  information on drug withdrawal may be lacking or unclear.  
Unlikely: the adverse event 
•  does not follow a reasonable temporal sequence from administration of the IMP, and 
•  can be reasonably explained by disease or other drug/s, and 
•  does not follow a known pattern of response to the IMP, and 
•  does not reappear or worsen upon re-challenge, if performed.  
Not related: the adverse event 
• The event is either a pre-dose event or is definitely due to causes separate from the 
administration of the IMP, i.e. 
- documented pre-existing condition 
- technical and manual procedural problems 
- concomitant medication 
- patient’s clinical state 
The outcome of the event will be described in terms of: 
•  Recovered/resolved 
•  Recovering/resolving 
•  Recovered/resolved with sequelae 
•  Not recovered/not resolved 
•  Fatal 
•  Unknown 
It will also be recorded if the IMP use is continued, interrupted or discontinued. 
Note: Insofar as possible all serious adverse events should be followed-up to determine the final 
outcome of the event. Details of follow-up should be given (e.g. discontinuation of IMP, if specific 
treatment is required, if hospitalization is required, FU by PharmaLex, FU by Investigator etc.). 

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For the purpose of expedited reporting for the causality assessment (i.e. relationship of the 
adverse event to IMP) the terms “probable” and “possible” describe a relationship to IMP 
treatment, whereas the terms “unlikely” and “not related” classify the event as being not related 
to IMP treatment. 
7.3.2 Reporting of serious adverse events  
The investigator shall report all serious adverse events immediately (within 24 hours after he 
becomes aware of the event) by fax or e-mail to PharmaLex. General information on the patient 
(pseudonymed), the randomization number, and screening identification number event term 
(diagnosis) and measures already taken are to be reported. The immediate report shall be 
followed by detailed, written reports. The investigator is obliged to completely document the 
course of the event and the measures taken, if possible including the original findings and using 
the form for serious adverse events. Additional documentation is carried out on the case report 
forms. 
SAE reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
 
 
For reported deaths of a patient, the investigator shall supply the sponsor and the ethics 
committee with any additional information requested. 
The sponsor/PharmaLex shall ensure that all relevant information about suspected unexpected 
serious adverse reactions (SUSAR) that are fatal or life-threatening is recorded and reported as 
soon as possible to the competent authorities in all the member states concerned, and to the 
ethics committee, and in any case no later than seven days after knowledge by the sponsor of 
such a case, and that relevant follow-up information is subsequently communicated within an 
additional eight days.  
All other SUSARs shall be reported to the competent authorities concerned and to the ethics 
committee concerned as soon as possible but within a maximum of fifteen days of first knowledge 
by the sponsor accordingly.  
PharmaLex shall also inform all investigators.  
CCI, PPD

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7.4 
Pregnancies  
Pregnancies occurring during a patient's participation in a clinical trial, although not 
typically considered an SAE, must be notified to the sponsor within the same timelines as an 
SAE (within 24 hours after being made aware of the pregnancy) on a pregnancy notification form. 
The pregnant trial patient should be withdrawn immediately from the trial. 
Pregnancy reports should be emailed/faxed to the Pharmacovigilance unit of the PV vendor: 
 
 
 
 
 
 
 
Any pregnancy occurring in the trial should be followed up until outcome. If relevant, the 
development of the newborn has to be monitored for an appropriate time post-delivery. 
8. 
Case report form (CRF), documentation and archiving 
•  The CRFs will be drawn up by bioskin in agreement with the sponsor. 
•  All trial documents, in particular the eCRFs, must be continually filled out. The eCRF is validated  
   system which automatically creates an audit trail for all changes. 
•  The documentation will be kept in such a way, that it is possible to easily reconstruct the course  
   of the trial at a later date (in accordance with the details given in the clinical trial protocol). All  
   documents will be filed in the TMF or the investigator file, respectively. 
•  Following the specific patient information, consent forms will be signed by the patient and the  
   physician responsible for supplying information twice. One will be filed in the investigator file.  
   And one will be given to the patient. 
•  Electronic data media are to be clearly marked with the trial number/data type/date/hard- and   
   software information (readability). 
•  All trial documents drawn up or available in paper form (e.g. raw data on data forms, CRFs, 
   informal papers, printouts, etc.) are to be uniformly labeled with the trial number/screening 
  number/data type/measurement time point and/or time/date/initials of the staff member. 
•  Clinical research associate (CRA) will verify all data entered into eCRFs for completeness   
   and accuracy with reference to the source documents and records and will issue manual  
CCI, PPD

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   data queries to correct missing data or discrepancies found against the source within the  
   EDC system. 
•  Data validation will consist of automated and manual edit checks that are created directly  
   in EDC. Automated edit checks will be executed on all data points defined and documented    
   by the trial team and data management. 
•  Any changes from the clinical trial protocol in trial planning or execution after submission of the 
   final version of the clinical trial protocol that have ethical or medical implications are to be  
   documented as a „Substantial amendment to clinical trial protocol,“ including cause, content, 
   grounds, consequences, date and the signature of the sponsor and investigator. Such an  
   amendment must be submitted to the appropriate ethics committee(s)/competent authority(ies)  
   for approval. All staff involved in the trial will be informed by the clinical trial manager and  
   investigator. Changes in the clinical trial protocol are only allowed after prior consultation with  
   the person in charge of the trial at the sponsor (clinical trial manager). Changes without ethical  
   or medical implications are to be documented as non-substantial amendments or file notes  
    including date and signature of the sponsor and the responsible person at bioskin. 
•  After all data have been verified by the CRA, an investigator or sub-investigator is required to  
   review and approve all eCRFs prior to database lock and breaking of the blind. 
•  After database lock, each site will be provided with the eCRF data from their site for local 
   archival purposes. 
•  After the conclusion of the trial, the original trial documents (TMF, CRFs) are to be submitted  
   to the sponsor according to the agreements made. 
•  Currently the statutory period for archiving the documents after conclusion of the trial is at least 
   15 years. 
8.1 
Primary source documents 
The investigator must maintain primary source documents supporting significant data for each 
patient’s medical notes.  
All applicable trial data collected on each patient will be recorded by trained site personnel into 
the source data record and the eCRF. Only authorized site personnel will be able to 
enter/modify/correct data to the eCRF. 
Source documents such as the medical records are to be maintained separately from the eCRF 
to allow data verification. Because of the potential for errors, inaccuracies, and illegibility in 
transcribing data onto eCRFs, originals of laboratory and other test results must be kept on file 

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with the patient’s source documentation. The investigator must also retain all patient-specific 
printouts/reports of tests and procedures performed as a requirement of the trial. During 
monitoring visits the monitor will validate eCRF entries against these sources of data. 
eCRFs, source documents, and copies of test results must be available at all times for inspection 
by the trial monitor, auditors, or regulatory inspectors. The following should also be available for 
review 
 
Patient screening log, which should reflect the reason any patient screened for the trial 
was found to be ineligible; 
 
Site personnel and delegation log, which will list all site personnel with their responsibilities 
as delegated by the investigator and their signatures. This log will be maintained at the 
site throughout the trial; 
 
Monitoring visit log, which will list the date and purpose of all monitoring visits by the 
sponsor or designee; 
 
Enrollment log, which will list patient initials and start and end dates for all enrolled 
patients; 
 
Drug inventory/Packing slip, which will list the total amount of drug shipped to the site and 
received and signed for by the investigator; 
 
IMP dispensing log, which will list the total amount of IMP dispensed to and returned by 
each patient; 
 
ICF which must be available for each patient and be verified for proper documentation. 
Following the specific patient information, consent forms will be signed by the patient and 
the physician responsible for supplying information twice. One will be filed in the 
investigator file.  And one will be given to the patient; 
 
All correspondence. 
9. 
Statutory regulations and GCP 
This clinical trial will be conducted in compliance with the protocol. Planning and execution of this 
clinical trial are subject to globally accepted standards of good clinical practice (as defined in the 
ICH E6 (R2) guideline for good clinical practice, November 2016), in agreement with the 
Declaration of Helsinki and in keeping with local regulations. 

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9.1 
Ethics committee/competent authorities 
Before the start of the trial, the clinical trial protocol, informed consent document, and other 
appropriate documents will be submitted to the appropriate ethics committees (ECs) and 
competent authorities (CAs). The trial must not start before approval has been granted by the 
appropriate EC and no grounds for non-acceptance have been issued by the CA concerned.  
9.2 
Insurance 
Insurance policy will be provided for each country participating in the study in accordance with 
local regulations.  
In Germany every patient participating in the clinical trial will be insured in accordance with § 40 
paragraph 3 of the German drug law against injuries to health which may occur during the trial. 
Excluded from this however are injuries to health and deteriorations of illnesses already in 
existence which would have occurred or continued to exist even if the patient had not taken part 
in the clinical trial. 
The insurance cover is jeopardized if the patient fails to report immediately to the investigator or 
responsible physician any injury to health which might have resulted from participation in the 
clinical trial, or if he/she undergoes any other medical treatment without their consent before the 
clinical trial has been completely finished - insofar as the individual patient is concerned. 
Any injury to health which might have occurred as a result of participation in the clinical trial must 
be reported by the patient to the insurer without delay. The investigator is obliged to make such 
a report in any case. 
The patient insurance will be arranged by bioskin GmbH on the basis of the final version of the 
patient information and informed consent form. The patient insurer is 
 
. 
The insurance policy number is 
.  
9.3 
Patient instruction and consent forms 
Every patient will receive a complete and comprehensive explanation of the significance, nature, 
extent and possible risks of the trial. To this end a detailed, written patient information sheet will 
be made available. In addition a physician will carry out an oral information session during which 
the patients will be given sufficient time and opportunity to clarify remaining questions. Two 
identical forms for written informed consent will be given to the patients for signature. One copy 
of the signed forms will be archived in the investigator file and the other retained by the patient. 
CCI
CCI

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The investigator will acknowledge instruction of every patient in accordance with the clinical trial 
protocol and the existence of a signed consent form. 
9.4 
Data protection 
During the clinical trial medical and personal information (like age, gender, racial, and ethnic 
origin) will be collected at the site and documented in the personal file or electronically saved. In 
addition, important data for the clinical trial (including photos and PK data of the subgroups) will 
be saved pseudonymized, transferred, and evaluated. 
If necessary, the collected and saved data (including the photos and PK data) during the clinical 
trial will be held for inspection by the supervisory authority or by people charged by the sponsor 
who check that the trial is done properly. If needed, the related data will be shared pseudonymized 
to: 
 
The sponsor or sponsor-appointed party for the purpose of scientific analysis; 
 
The applicant and the authority responsible for marketing authorization, in case that 
application for marketing authorization is requested; 
 
Sponsor and the responsible competent authority, which will also forward the data to the 
European database, in case of adverse events of the trial drug; 
 
Parties in Europe and in non-European foreign countries which are affiliates of the 
Sponsor and as well forwarded to the responsible authorities in charge of marketing 
authorization by the latter. 
 
Personal and medical data collected during the trial may be moved, stored and used in the EU or 
another country where the sponsor or those working with the sponsor located. Data – including 
trial results – might be published in Scientific Journals, Conference abstract, etc. The trial and 
trial data will be published in clinicaltrials.gov. 
9.5 
Termination of participation 
Every patient has the right to refuse further participation in the trial at any point in time and without 
giving reasons. Nonetheless, efforts should be made to find out the cause and to document it on 
the case report form. If the administration of the investigational product has already taken place 
at the time of refusal, the patient should be convinced to consent to a complete final examination 
as planned in the protocol in his/her own interest. This has to be documented on the 
corresponding pages of the eCRF.  

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9.6 
Quality control (Trial monitoring) 
According to bioskin quality management procedures internal quality control will be applied to all 
steps of the trial e.g. planning, conduct, analysis and reporting.  
A representative of sponsor or bioskin will monitor the trial progress as regularly as necessary 
during the conduct of the trial until the last case report forms have been completed and all queries 
have been resolved.  
The trial and site activities will be monitored according to the ICH-GCP guidelines for: 
 
Protocol adherence (trial is conducted in accordance with the currently approved 
protocol and any other trial agreements) 
 
Quality of data (data are authentic, accurate, and complete) 
 
Drug accountability 
 
Protection of safety and rights of patients 
 
Compliance with regulatory requirements (trial is conducted in accordance with GCP, 
and all applicable regulatory requirements) 
 
Adequacy of the facilities (unchanged high qualification of the site and site staff)  
The investigators and the head of the medical institutions (where applicable) agree to allow the 
monitor direct access to all relevant documents. 
9.7 
Quality assurance 
To ensure compliance with GCP and all applicable regulatory requirements Sponsor may conduct 
a quality assurance assessment and/or audit of the site records at any time during or after 
completion of the trial. 
Auditing will be performed by or on behalf of Quality Assurance MetrioPharm in accordance with 
the requirements of Note for Guidance on Good Clinical Practice, the clinical trial protocol, 
applicable standard operating procedures and according to the agreed audit plan. 
All audit activities in the course of MP1032-CT04 will be documented and archived. 
Independent of any sponsor audit the regulatory agencies may conduct a regulatory inspection at 
any time during or after completion of the trial. 
In the event of an assessment, audit or inspection, the investigators (and institutions) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and to 
allocate their time and the time of their staff to discuss the conduct of the trial, any findings/relevant 
issues and to implement any corrective and/or preventative actions to address any findings/issues 
identified. 

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9.8 
Handling of investigational medicinal products 
The investigator or his representative confirms receipt of the IMPs in writing and will only use 
them within the framework of this clinical trial and in accordance with the existing clinical trial 
protocol. All containers opened, together with remaining contents and unopened containers will 
be returned to the manufacturer at the end of the trial.  
Delivery, consumption and return must be completely documented.  
A written explanation must be compiled on any containers/investigational products which are 
missing. The investigational products will be stored in a safe place according to the 
manufacturer’s instructions for storage. 
The investigator is responsible for ensuring appropriate storage and control of the IMPs. Storage 
records, including temperature records should be maintained and be available for inspection 
during the course of the trial.  
Deviations in storage requirements should be reported to the CRA, the bioskin CTM and to the 
sponsor and may require that the IMP is quarantined during the review of the deviation. 

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11. 
Literature 
 
[1] 
Nast A. Boehncke WH. Mrowietz U et al. S3-Leitlinie zur Therapie der Psoriasis vulgaris 
Update 2011. JDDG; 2011; 9 (Suppl. 2):S1-S104. 
[2]  
EMA Guideline on Psoriasis. Guideline on Clinical Investigation of Medicinal Products 
Indicated for the Treatment of Psoriasis. Issued by the European Medicines Agency, 
London,18 November 2004. Accessed 27 Jan 2016. 
[3] 
MetrioPharmAG. Investigator’s Brochure MP1032. Edition No. 5. 18. Sep 2017. 
[4] 
World Health Association Declaration of Helsinki. Ethical Principles for Medical Research 
involving Human Patients. Adopted by the 18th WMA General Assembly, Helsinki, 
Finland, June 1964, and amended by the 48th WMA General Assembly, Somerset West, 
Republic of South Africa, October 1996. 
[5] 
Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95). The European Agency 
for the Evaluation of Medicinal Products (EMEA) 2002;1-59. 
[6] 
Grekin SJ, Ellis CN. Evaluating the severity of dermatologic disorders. Dermatol Ther 
2009;22(3);191-198. 

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              documentation will be performed prior to the first administration of IMP 
d) 
Only performed in a subgroup of approx. 4 sites (approx. 30 patients); on Day 1 and Day 84 first PK  
sample will be performed prior to the first administration of IMP. PK samples will be collected before IMP 
administration, and 15, 30, 60 and 120 minutes after administration of IMP. 
e) 
IMP administration will start on Day 1 after randomization and will continue as self- 
administration by trial patients at home until Day 84. Patients included in the PK analysis will administrate 
the first treatment (Day 1) at the site. All patients will administrate the last treatment (Day 84) at the sites. 
f) 
AE reporting starts after the signature of informed consent form and finishes at the End of Study Follow-Up  
Visit. 
 
 
 
 
 
 
 
 
 
 

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Appendix B Psoriasis Area Severity Index (PASI) 
 
Shown below is the original description of the PASI (Fredriksson T, Pettersson U. 
Dermatologica 1978;157:238-44) which involves the assessment of erythema (E), 
infiltration (I), and desquamation (D), and body surface area involvement (A) over 4 
body regions (head (h), trunk (t), upper (u) and lower (l) extremities). 
Degree of severity (per body region) 
Value given 
No symptoms 
0 
Slight 
1 
Moderate 
2 
Marked 
3 
Very marked 
4 
 
Surface involved (per body region) 
Value given 
<10% 
1 
10-29% 
2 
30-49% 
3 
50-69% 
4 
70-89% 
5 
90-100% 
6 
 
Because the head, upper extremities, trunk, and lower extremities correspond to 
approximately 10, 20, 30, and 40% of body surface area, respectively, the PASI score is 
calculated by the formula: 
PASI  =  0.1(Eh + Ih +Dh)Ah + 0.2(Eu + Iu + Du)Au + 0.3(Et + It + Dt)At + 0.4(El +Il 
+Dl)Al