A Randomized, Subject and Investigator Blinded, Placebo-controlled, Multi-center Study in Parallel Groups to Assess the Efficacy and Safety of CJM112 in Patients With Moderate to Severe Inflammatory Acne
Phase: PHASE2
Conditions: Acne Vulgaris
Sponsor: Novartis Pharmaceuticals

Novartis Institutes for BioMedical Research
CJM112
Clinical Trial Protocol CCJM112X2203
A randomized, subject and investigator blinded, 
placebo-controlled, multi-center study in parallel groups 
to assess the efficacy and safety of CJM112 in patients 
with moderate to severe inflammatory acne
Document type:
Amended Protocol Version
EUDRACT number:
2016-002492-95
Version number:
v02 (Clean)
Clinical Trial Phase:
II
Release date:
14-Dec-2016
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis

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Site Operations Manual (SOM)
A Site Operations Manual (SOM) accompanies this protocol, providing the operational details 
for study conduct. Note: The SOM will not be part of the Clinical Study Report.
Notification of serious adverse events
Dear Investigator,
You must report a Serious Adverse Event (SAE) (initial or follow-up) to Novartis as 
summarized below.  Refer to Section 9.2 of the protocol for SAE criteria and additional 
requirements.  See also page 2 of the SOM for further details on the method of reporting a SAE.

Complete SAE report

Submit SAE report to Novartis Drug Safety and Epidemiology (DS&E) within 24 hours 
after awareness of the SAE

Notify the Novartis Medical Lead

The fax number(s) and email address(es) are located in the SOM. 

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Table of contents
Site Operations Manual (SOM)...........................................................................................2
Notification of serious adverse events.................................................................................2
Table of contents .................................................................................................................3
List of tables ........................................................................................................................7
List of figures ......................................................................................................................7
List of abbreviations............................................................................................................8
Pharmacokinetic definitions and symbols.........................................................................12
Glossary of terms...............................................................................................................13
Protocol synopsis...............................................................................................................21
1
Introduction .......................................................................................................................25
1.1
Background............................................................................................................25
1.4
Study purpose ........................................................................................................31
2
Study objectives and endpoints .........................................................................................31
2.1
Primary objective...................................................................................................31
2.2
Secondary objective(s)...........................................................................................31
3
Investigational plan ...........................................................................................................33
3.1
Study design...........................................................................................................33
3.2
Rationale of study design.......................................................................................34
3.3
Rationale for dose/regimen, route of administration and duration of treatment....37
3.4
Rationale for choice of comparator .......................................................................38
3.5
Rationale for choice of background therapy..........................................................39
3.7
Risks and benefits..................................................................................................39
3.7.1
Blood sample volumes ..........................................................................41
4
Population..........................................................................................................................43
4.1
Inclusion criteria ....................................................................................................43
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4.2
Exclusion criteria...................................................................................................43
5
Restrictions for Study Subjects .........................................................................................46
5.1
Contraception requirements...................................................................................46
5.2
Prohibited treatment...............................................................................................47
5.3
Dietary restrictions and smoking...........................................................................48
5.4
Other restrictions ...................................................................................................48
6
Treatment...........................................................................................................................49
6.1
Study treatment......................................................................................................49
6.1.1
Investigational treatment and placebo...................................................49
6.1.2
Additional study treatment....................................................................49
6.2
Treatment arms ......................................................................................................49
6.3
Treatment assignment and randomization.............................................................50
6.4
Treatment blinding.................................................................................................51
6.5
Treating the subject................................................................................................52
6.6
Permitted dose adjustments and interruptions of study treatment.........................52
6.7
Emergency breaking of assigned treatment code ..................................................52
6.8
Treatment exposure and compliance .....................................................................53
6.9
Recommended treatment of adverse events ..........................................................53
6.10
Rescue medication.................................................................................................53
6.11
Concomitant treatment...........................................................................................53
7
Study completion and discontinuation ..............................................................................54
7.1
Study completion and post-study treatment ..........................................................54
7.2
Discontinuation of study treatment........................................................................54
7.3
Withdrawal of informed consent ...........................................................................55
7.4
Lost to follow-up ...................................................................................................55
7.5
Study stopping rules ..............................................................................................55
7.6
Early study termination by the sponsor .................................................................56
8
Procedures and assessments ..............................................................................................57
8.1
Informed consent procedures.................................................................................60
8.2
Subject screening...................................................................................................60
8.3
Subject demographics/other baseline characteristics.............................................61
8.4
Efficacy / Pharmacodynamics ...............................................................................61
8.4.1
Clinical Outcome Assessments (COAs) ...............................................61
8.5
Safety.....................................................................................................................67
8.5.1
Physical examination ............................................................................67
8.5.2
Vital signs..............................................................................................67
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8.5.3
Height and weight .................................................................................67
8.5.4
Laboratory evaluations..........................................................................68
8.5.5
Electrocardiogram (ECG) .....................................................................68
8.5.6
Pregnancy and assessments of fertility .................................................69
8.5.7
Tuberculosis test....................................................................................69
8.5.8
Immunogenicity (anti-CJM112 antibodies) ..........................................69
8.6
Pharmacokinetics...................................................................................................69
9
Safety monitoring ..............................................................................................................71
9.1
Adverse events.......................................................................................................71
9.2
Serious adverse event reporting.............................................................................72
9.2.1
Definition of SAE .................................................................................72
9.2.2
SAE reporting........................................................................................73
9.3
Liver safety monitoring .........................................................................................74
9.4
Renal safety monitoring.........................................................................................75
9.5
Reporting Medication errors including misuse/abuse ...........................................75
9.6
Pregnancy reporting...............................................................................................76
9.7
Early phase safety monitoring ...............................................................................76
10 Data review and database management.............................................................................77
10.1
Site monitoring ......................................................................................................77
10.2
Data collection.......................................................................................................77
10.3
Database management and quality control............................................................78
10.4
Data Monitoring Committee..................................................................................79
10.5
Adjudication Committee........................................................................................79
11 Data analysis......................................................................................................................79
11.1
Analysis sets ..........................................................................................................79
11.2
Subject demographics and other baseline characteristics......................................79
11.3
Treatments .............................................................................................................79
11.4
Analysis of the primary variable(s) .......................................................................80
11.4.1
Variable(s).............................................................................................80
11.4.2
Statistical model, hypothesis, and method of analysis..........................80
11.4.3
Handling of missing values/censoring/discontinuations.......................81
11.4.4
Sensitivity analyses ...............................................................................81
11.5
Analysis of secondary variable(s)..........................................................................81
11.5.1
Safety.....................................................................................................81
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11.5.2
Pharmacokinetics ..................................................................................82
11.5.3
Pharmacokinetic / pharmacodynamic interactions................................82
11.7
Sample size calculation..........................................................................................84
11.8
Power for analysis of key secondary variables......................................................85
12 Ethical considerations........................................................................................................87
12.1
Regulatory and ethical compliance........................................................................87
12.2
Responsibilities of the investigator and IRB/IEC..................................................87
12.3
Publication of study protocol and results...............................................................87
13 Protocol adherence ............................................................................................................87
13.1
Protocol Amendments ...........................................................................................88
14 References .........................................................................................................................89
15 Appendix 1: Liver Event Definitions and Follow-up Requirements.................................91
16 Appendix 2: Specific Renal Alert Criteria and Actions ....................................................93
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Table 5-1
Prohibited treatment..............................................................................47
Table 6-1
Overview of Investigational treatment..................................................49
Table 6-2
Blinding levels ......................................................................................52
Table 8-1
Assessment Schedule ............................................................................57
Table 8-2
Assessment for facial inflammatory acne (IGA) Grade........................63
Table 8-3
Comprehensive Acne severity scale for non-facial acne (CASS).........63
Table 8-4
Patient Global Assessment....................................................................64
Table 9-1
Summary of reporting requirements for medication errors...................76
Table 11-1
Operating characteristics of decision rules for n=21 per arm ...............85
Table 15-1
Liver Event Definitions.........................................................................91
Table 15-2
Actions required for Liver Events.........................................................91
Table 15-3
Exclusion of underlying liver disease ...................................................92
Table 16-1
Specific Renal Alert Criteria and Actions.............................................93
Table 16-2
Follow-up of renal events......................................................................94
List of figures
Figure 3-1
Study design..........................................................................................34
Figure 11-1
Operating characteristics curve for n=21 per arm.................................85
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List of abbreviations
γ-GT
Gamma-Glutamyl transferase
ACR
Albumin-Creatinine Ratio 
ADA
Anti-Drug Antibody
ADR
Adverse Drug Reaction
AE
Adverse Event
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
BD-2
β-Defensin-2 
BM
Biomarker
BMI
Body Mass Index
CAH
Congenital adrenal hyperplasia
CASS
Comprehensive Acne Severity Scale
CDER
Center for Drug Evaluation and Research
CFR
Code of Federal Regulation
COA
Clinical Outcome Assessments
COAR
Clinical Operations, Analytics & Regions
CPK
Creatinine Phosphokinase
CRF
Case Report/Record Form (paper or electronic)
CRO
Contract Research Organization
CRP
C-reactive protein
CV
Coefficient of Variation
DAR
Dose Administration Record
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
DS&E
Drug Safety and Epidemiology
ECG
Electrocardiogram
EDC
Electronic Data Capture
ELISA
Enzyme-linked immunosorbent assay
EOS
End of Study
FDA
Food and Drug Administration

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FIH
First in Human
GCP
Good Clinical Practice
GEE
Generalized Estimating Equations
GLMM
Generalized Linear Mixed Model
h
hour
hCG
Human Chorionic Gonadotropin
H&E
Hemotoxyllin-Eosin
HIV
Human Immunodeficiency Virus
HS
Hidradenitis Suppurativa
IA
Interim Analysis
IB
Investigator’s Brochure
ICH
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IGA
Investigator Global Assessment
IgG
Immunoglobulin G
IHC
Immunohistochemistry
IL
Interleukin
IN
Investigator Notification
INR
International Normalized Ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology
IUD
Intrauterine device
IUS
Intrauterine system
i.v.
intravenous
LLOQ
Lower Limit of Quantification
LOCF
Last Observation Carried Forward
LTB4
Leukotriene B4
mAb
Mouse Antibody
MAR
Missing at Random
MedDRA
Medical Dictionary for Regulatory Activities
mg
milligram(s)

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mL
milliliter(s)
MMRM
Mixed effect Model for Repeated Measures
MPO
Myeloperoxidase
MRI
Magnetic Resonance Imaging
ng
nanogram
NIBR
Novartis Institute of Biomedical Research
NOAEL
no observed adverse effect level
NRS
Numerical rating scale
OTC
Over the counter
PAPA
Pyogenic arthritis pyoderma gangrenosum and acne
PASH
Pyoderma gangrenosum, acne, and suppurative hidradenitis 
PASI
Psoriasis Area Severity Index
PCR
Protein-Creatinine Ratio
PD
Pharmacodynamic(s)
PDT
Photodynamic Therapy
PK
pharmacokinetic(s)
POC
Proof of Concept
PRIDE
Papulopustules and/or paronychia, Regulatory abnormalities of hair growth, 
Itching, and Dryness due to Epidermal growth factor receptor inhibitors
PRO
Patient reported outcomes
PSTPIP1
Proline-Serine-Threonine Phosphatase Interacting Protein 1
PT/INR
Prothrombin Tine/ International Normalized Ratio
q4w
Every four weeks
SAD
Single Ascending Dose
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAPHO
Synovitis Acne Pustulosis Hyperostosis Osteitis
s.c.
Subcutaneous
sCR
serum Creatinine
SD
standard deviation
SER
Sebum Excretion Rate
SOC
Standard of Care 

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SOM
Site Operations Manual
SUSAR
Suspected Unexpected Serious Adverse Reactions
TBL
Total Bilirubin
ULN
Upper limit of normal
WHO
World Health Organization
WOCBP
Woman of Child Bearing Potential 

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Pharmacokinetic definitions and symbols
Cmin,ss
The lowest plasma (or serum or blood) concentration observed during a 
dosing interval at steady state [mass / volume]
Cmax,ss
The observed maximum serum concentration following drug administration 
at steady state [mass / volume]
Cav,ss
The average steady state serum concentration during multiple dosing
λz
The apparent volume of distribution during the terminal elimination phase
following extravascular administration [volume]
T1/2
The terminal elimination half-life [time]
AUCtau,ss
The area under the serum concentration-time curve from time zero to the end
of the dosing interval tau at steady state [mass x time / volume]

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Glossary of terms
Assessment
A procedure used to generate data required by the study
Cohort
A specific group of subjects fulfilling certain criteria
Control drug
Any drug (an active drug or an inactive drug, such as a placebo) 
which is used as a comparator to the investigational drug being 
tested in the trial
Dosage
Dose of the study treatment given to the subject in a time unit 
 
Enrollment
Point/time of subject entry into the study at which informed consent 
must be obtained (i.e. prior to starting any of the procedures 
described in the protocol)
Healthy volunteer
A person with no known significant health problems who 
volunteers to be a study participant 
Investigational drug
The study drug whose properties are being tested in the study; this 
definition is consistent with USA CFR 21 Section 312.3 and 
Directive 2001/20/EC and is synonymous with “investigational new 
drug” or “test substance”
Investigational 
treatment
All investigational drug(s) whose properties are being tested in the 
study as well as their associated treatment controls. This includes 
any placebos, any active controls, as well as approved drugs used 
outside of their indication/approved dosage or tested in a fixed 
combination. Investigational treatment generally does not include 
other treatments administered as concomitant background therapy 
required or allowed by the protocol when used within approved 
indication/dosage.
Medication number
A unique identifier on the label of each study drug package in 
studies that dispense study drug using an IRT system.
Medication pack 
number
A unique identifier on the label of each drug package in studies that 
dispense study treatment using an IRT system
Patient
An individual with the condition of interest
Period
A minor subdivision of the study timeline; divides phases into 
smaller functional segments such as screening, baseline, titration, 
washout, etc.
Premature subject 
withdrawal
Point/time when the subject exits from the study prior to the 
planned completion of all study drug administration and 
assessments; at this time all study drug administration is 
discontinued and no further assessments are planned.
Randomization number
A unique identifier assigned to each randomized subject, 
corresponding to a specific treatment arm assignment

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Screen Failure
A subject who is screened but is not treated or randomized
Stage
A major subdivision of the study timeline; begins and ends with 
major study milestones such as enrollment, randomization, 
completion of treatment, etc.
Study completion
Point/time at which the subject came in for a final evaluation visit 
or when study drug was discontinued whichever is later.
Study drug 
discontinuation
Point/time when subject permanently stops taking study drug for 
any reason; may or may not also be the point/time of premature 
subject withdrawal.
Study treatment
Any drug administered to the study participants as part of the 
required study procedures; includes investigational drug (s), 
control(s) or non-investigational medicinal product(s)
Study treatment 
discontinuation
When the subject permanently stops taking study treatment prior to 
the defined study treatment completion date
Subject
A trial participant (can be a healthy volunteer or a patient)
Subject number
A unique number assigned to each subject upon signing the 
informed consent. This number is the definitive, unique identifier 
for the subject and should be used to identify the subject throughout 
the study for all data collected, sample labels, etc.
Treatment number
A unique identifier assigned in non-randomized studies to each 
dosed subject, corresponding to a specific treatment arm 
Variable
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the drug 
being tested in the study
Withdrawal of consent 
(WoC)
Withdrawal of consent from the study is defined as when a subject 
does not want to participate in the study any longer, and does not 
want any further visits or assessments, and does not want any 
further study related contact, and does not allow analysis of already 
obtained biologic material

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C
 
 
C
 
 
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Protocol synopsis
Protocol 
number
CCJM112X2203
Title
A randomized, subject and investigator blinded, placebo-controlled, multi-center 
study in parallel groups to assess the efficacy and safety of CJM112 in patients 
with moderate to severe inflammatory acne
Brief title
Study of efficacy and safety of CJM112 in patients with moderate to severe 
inflammatory acne
Sponsor and 
Clinical Trial 
Phase
Novartis
Phase II
Intervention 
type
Biologic 
Study type
Interventional 
Purpose and 
rationale
The study is designed primarily to assess preliminary efficacy and safety of 
CJM112 in patients with moderate to severe inflammatory acne and to determine if 
CJM112 has an adequate clinical profile for further clinical development. 
In addition, sustainability of response and dose relationship will be explored.
Primary 
Objective
To assess the efficacy of CJM112 versus placebo on facial inflammatory lesion 
counts in patients with moderate to severe inflammatory acne.
Secondary 
Objectives
To assess the safety and tolerability of CJM112 in patients with moderate to severe 
inflammatory acne.
To assess the pharmacokinetics of CJM112 in patients with moderate to severe acne.
Study design
This is a randomized, placebo controlled, subject and investigator blinded, 
multicenter, non-confirmatory, parallel group, proof of concept study in patients 
with moderate to severe inflammatory acne. After an initial screening period (up to 
4 weeks), the study is conducted in 2 consecutive treatment periods, each of 12 
weeks, to show clinical efficacy in treatment period 1, and potential sustainability 
of response in extension period 2.  At the beginning of treatment period 1, patients 
are randomized to one of 3 treatment groups for the first 12 weeks only:
1
 CJM112 s.c. at monthly intervals
2
 CJM112 s.c.at monthly intervals
3 Placebo s.c. at monthly intervals 
At the end of treatment period 1, all patients will be offered the opportunity to remain in 
the study for extension period 2. Patients who enter extension period 2 will receive the 
following treatments: 

Treatment Period 1, 
 Extension Period 2, 

Treatment Period 1, 
 Extension Period 2, 

Treatment Period 1, Placebo. Extension Period 2, 
 via re-
randomization. 
Therefore, exposure to placebo will be limited to a maximum of 12 weeks (treatment 
period 1). 

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Population
The patients included in the study are patients with moderate to severe 
inflammatory acne who have previously failed other systemic therapies, and do not 
have more than 5 nodules to exclude severe cases of nodulocystic acne, often 
associated with a high potential for scarring.  A minimal count of 25 facial 
inflammatory lesions (papules, pustules, nodules) is needed for inclusion. 
Key Inclusion 
criteria

Written informed consent must be obtained before any assessment is 
performed.

Male and female subjects aged 18 to 45 years of age included and otherwise 
in good health as determined by medical history, physical examination, vital 
signs, ECGs and laboratory tests at screening.

Body weight between 50 and 120 kg, inclusive at screening.

Patients with papulo-pustular acne vulgaris having between 25 and 100 facial 
inflammatory lesions (papules, pustules and nodules), and presence of non-
inflammatory lesions (open and closed comedones) on the face at screening 
and baseline, who have failed systemic therapy for inflammatory acne.

No more than 5 facial inflammatory nodules at screening and baseline.

Investigator's Global assessment (IGA) score of at least moderate (3) acne 
severity at screening and baseline.

Able to communicate well with the investigator, to understand and comply with 
the requirements of the study.
Key Exclusion 
criteria

Use of investigational drugs at the time of screening, or within 4 weeks or 
5 half-lives of screening, whichever is longer; or longer if required by local 
regulations.

Use of any topical anti-acne prescription treatment within 2 weeks and 
any OTC anti-acne treatment within 1 week of baseline (use of medicated 
(anti-acne) creams, medicated cleansers or medicated soaps is prohibited for 
treatment period 1).

Use of any oral/systemic treatment for acne, including oral antibiotics, 
dapsone, within 4 weeks prior to baseline.

Use of systemic or lesional injected (for acne) corticosteroids or systemic 
immunomodulators (such as cyclosporine, methotrexate, azathioprine, etc.) 
within 4 weeks before baseline (see Section 5.2).

Use of any systemic hormonal treatment (in particular anti-androgens, such as 
spironolactone, finasteride and cyproterone acetate) within 1 month before 
baseline.
o
Oral contraceptives can be continued if stable for the last 3 months before 
baseline if stable in dose and dosing regimen and type (brand) and if the 
patient plans to continue throughout the study period. 

Previous treatment with biologics (such as anti-TNFα agents or anti-IL-1) 
within 3 months prior to baseline; Anti-IL-12/23 blocking agents (such as 
briakinumab and ustekinumab or p19 antibodies) within 6 months prior to 
baseline.

Any previous treatment with IL-17 or IL17R blocking agents, including, but not 
limited to secukinumab, ixekizumab or brodalumab.

Use of oral retinoids (in particular isotretinoin) within the last 6 months prior to 
baseline.

Previous surgical, physical (such as ThermaClear™), light (including blue or 
UV light, photodynamic therapy [PDT]) or laser therapy within 4 weeks prior to 
baseline. After baseline, use of any tanning device, or excessive exposure to 
sun [with intention to tan], any handheld light device to treat skin or procedures 
for hair removal in the evaluated areas (face, neck and trunk) are not 

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permitted.

Use of facial medium depth chemical peels (excluding home regimens) within 
3 months prior to baseline.

Any live vaccines (this includes nasal-spray flu vaccine) starting from 6 weeks 
before baseline

Any other forms of acne, such as:
o
Presence of cysts and severe nodulocystic acne, and any acne type with a 
high risk of severe scarring.
o
Secondary acne, including drug induced acne.
o
Acne associated with known hormonal imbalances such as polycystic 
ovaries, Cushing syndrome, congenital adrenal hyperplasia (CAH), etc. 
o
Acne as part of a known genetic syndrome.
o
Extensive (acne) keloids and hypertrophic scarring making clinical 
evaluation difficult.
o
Hidradenitis suppurativa, also called acne inversa.
o
Other forms of acne rosacea, peri-oral dermatitis and gram-negative 
folliculitis.

History of severe systemic Candida infections or evidence of Candidiasis in 
the 2 weeks prior to baseline.

At screening, history or symptoms of malignancy of any organ system 
Evidence of active tuberculosis at screening. 

Patients with known active Crohn’s disease

History of immunodeficiency diseases (positive Hepatitis B surface antigen or 
Hepatitis C test result at screening)

Pregnant or nursing (lactating) women, where pregnancy is defined as the 
state of a female after conception and until the termination of gestation, 
confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.

Women of child-bearing potential, defined as all women physiologically 
capable of becoming pregnant, unless they are using highly effective methods 
of contraception during dosing and for 13 weeks after stopping medication.
Study 
treatment
Treatment group 1:
Treatment period 1 (12 weeks): CJM112  high dose 
 monthly
Extension period 2 (12 weeks): CJM112  high dose 
 monthly
Treatment group 2:
Treatment period 1 (12 weeks): CJM112  low dose 
 monthly
Extension period 2 (12 weeks): CJM112  low dose 
 monthly
Treatment group 3:
Treatment period 1 (12 weeks): Placebo monthly
Extension period 2 (12 weeks): CJM112  low dose 
 monthly or CJM112  
Efficacy/PD 
assessments
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Key safety 
assessments

AE monitoring

Physical examinations

Monitoring of laboratory markers in blood and urine

ECG

Vital signs
Other 
assessments
Data analysis
The log transformed inflammatory facial lesion count will be analyzed using a 
Bayesian mixed effect model for repeated measures (MMRM), with log 
transformed baseline inflammatory facial lesion count as a covariate; treatment 
group, visit, treatment group by visit interaction and log transformed baseline 
inflammatory facial lesion count by visit interaction as fixed effects and an 
unstructured covariance structure will be used. 
Efficacy criteria (only for primary objective) 

If there is at least 90% probability that the treatment effect of CJM112 at Week 
12 is better than placebo and

If there is at least 50% probability that the treatment effect at Week 12 is at 
least 30% (0.357 in the log scale) in favor of CJM112.
Futility criterion 

If there is at least 60% probability that the treatment effect of CJM112 at 
Week 12 is worse than placebo.
The posterior estimates of the treatment effect and the treatment difference 
(along with its 90% credibility interval) at each visit (with Week 12 being of primary 
interest) will be provided. The results will be reported in terms of ratio of geometric 
means. 
 
Key words
Acne, efficacy, safety, PK
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1
Introduction
1.1
Background
The most relevant data for the present study are summarized in the sections below. 
For detailed information, please refer to the Investigator's Brochure (IB).
Moderate to severe inflammatory acne is a debilitating disease, with visible inflammatory 
lesions on the face and subsequent risk of permanent scars. The current treatment is often a 
combination or association of several topical treatments (such as topical retinoids and 
antibacterials such as benzoylperoxide and antibiotics) with oral antibiotics, and/or hormonal 
treatment or retinoids, such as isotretinoin. However, oral antibiotic and hormonal treatments 
are often only moderately effective, and isotretinoin, while effective in many cases, is 
associated with severe side effects, including teratogenicity, but also suicidal ideation, bone 
development issues, or increase of blood lipids. These are all sensitive side effects for a young 
adult. The side effects and the associated administrative hurdles due to pregnancy prevention 
programs in many countries preclude many patients to receive adequate effective treatment.
Relevant data summary
It is more and more recognized that inflammatory acne is not an infectious disease, but rather 
an inflammatory skin disease, in which Propionibacterium acnes (P. acnes) and innate 
immunity play critical roles (Das and Reynolds 2014). Recently the role of IL-17A in early 
acne lesions has been demonstrated by upregulated IL-17A in lesional versus non-lesional 
acne skin, both at RNA as well as at protein level (Kelhälä et al 2014). In vitro data point to 
increased IL-17A production by T-cells that are stimulated by P acnes. This P acnes induced 
increase of IL-17A was decreased by retinoids, a classical anti-acne treatment 
(Agak et al 2014). Serum IL17A is increased in acne patients and reduced by effective 
treatment after 12 weeks (Karadag et al 2012). In addition, beta-defensin-2, a main 
downstream marker for the IL-17A pathway, was shown to be increased in serum of patients 
and decreased after successful treatment (Borovaya et al 2014). Together these data frame 
evidence that an anti-IL-17A therapeutic strategy may be useful in patients with moderate to 
severe inflammatory acne.
CJM112 is an affinity matured fully human monoclonal antibody (mAb) that demonstrates 
high affinity to IL-17A and IL-17AF. Its potency is higher as compared to a recently approved 
anti-IL-17A blocker, secukinumab.
 
The preliminary clinical safety and efficacy 
of CJM112 was investigated in a First in Human (FIH) study in psoriasis patients, which 
showed a positive outcome, as patients receiving the high doses achieved responder rates 
(75% in improvement of the Psoriasis Area and Severity Index; PASI75) with single doses 
 
  The clinical efficacy was sustained over several months. The multiple dose 
therapeutic regimens over 12 weeks achieved similar PASI reductions as seen with 
secukinumab, but with roughly 4 to 7-fold lower doses (see Section 1.3.1 for further details).
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While overall CJM112 was well tolerated in the FIH study, the only relevant safety finding 
from this study is an expected slight increase of general infections during treatment with 
CJM112. This effect may be dose-dependent with increasing multiple doses of CJM112. 
There was no pattern of any special kind of infections, and most infections were upper 
respiratory tract infections. No opportunistic infections and no fungal infections occurred.
This proposed proof of concept (PoC) clinical study in moderate to severe inflammatory acne 
patients is a placebo-controlled, randomized, subject and investigator blinded, multi-center 
study with three parallel groups receiving monthly administrations of CJM112 in two dosage 
regimens or its placebo over a 24 week treatment period. While this is the first time testing an 
anti-IL-17A in this disease, it is anticipated that all doses tested would have at least a minimal 
beneficial effect, based on effects at similar dose levels seen in another skin disease, psoriasis. 
It is anticipated that the clinical safety at these doses is similar to that observed with other 
anti-IL-17A compounds, which seems appropriate for young adults and thus is anticipated to 
be superior to the one of oral isotretinoin, often used in this indication.
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1.3
Clinical data
The most relevant data for the present study are summarized in the sections below. 
For detailed information, please refer to the IB.
1.3.1
Human safety and tolerability data
First in Human study in patients with moderate to severe plaque type psoriasis
Clinical development of CJM112 was initiated in a FIH study in patients with chronic plaque 
type psoriasis (CCJM112X2101). The initial single ascending dose (SAD) study (Part 1) was 
conducted in 5 cohorts with single doses between 5 mg and 450 mg s.c. with each 4 treated 
with active and 2 with placebo. An additional single dose extension cohort was planned for 
50 mg (n=8 active and n=4 placebo). A subsequent multi-dose part in parallel arms with 
active (secukinumab) and placebo controls and 4 different treatment regimens for CJM112 
(Part 2) has been completed. 
 
 
 
 
An additional clinical trial in patients with moderate to severe hidradenitis suppurativa is 
ongoing and has completed recruitment. 
 
 
 
 
 
 
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1.4
Study purpose
The study is designed primarily to assess preliminary efficacy and safety of CJM112 in 
patients with moderate to severe inflammatory acne, and to determine if CJM112 has an 
adequate clinical profile for further clinical development. In addition, sustainability of 
response and dose relationship will be explored.
2
Study objectives and endpoints
2.1
Primary objective
Primary objective
Endpoints related to primary objective

To assess the efficacy of CJM112 
versus placebo on facial 
inflammatory lesion counts in 
patients with moderate to severe 
inflammatory acne

Total inflammatory facial lesion count at week 12
2.2
Secondary objective(s)
Secondary objective(s)
Endpoints related to secondary objective(s)

To assess the safety and 
tolerability of CJM112 in patients 
with moderate to severe 
inflammatory acne

Number and severity of AEs

Safety and tolerability assessments including 
general safety parameters (laboratory parameters, 
physical examination, vital signs, ECG assessed 
at baseline and repeatedly until study completion 
visit.

To assess the PK of CJM112 in 
patients with moderate to severe 
acne

Cmin,ss (multiple doses) from serum 
concentration data (non-compartmental analysis)
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3
Investigational plan
3.1
Study design
This is a randomized, placebo-controlled, subject and investigator blinded, multi-center, 
non-confirmatory, parallel-group, proof of concept study in patients with moderate to severe 
inflammatory acne. After an initial screening period (up to 4 weeks), the study will be 
conducted in 2 consecutive treatment periods, each of 12 weeks, to show clinical efficacy in 
treatment period 1, and potential sustainability of response in extension period 2. At the 
beginning of treatment period 1, patients will be randomized to one of the 3 treatment groups 
for the first 12 weeks only:
1.
 CJM112 s.c. at monthly intervals.
2.
 CJM112 s.c.at monthly intervals.
3. Placebo s.c. at monthly intervals.
At the end of treatment period 1, all patients will be offered the opportunity to remain in the 
study for the extension period 2. Patients who enter extension period 2 will receive the 
following treatments:

Treatment Period 1, 
 Extension Period 2,

Treatmend Period 1, 
 Extension Period 2, 

Treatment Period 1, Placebo. Extension Period 2, 
 via re-
randomization
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Study population
The patients included in the study are patients with moderate to severe inflammatory acne
who have previously failed other systemic therapies. There is no universally accepted 
classification of moderate to severe inflammatory acne.  A minimal count of 25 facial 
inflammatory lesions (papules, pustules, nodules) is needed for inclusion, which is similar to 
other studies in this indication (Fleischer et al 2006). For this study, no more than 5 facial 
nodules are accepted to exclude severe cases of nodulo-cystic acne, often associated with a 
high potential for scarring. Included patients should be otherwise in good health as determined 
by medical history and respect specified washout periods for anti-acne treatments (see 
Section 4.2 and Section 5.2). The chosen wash-out periods for anti-acne treatments are similar 
to what was done in other phase 3 programs in moderate to severe acne (Fleischer et al 2006; 
see as well sarecycline trials such as ClinicalTrial.gov, NCT02322866 2014). 
To target a typical moderate to severe inflammatory acne population in adults, patients 18 - 45 years
of age will be included. The upper age group is consistent with diagnosis of inflammatory 
acne. 
To limit variability in exposure to +/- 40% (based on AUCtau,ss; from preliminary/draft 
modeling exercise with reference body weight of 70 kg) a body weight range of 50 to 120 kg 
was selected for inclusion.
Clinical and other endpoints
It is assumed that the anti-inflammatory effect with an anti-IL-17A compound is the clinically 
most pronounced effect. Consequently, inflammatory lesion count is the primary endpoint, as 
outlined by CDER 2005. Inflammatory lesions are defined as papules, pustules and nodules. 
As counts on the face are best validated, the count will focus on the face, but other areas, such 
as truncal (upper chest and upper back and neck), will be assessed as well, when feasible.
In addition to lesion counting, the investigator's global assessment (IGA) for the face will be 
used as exploratory assessment of efficacy, in order to determine the clinical responder rate 
(achievement of clear or almost clear; or 2 grade improvement from baseline; CDER 2005. 
Other endpoints include global assessments on non-facial areas, such as the comprehensive 
acne severity scale (CASS), as described by (Tan et al 2007), as well as nodule counts.
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The clinical counts will be complemented in selected sites by standardized serial photographic 
imaging (such as Visia CR™), which provides the possibility of a central expert read and / or 
semi-automatic lesion counting. Imaging may be performed in different modalities and in 
particular the surface area of redness or area of inflammation may be explored as reflecting 
clinical inflammation. In selected sites, fluorescence imaging may explore a potential effect 
on P. acnes colonization on the skin (such as Visia CR™imaging).
As this is the first time that an anti-IL-17A inhibitor is tested in this population, 
 
Treatment arms and study methodology
The primary endpoint is a comparison of facial inflammatory lesion counts at week 12, an 
established duration period for anti-acne treatments, but other time points will be explored. 
Many acne treatments, including isotretinoin, need longer treatment duration for full efficacy. 
However, in this moderate to severe acne population, the increased acne scarring risk in the 
face makes it difficult to include patients in a placebo controlled study with more than 
12 weeks duration, hence, it is planned to offer placebo-treated patients to be re-randomized
after 12 weeks to either the
 treatment group in extension period 2. As the 
placebo effect can be quite high (up to 30-40% reduction in inflammatory lesion count at 
week 12) and the endpoints dependent on the investigator assessment, a blinded study is 
deemed optimal to generate reliable data for treatment period 1, which are not influenced by 
investigator’s perception. Extension period 2 data may be influenced by a lower severity due 
to a long run-in and drop-outs, but may show a similar trend. Given the high placebo effect, a 
parallel comparison is preferred over a cross over design.
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The randomization scheme overall is planned to be 1:1:1. This ensures that groups are 
balanced and the interpretation of results is possibly more robust. However, unbalanced 
randomization will be used at the start of trial to enhance early comparison of 
 vs placebo 
and interim efficacy/futility assessment. A 3:1:3 randomization 
 will be 
used for the first 35 patients and thereafter 1:2:1 
 for the remaining 
40 patients. In case more than 75 patients are randomized to the study, the randomization ratio 
will be 1:1:1 after the first 75 patients. Patients who have been randomized to placebo group 
in treatment period 1 and agree to continue into extension period 2 will be re-randomized into the 
two active dosing groups for another 12 weeks treatment, again with randomization ratio 1:1.
3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
In the present study, the dose 
 
 is proposed to explore efficacy in the moderate to severe acne population, 
which corresponds to one dose 
 administration 
monthly, considered as practical and feasible for this population. It is anticipated that the 
onset of action in acne is seen within months and well within treatment period 1 and extension 
period 2, thus, no loading dose during the first month was selected. In adult psoriasis patients, 
a cumulative dose 
 over 12 weeks (with a loading dose over the first month) was 
safe and effective. This dose achieved a clear clinical reduction of the PASI75 responders 
(achieving a reduction of 75% over baseline in PASI score) of over 80% of the included 
patients in the 
 dose group.
 
 
 
 As outlined in Section 1.3.1, the safety 
signals in the HS population versus placebo are consistent with the safety data known from 
other anti-Il-17A blockers and previous results in psoriasis patients. While reducing the
frequency to monthly doses,
 has a reasonable chance to distribute even in 
typical acne lesions, such as papules, which are more superficial and smaller than nodules, 
where tissue distribution is assumed difficult.
To explore a preliminary dose-efficacy relationship, a lower dose regimen in this study 
 
 in moderate to severe acne patients
 
 is proposed. Indeed, in a previous study in psoriasis patients, 
 
weekly for the 1st month and then monthly for a total of 3 months, showed clear efficacy 
versus placebo. The 
dose is, thus anticipated to demonstrate potential efficacy in acne, 
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as the exposure should be close to the one tested in psoriasis patients. Indeed, the clinical 
potency difference between CJM112 
 and secukinumab 
in psoriasis is about 7-fold based on exposure, or about 4-fold based on dose, as demonstrated 
(preliminary modeling) in the psoriasis study. Thus, CJM112 
 roughly corresponds 
in terms of clinical potency to 
 secukinumab, another anti-IL-17A antibody, approved 
in psoriasis, psoriatic arthritis and ankylosing spondylitis. 
So far, in psoriasis patients, CJM112 has demonstrated typical IgG1 antibody disposition 
characteristics with dose-independent systemic clearance, and predictable PK. Body weight 
appeared to explain most of the inter-individual variability (in psoriasis), and bioavailability 
of the s.c. route was approximately 50% (based on preliminary/draft population modeling 
using SAD data from CCJM112X2101 study and historical secukinumab data). 
Treatment duration is referenced by the CDER 2005 to be at least 12 weeks despite the fact 
that maximum effects may not yet be achieved. Currently ongoing or completed studies with 
biologics 
have 
used 
a 
similar 
or 
slightly 
longer 
duration 
(such 
as 
ClinicalTrials.gov, NCT01498874 2011, with gevokizumab, an interleukin-1β antibody;
ClinicalTrials.gov, NCT01474798 2011 with Xilonix or RA-18C3, a monoclonal anti-IL-1α 
antibody and phase III studies using sarecycline, ClinicalTrials.gov, NCT02320149 2014 and 
ClinicalTrials.gov, NCT02322866  2014). Several studies in moderate to severe inflammatory 
acne show strong clinical effects at 6 months (in particular with isotretinoin, see 
Lee et al 2011, or hormonal treatment, see Lucky et al 1997). Although the primary endpoint 
is evaluated at week 12, patients who have been randomized to active treatment in treatment 
period 1 and decide to continue into extension period 2 will have receive another 12-week 
treatment, which may provide evidence of sustainability or even further improvement of 
clinical efficacy from week 12 up to week 24.
In order to reduce in this sensitive population the risk of persistent scarring on the face, 
placebo will not be used longer than 12 weeks. Thus, all patients randomized to placebo and 
who accept to continue will be re-randomized into an active treatment arm for extension 
period 2.
A safety follow-up period of 13 weeks is proposed for all patients since this corresponds to 
approximatively 5 half-lives, based on SAD data from psoriasis patients (CCJM112X2101).  
Patients who complete but decide not to continue after treatment period 1 would also be 
followed for another 13 weeks, just as those who complete extension period 2.
3.4
Rationale for choice of comparator
Often, acne patients are recruited for study entry at their worst severity and usually improve 
during the course of therapy, whether the therapy is active or placebo. Thus, to explore
efficacy of a new anti-acne drug, generally a demonstration of superiority to placebo using a 
double blind methodology is needed. In this trial, a matching placebo will be used.
No injectable approved anti-acne drugs exist.
Using a controlled and double blind design, a potential assessment bias will be reduced, the 
more as outcomes rely on subjective evaluation.
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3.5
Rationale for choice of background therapy
Acne is a disease where inflammatory lesions, such as papules and pustules appear and 
disappear in irregular intervals and numbers.  Similarly, treatment adherence for anti-acne 
treatment is considered poor (Thiboutot et al 2009). In order to avoid as much as possible 
potential confounders due to intermittent treatment in treatment period 1, all medication to 
treat acne or acne inflammation is to be washed out and thus no background therapy is needed 
(see relevant exclusion criteria, (Section 4.2) and prohibited treatment, (Section 5.2)).
In extension period 2, topical anti-acne treatments are permitted (see Section 5.2).
3.7
Risks and benefits
CJM1112 has been well tolerated in the FIH study in patients with plaque psoriasis including 
28 patients exposed to a single dose 
 and 42 patients exposed to 
multiple doses of CJM112 
 over 
12 weeks in comparison to secukinumab and placebo (n=6 each). In addition, 33 patients with 
moderate to severe HS have been exposed to CJM112 
 weekly for one month and bi-
weekly for 4 months. As described in Section 1.3.1, the safety signal even at these high doses 
did not reveal new concerns. As expected, the safety profile of CJM112 appears comparable 
to that of secukinumab, another anti-IL-17A monoclonal antibody, which has data from an 
extensive number of patients with longer exposure durations and is now approved in three 
indications (see Section 1.3). Primarily non-serious upper respiratory tract infections have 
been observed (in particular pharyngitis and nasopharyngitis) more frequently with CJM112
than placebo, and a potential dose-dependent increase in rates of infection was observed in the 
multi-dose study part over 12 weeks. Small, incremental risks in Candida infections are 
reported for IL-17 blocking agents but have not been observed so far for CJM112. 
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Hypersensitivity reactions have not been observed so far for CJM112 but their future 
occurrence cannot be excluded.
There were no SAEs that are considered expected for CJM112. In clinical studies, urticaria 
and one case of anaphylactic reaction to secukinumab were observed. However, none of these 
cases were observed with CJM112.
In study CCJM112X2101, in Part I (SAD), four patients (14.3%) treated with CJM112 were 
ADA-positive (patients with at least one treatment induced ADA-positive sample at any time 
during the treatment or follow-up observation period). ADAs may have affected the PK 
profile of one patient
 and an effect on the PASI profile cannot be 
excluded. For two ADA-positive patients 
 and for the one 
 
 ADAs did not appear to have affected their PASI profiles when compared to other 
patients in the same cohort. In Part 2 (multiple dose), six patients (14.3%) treated with 
CJM112 were ADA-positive and the frequency of ADA-positive subjects appeared to have an 
inverse correlation with the dose and was 5/11 subjects (45.5%), 0/10 subjects, 1/10 subjects 
(10%) and 0/11 subjects, 
 
 For 3 patients 
 while the positive ADA response was 
generally characterized with low titers, it cannot be excluded that the ADA response has had a 
consequence on the target capture profile or on the PASI reduction time course. For the ADA-
positive patient 
 the presence of ADAs is unlikely to have affected 
the PASI reduction time course.
Due to the same mechanism of action and similar class of drugs (fully human monoclonal 
antibodies of IgG1 type) potential risks identified in the large clinical experience for 
secukinumab are of relevance for CJM112, as the safety profile of CJM112 still remains 
preliminary in early stages of development. The most frequently reported adverse drug 
reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis, 
rhinitis). Most of the events were, however, mild or moderate in severity.
In addition to the above mentioned events, injection site reactions, elevations in liver enzymes, 
drops in neutrophil counts and ECG abnormalities have been observed sporadically and very 
rarely in secukinumab trials. These cases have not yet been observed with CJM112. 
Nevertheless, these constitute events that may be observed and should be monitored routinely, 
as with any investigational biologic treatment. 
As secukinumab was ineffective in a phase II trial in patients with moderate to severe 
Crohn’s disease, patients with active Crohn’s disease will be excluded from this study 
(see Hueber et al 2012).
Women of child bearing potential (WOCBD) and sexually active males should be informed 
that taking the investigational drug may involve unknown risks to the fetus if a subject or their 
partner were to become pregnant during the study. He/she must agree that in order to 
participate in the study they will adhere to the highly effective contraception requirement for 
the duration of the study and for 13 weeks after the last dose. If there is any question that the 
subject will not strictly comply, he/she should not be entered in the study.
Of note, for the present study population, moderate to severe acne, co-morbidities may be 
observed more frequently than in the overall population, such as depression and suicidal 
ideation (Purvis et al 2006, Halvorsen et al 2011). However, frequency of suicidal ideation, 
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even if difficult to be compared, seems to be in a similar range as for other chronic skin 
diseases, such as psoriasis (Picardi et al 2013, Kurd et al 2010). Thus, no specific suicidality 
assessment is being performed. 
Treatment for AEs should follow general guidelines for standard-of-care, and is at the 
discretion of the investigator or treating physician. There are no specific treatment 
recommendations for AEs that may possibly occur in in this trial.
The expected benefit is that CJM112 shows some level of clinical efficacy in reducing 
inflammatory acne lesions. This is based on the assumption that multiple and even single 
doses of CJM112 
 had sustained clinical efficacy in psoriasis patients for 
over 3-4 months (see Section 1.3.). As no previous studies using an IL-17A inhibitor have 
been conducted, this benefit is difficult to quantify. Patients randomized to placebo are 
unlikely to benefit from the trial in treatment period 1, even if generally the placebo effect 
accounts for 20-30% of lesion reduction. All patients will be exposed in extension period 2 to 
CJM112 and may have a potential benefit from the proposed therapy. Furthermore, subjects with 
clinical worsening of their acne and/or any active ongoing scarring are to be discontinued from
study treatment (see Section 7.2) to benefit from approved anti acne treatments, if needed. 
The risks to subjects in this trial will be minimized by adherence to the inclusion/exclusion 
criteria, close clinical monitoring, and adequate safety follow-up, which has been determined 
based on the expected half-life of CJM112 in acne patients (i.e. similarity with psoriasis 
patients), to capture late occurring AEs. Based on available clinical knowledge about effects 
of IL-17A targeting therapies, it is anticipated that the risks to experience AEs is comparable 
to the experience with secukinumab.
Due to the early stage of development, there may be unknown risks of CJM112 which may be 
serious and/or unforeseen. 
Additional risks are related to the procedures of the trial, such as blood sampling and skin 
biopsy sampling. During the collection of blood samples, patients may experience pain and/or 
bruising at the injection site. In addition, although rare, localized clot formation, infections 
and nerve injuries may occur. Lightheadedness or fainting may also occur during or after the 
blood draw. The skin biopsy will be in general a punch biopsy, commonly performed in 
dermatological practice, and performed under local anesthesia. On rare occasions, local 
bruising, bleeding, pain, discomfort and a low risk of infection, wound healing difficulties or a 
scar are possible. Biopsies will be performed on non-facial areas, generally on upper back or 
neck.
3.7.1
Blood sample volumes
A maximum of approximately 350mL of blood is planned to be collected over a period of 
36 weeks, from each subject as part of the study. Additional samples for monitoring of any 
safety findings would be in addition to this. This is not considered to be a risk for this 
population.
All blood samples will be taken by direct venipuncture in a forearm vein contra-lateral to the 
site of subcutaneous injection. All sampling should have a unique sample numbering. 
The actual sample collection date and time will be recorded on the immunogenicity blood 
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collection page of the CRF. Sampling problems will be noted on the comments field of the 
CRF.
Timings of blood sample collection are outlined in the Assessment Schedule.
A summary blood log is provided in the SOM, together with instructions for all sample 
collection, processing and storage and shipment information.
See Section 8.8 regarding the potential use of residual samples. 

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4
Population
The study population will be comprised of male and female subjects, aged 18-45 years of age, 
with moderate to severe inflammatory acne. A total of approximately 75 patients will be 
randomized. 
 
The investigators must ensure that all patients being considered for the study meet the 
eligibility criteria. No additional criterion should be applied by the investigators, in order that 
the study population will be representative of all eligible patients.
4.1
Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Written informed consent must be obtained before any study procedures are performed.
2. Male and female subjects aged 18 to 45 years of age included, and otherwise in good 
health as determined by medical history, physical examination, vital signs, ECGs and 
laboratory tests at screening.
3. Body weight between 50 and 120 kg, inclusive at screening.
4. Patients with papulo-pustular acne vulgaris with between 25 and 100 facial inflammatory 
lesions (papules, pustules and nodules), and presence of non-inflammatory lesions 
(open and closed comedones) in the face at screening and baseline, who have failed
systemic therapy for inflammatory acne.
5. No more than 5 facial inflammatory nodules at screening and baseline. 
6. Investigator's Global assessment (IGA) score of at least moderate (3) acne severity on the face at 
screening and baseline.
7. Able to communicate well with the investigator, to understand and comply with the 
requirements of the study.
4.2
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study:
1. Use of investigational drugs at the time of screening, or within 4 weeks or 5 half-lives of 
baseline, whichever is longer; or longer if required by local regulations.
2. Use of any topical anti-acne prescription treatment within 2 weeks and any over the 
counter (OTC) anti-acne treatment within 1 week of baseline (use of medicated (anti-acne)
creams, medicated cleansers or medicated soaps is prohibited for treatment period 1).
3. Use of any oral/systemic treatment for acne, including oral antibiotics, dapsone, oral zinc 
within 4 weeks prior to baseline.
4. Use of systemic or lesional injected (for acne) corticosteroids or systemic 
immunomodulators (such as cyclosporine, methotrexate, azathioprine, etc.) within 
4 weeks before baseline (see Section 5.2).
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5. Use of any systemic hormonal treatment (in particular anti-androgens, such as 
spironolactone, finasteride and cyproterone acetate) within 1 month before baseline.
Oral contraceptives can be continued if stable for the last 3 months before baseline and if 
stable in dose and dosing regimen and type (brand) and if the patient plans to continue 
throughout the study period. 
6. Previous treatment with biologics (such as anti-TNFα agents or anti-IL-1) within 
3 months prior to baseline; Anti-IL-12/23 blocking agents (such as briakinumab and 
ustekinumab or p19 antibodies) within 6 months prior to baseline.
7. Any previous treatment with IL-17 or IL17R blocking agents, including, but not limited 
to secukinumab, ixekizumab, bimekizumab or brodalumab.
8. Use of oral retinoids (in particular isotretinoin) within the last 6 months prior to baseline.
9. Previous surgical, physical (such as ThermaClear™), light (including blue or UV light, 
photodynamic therapy [PDT]) or laser therapy within 4 weeks prior to baseline. 
After baseline, use of any tanning device, or excessive exposure to sun [with intention to 
tan], any handheld light device to treat skin or procedures for hair removal in the 
evaluated areas (face, neck and trunk) are not permitted.
10. Use of facial medium depth chemical peels (excluding home regimens) within 3 months 
prior to baseline.
11. Any live vaccines (this includes nasal-spray flu vaccine) starting from 6 weeks before baseline.
12. Any other forms of acne, such as:

Presence of cysts and severe nodulocystic acne, and any acne type with a high risk of 
severe scarring.

Secondary acne, including drug induced acne (steroids, cloracne, lithium, EGFR-
inhibitors [cetuximab, erlotinib, panitumumab und gefitinib, etc.], associated with 
acneiform eruptions, including PRIDE syndrome).

Acne associated with known hormonal imbalances such as polycystic ovaries, 
Cushing syndrome, congenital adrenal hyperplasia (CAH), androgen-secreting tumors, 
and acromegaly. Patients with signs/symptoms of hyperandrogenism such as 
hirsutism should undergo hormonal status assessment at the discretion of the 
investigator.

Acne as part of a known genetic syndrome, such as SAPHO, PAPA, PASH or other 
variants possibly associated with PSTPIP1 gene.

Extensive (acne) keloids and hypertrophic scarring making clinical evaluation 
difficult.

Hidradenitis suppurativa also called Acne inversa.

Other forms of acne rosacea, peri-oral dermatitis and gram-negative folliculitis.
13. Any severe, progressive or uncontrolled medical or psychiatric condition or other factors 
at randomization that in the judgment of the investigator prevents the patient from 
participating in the study.
14. History of hypersensitivity or allergy to the investigational compound/compound class 
being used in this study.
15. Active systemic infections (other than common cold) during the 2 weeks prior to baseline.

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16. History of severe systemic Candida infections or evidence of Candidiasis in the 2 weeks 
prior to baseline.
17. At screening, history or symptoms of malignancy of any organ system (except for a 
history of basal cell carcinomas and/or up to 3 squamous cell carcinomas of the skin, if 
successful treatment has been performed, with no signs of recurrence; actinic keratoses, if 
present at screening, should be treated according to standard therapy before 
randomization), treated or untreated, within the past 5 years, regardless of whether there 
is evidence of local recurrence or metastases.
18. Evidence of active tuberculosis at screening. All patients will be tested for tuberculosis 
status using a blood test (QuantiFERON®-TB Gold In-Tube). Patients with evidence of 
tuberculosis may enter the trial after adequate treatment has been started according to 
local regulations.
19. Patients with known active Crohn’s disease.
20. History of immunodeficiency diseases, including a positive HIV (ELISA and Western 
blot) test result at screening.
21. A positive Hepatitis B surface antigen or Hepatitis C test result at screening
22. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
hCG laboratory test.
23. WOCBP, defined as all women physiologically capable of becoming pregnant, unless 
they are using highly effective methods of contraception during dosing and for 13 weeks 
after stopping medication. Highly effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject). Periodic abstinence (i.e., calendar, ovulation, symptothermal, postovulation 
methods) and withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking 
study treatment. In case of oophorectomy alone, only when the reproductive status of 
the woman has been confirmed by follow up hormone level assessment

Male sterilization (at least 6 months prior to screening). The vasectomized male 
partner should be the sole partner for that subject

Use of oral, injected or implanted hormonal methods of contraception or placement of 
an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal 
contraception that have comparable efficacy (failure rate <1%), for example hormone 
vaginal ring or transdermal hormone contraception
In case of use of oral contraception women should have been treated with the same pill 
and dose for a minimum of 3 months before taking study treatment.
Women are considered post-menopausal and not of child bearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral 
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. 
In the case of oophorectomy alone, only when the reproductive status of the woman has 
been confirmed by follow up hormone level assessment is she considered not of child 
bearing potential.

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24. History of drug or alcohol abuse within the 12 months prior to dosing.
25. Donation or loss of 400 ml or more of blood within 8 weeks prior to baseline, or longer if 
required by local regulation.
26. Inability or unwillingness to undergo repeated venipunctures (e.g., due to poor 
tolerability or lack of access to veins). 
27. No additional exclusions may be applied by the investigator, in order to ensure that the 
study population will be representative of all eligible patients.
5
Restrictions for Study Subjects
During recruitment, screening/informed consent review, and baseline visit, the subjects must 
be informed and reminded of the restrictions outlined in this section.
5.1
Contraception requirements
As the reproductive toxicity studies are not yet final, highly effective contraception is 
proposed for all trials with CJM112 that include WOCBP, until further information is 
available. WOCBP, defined as all women physiologically capable of becoming pregnant, 
unless they are using highly effective methods of contraception during dosing and for 
13 weeks (= 5 times the mean terminal half-life in psoriasis patients) after stopping CJM112.
Highly effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. 
Periodic abstinence (i.e., calendar, ovulation, symptothermal, postovulation methods) and 
withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow up hormone level assessment

Male sterilization (at least 6 months prior to screening). The vasectomized male partner 
should be the sole partner for that subject

Use of oral, injected or implanted hormonal methods of contraception or placement of an 
IUD or IUS or other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example hormone vaginal ring or transdermal hormone 
contraception.
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment.

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5.2
Prohibited treatment
Table 5-1
Prohibited treatment
Medication/treatment
Action to be taken
Required wash-out (prior 
to randomization/first 
treatment)
Exposure to any IL-17 or IL-17R 
blocking agents
Do not include in the 
study/discontinue study 
treatment
Exclusion criterion
TNFα blockers such as adalimumab 
and infliximab
Discontinue study treatment
Wash-out: 3 months
IL-12 or IL-23 blocking agents such as 
briakinumab and ustekinumab, including 
investigational p19 antibodies
Discontinue study treatment
Wash-out: 6 months
Any biologics, other than above
Discontinue study treatment
Wash-out: 3 months or at 
least 5 times the half life
Any systemic immunosuppressant or 
immunomodulator, such as 
cyclosporine, methotrexate, 
cyclophosphamide, azathioprine, 
corticosteroids (includes local 
injections), etc.
Discontinue study treatment 
(unless local injections: to be 
discussed with sponsor on 
case by case basis)
Wash-out: 4 weeks
Any systemic treatment with antibiotics 
(longer than 2 weeks), in particular 
tetracyclines and/or macrolides, but as 
well other oral anti-acne treatment such 
as dapsone and zinc. These treatments 
are accepted for periods shorter than 2 
weeks, if medically indicated.
Discontinue study treatment 
if antibiotic treatment (not for 
acne) is longer than 2 weeks
All other cases to be 
discussed with Sponsor on 
case by case basis
Wash-out: 4 weeks
Use of any systemic hormonal 
treatment (with the exception of 
hormonal contraceptive) (including anti-
androgens, such as spironolactone, 
finasteride and cyproterone acetate) 
within 1 month before baseline.
To be discussed with 
sponsor on case by case 
basis
Wash-out of 1 month
Oral contraceptives can be continued if 
stable for the last 3 months before 
baseline if stable in dose and dosing 
regimen and type and if the patient 
plans to continue throughout the study.
To be discussed with 
sponsor on case by case 
basis
Wash out for change in dose, 
regimen or type: 3 months
Systemic retinoids, in particular 
isotretinoin
Discontinue study treatment
Wash-out: 6 months
Comedo extraction, electrocautery, and 
medical chemical peels using glycolic 
acid, salicylic acid, and trichloroacetic 
acid (for acne or acne lesions and /or 
done on areas of evaluation (face, back, 
chest, shoulder, etc.))
Discontinue study treatment 
for medium depth facial peels
Sporadic local treatment to 
be discussed with sponsor 
on case by case basis
No wash-out
Medium depth peels 
3 months wash out

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Medication/treatment
Action to be taken
Required wash-out (prior 
to randomization/first 
treatment)
Surgical or physical (such as 
ThermaClearTM ) light and laser therapy 
(including blue light, use of handheld 
devices, tanning devices or 
photodynamic therapy [PDT]) on area of 
evaluation. 
After baseline, use of any tanning 
device, or excessive exposure to sun 
[with intention to tan], any handheld light 
device to treat skin or procedures for 
hair removal in the evaluation areas are 
not permitted.
To be discussed with 
sponsor on case by case 
basis.
Wash-out: 4 weeks
Any live vaccines (this incl. nasal-spray 
flu vaccine)
Discontinue study treatment
6 weeks
Any topical for acne on area for 
evaluation (face, back, chest, shoulder, 
neck), including retinoids (such as 
adapalene, tazarotene, isotretinoin or 
tretinoin), antibacterial and antibiotics 
(such as benzoyl peroxide, clindamycin 
or erythromycin) and any other topical 
keratolytic or peeling agents (such as 
salicylic acid, or lactic acid) or any other 
anti-acne drug (such as dapsone, 
azelaic acid). These topicals include 
over the counter (OTC) products for 
acne, such as medicated emollients, 
medicated cleansers or medicated 
soaps.  
To be discussed with 
sponsor on case by case 
basis for treatment period 1.
In the extension period 2, 
topical anti-acne treatment is
allowed, if needed (to be 
recorded as concomitant 
medication). 
Wash out for 1 week 
(for OTC products) and for 
2 weeks (for prescription 
drugs (RX)).
5.3
Dietary restrictions and smoking
In this study, no particular dietary restrictions are required. However, acne patients are 
recommended to follow a healthy diet, but will not receive specific dietary restrictions 
5.4
Other restrictions
During the trial, all patients should avoid excessive sun bathing, including for the purpose of 
tanning. To avoid sunburn, appropriate sun avoidance and protection should be exercised. 
In particular, patients with outdoor activity should be counseled regarding appropriate sun 
avoidance and protection.
No procedures to reduce acne lesions are allowed, including chemical peels, laser or light 
procedures and surgery (see Section 5.2).

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Topical products used on the area of evaluation, such as emollients, cleansers, day creams etc. 
used by the patient should be checked by the investigator to see if she/he can continue using it, 
to avoid use of any medicated anti-acne products in treatment period 1 (see Section 4.2. or 
Section 5.2). Use of facial medium depth chemical peels (excluding home regimens) within 
3 months prior to baseline are prohibited.
Planned vaccination is allowed, unless live vaccines are needed. Any live vaccines 
(this includes nasal-spray flu vaccine) should be initiated at least 6 weeks before baseline.
6
Treatment
6.1
Study treatment
Details on the requirements for storage and management of IMP, and instructions to be 
followed for subject numbering, prescribing/dispensing and taking IMP are outlined in the 
SOM.
6.1.1
Investigational treatment and placebo
Table 6-1
Overview of Investigational treatment
Study drug 
name
Formulation
Appearance
Unit dose
Packaging
Provided by
CJM112
Liquid in Vial
clear liquid
Individual Patient 
Packs
Novartis
Placebo to 
CJM112
Liquid in Vial
clear liquid
Individual Patient 
Packs
Novartis
6.1.2
Additional study treatment
No additional treatment beyond investigational treatment and placebo are included in this trial.
6.2
Treatment arms
Overall subjects will be assigned to one of the following 3 treatment arms in a ratio of 1:1:1.
Study treatments are defined as:

CJM112 
 once monthly for a total of up to 7 doses 

CJM112 
 once monthly for a total of up to 7 doses

Placebo for a total of up to 3 doses, followed by re-randomization into either active 
treatment group for extension period 2 for a total of up to 4 active doses
Both CJM112 and placebo will be provided as liquid in vial according to the dose that is 
required. Placebo will be matched by volume and number of syringes/injections to maintain 
double-blind. Details on the study medication preparation will be provided in the 
Pharmacy Manual provided separately. Dosing is by s.c. administration at time points
specified in the Assessment Schedule. 
Unbalanced randomization will be used at the start of trial to enhance early comparison of 
CJM112 vs placebo and interim efficacy/futility assessment. A 3:1:3 randomization 
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 will be used for the first 35 patients and thereafter 1:2:1 
 for the remaining 40 patients. In case more than 75 patients are 
randomized to the study, the randomization ratio will be 1:1:1 after the first 75 patients.
6.3
Treatment assignment and randomization
Randomized treatment will be assigned to individual patients by way of a randomization 
number at the beginning of treatment period 1. At week 12 visit, patients who have been 
randomized to placebo group in treatment period 1 and also agree to continue in extension 
period 2 will again be assigned randomly to one of the two active treatment groups via a new 
randomization number.
The randomization number is only used to identify which treatment the patients have been 
randomized to receive. The Subject number assigned to a patient at screening remains the 
unique identifier for the patient throughout the study. For information on subject numbering, 
please see ‘Subject numbering’ section in the SOM.
Replacement randomization numbers will be in the same range of the initial randomization 
list. If a subject requires a replacement, the replacement subject will be assigned a 
randomization number corresponding to the original patient (e.g. Subject 6103 would replace 
Subject 5103). Any additional patients enrolled will use sequential subject numbering.
Patients who discontinued from study treatment before completion of Visit 201 assessments 
for reasons other than safety may be replaced by an equal number of newly enrolled patients, 
until sufficient number of completers per arm at week 12 is achieved (Section 11.7). 
Patients who discontinue from study treatment after week 12 will not be replaced. The 
observed dropout rate from the first 35 patients will be used to evaluate the final total 
recruitment needed.
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A subject 
randomization list will be produced by the Interactive Response Technology (IRT) provider 
using a validated system that automates the random assignment of subject numbers to 
randomization numbers. These randomization numbers are linked to the different treatment 
arms, which in turn are linked to medication numbers. A separate medication list will be 
produced by or under the responsibility of Novartis Drug Supply Management using a 
validated system that automates the random assignment of medication numbers to packs 
containing the investigational drug(s).
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office.
Follow the details outlined in the SOM regarding the process and timing of treatment 
assignment and randomization of patients.
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6.4
Treatment blinding
This is a subject and investigator-blinded study. Subjects and investigators will remain 
blinded to study treatment throughout the study, except where indicated below.
The identity of the treatments will be concealed by the use of study drugs that are all identical 
in packaging, labeling and schedule of administration, appearance, and odor.
Site staff
All site staff (including study investigator and study nurse) will be blinded to study treatment 
throughout the study.
Unblinding a single subject at site for safety reasons (necessary for subject management) will 
occur via an emergency system in place at the site (see Section 6.7).
Sponsor staff
The following unblinded sponsor roles are required for this study:

Unblinded BM bio-analyst (BM samples)

Unblinded PK bio-analyst (PK samples)
Both will receive a copy of the randomization schedule (via request to the Randomization 
Office), to facilitate analysis of the samples. They will provide the sample data to the study 
team under blinded conditions unless otherwise allowed.
All unblinded personnel will otherwise keep randomization lists and data or information that 
could unblind other study team members confidential and secure except as described above.
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Following final database lock all roles may be considered unblinded.
Table 6-2
Blinding levels
Role
Time or Event
Randomization 
list generated
Treatment 
allocation & 
dosing
Safety event 
(single subject 
unblinded)
Subjects/Patients
B
B
UI
Site staff
B
B
UI
Data Manager
B
B
UI
Monitor
B
B
UI
Drug Supply and 
Randomization Office
UI
UI
UI
Unblinded sponsor staff 
(see text for details)
UI
UI
UI
Statistician/statistical 
programmer/data 
analysts
B
B
UI
CTT and decision boards
B
B
UI
B Remains blinded
UI Allowed to be unblinded on individual patient level
6.5
Treating the subject
CJM112 will be administered to the subject via s.c. dosing. See the SOM for further details.
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems.
6.6
Permitted dose adjustments and interruptions of study treatment
Study 
treatment 
dose 
adjustments 
and/or 
interruptions 
are 
not 
permitted. 
Occasional interruptions in study treatment must be recorded as protocol deviations.
These changes must be recorded on the Dosage Administration Record Case Report Form 
(CRF).
6.7
Emergency breaking of assigned treatment code
Emergency code breaks must only be undertaken when it is required to in order to treat the 
subject safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a subject, he/she must provide 
the requested subject identifying information and confirm the necessity to break the treatment 
code for the subject. The investigator will then receive details of the investigational drug 
treatment for the specified subject and a fax or email confirming this information. The system 
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will automatically inform the study monitor for the site and the Study Team that the code has 
been broken.
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency.   The inves tigator 
will need to provide: 

protocol number

study drug name (if available)

subject number
In addition, the investigator must provide oral and written information to inform the subject 
how to contact his/her backup in cases of emergency when he/she is unavailable to ensure that 
un-blinding can be performed at any time.
An assessment will be done by the appropriate site personnel and sponsor after an emergency 
unblinding to assess whether or not study treatment should be discontinued for a given 
subject..
6.8
Treatment exposure and compliance
Pharmacokinetic parameters (measures of treatment exposure) will be determined in all 
subjects treated with CJM112, as detailed in Section 8.6.
6.9
Recommended treatment of adverse events
There are no known expected AE associated with CJM112 that would warrant specific 
treatment.  Necessary medication as well as surgical or physical treatment used to treat AEs 
must be recorded on the Concomitant medications/Significant non-drug therapies CRF. 
6.10
Rescue medication
No specific rescue treatments are planned for this study. Use of rescue medication must be 
recorded on the Concomitant medications/Significant non-drug therapies CRF.
6.11
Concomitant treatment
All prescription medications, OTC drugs and significant non-drug therapies (including laser 
or light / photodynamic therapy, physical therapy, chemical peel, medicated cleansers or 
surgery and blood transfusions) administered or taken within the timeframe defined in the 
entry criteria prior to the start of the study and during the study, must be recorded on the 
Concomitant medications/ Significant non-drug therapies section of the CRF.
Medication entries should be specific to trade name, the single dose and unit, the frequency 
and route of administration, the start and discontinuation date and the reason for therapy.

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7
Study completion and discontinuation
7.1
Study completion and post-study treatment
Each patient will be required to complete the study and thereafter no further study treatment 
will be made available to them.
Study completion is defined as when the last patient completes their Study Completion visit, 
and any repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator, or in the event of an early study termination decision, the 
date of that decision.
All patients should have safety follow-up for 12 weeks after the last treatment received, 
whenever possible. The information collected is kept as source documentation.  All SAEs 
reported must be reported as described in Section 9.2 and the SOM.  Documentation of 
attempts to contact the patient should be recorded in the source documentation.
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.
7.2
Discontinuation of study treatment
Individual Treatment Discontinuation Rules
Patients may voluntarily discontinue the study for any reason at any time. The investigator 
must discontinue study treatment for a given subjects, if, on balance, he/she believes that 
continuation would be detrimental to the patient’s well-being.
Study treatment must be discontinued under the following circumstances:

Patient withdraws consent

Pregnancy

Emergence of the following AEs (CTCAE grading v4.03): 

Grade 3 or higher allergic or hypersensitivity reaction

Acute, grade 3 or higher infection as judged by the investigator

Neutropenia grade 3 or higher

Clinical worsening of acne (worsening of at least one grade in the IGA, e.g. from severe to 
very severe) and/or any active ongoing scarring as per investigator judgement

Any other protocol deviation that results in a significant risk to the patient’s safety
Use of prohibited treatment as per Section 5.2 might result in treatment discontinuation 
(decision will be taken on case by case basis after consultation with Sponsor).
The appropriate personnel from the site and Novartis will assess whether treatment should be 
discontinued for any patient whose treatment code has been broken inadvertently for any reason.
Subjects who discontinue study treatment should NOT be considered withdrawn from the 
study UNLESS they withdraw their consent. Where possible, they should return for the
assessments as defined in the Assessment table for the post-treatment follow-up visits. 

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If they fail to return for these assessments for unknown reasons, every effort (e.g. telephone, 
e-mail, letter) should be made to contact them as specified in Section 7.1. 
7.3
Withdrawal of informed consent
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time.
Withdrawal of consent from the study is defined as when a patient:

Does not want to participate in the study anymore and

Does not want any further visits or assessments and

Does not want any further study related contacts and

Does not allow analysis of already obtained biologic material.
In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the patient’s decision to withdraw his/her consent and record 
this information.
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up.
7.4
Lost to follow-up
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator should show "due diligence" by 
documenting in the source documents steps taken to contact the subject, e.g. dates of 
telephone calls, registered letters, etc. A patient cannot be formally considered lost to follow-
up until his/her scheduled end of study visit would have occurred.
7.5
Study stopping rules
The study must be put on hold pending full safety data review if one or more of the following 
criteria are met:

Two or more investigational drug (CJM112)-related SAEs are reported

Other clinically significant events that in the opinion of the investigator or sponsor 
preclude to continue dosing (especially events that are suspected to be drug related, such 
as severe skin infections) 
In these cases, ad hoc internal experts will carefully evaluate the safety data of the entire study. 
The experts will recommend whether the study can be continued, should be stopped or if other 
safety measures need to be taken. The findings and recommendations of the internal experts 
will be documented and will be made available to the respective Institutional Review 
Board/Independent Ethics Committee (IRB/IEC).

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7.6
Early study termination by the sponsor
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit/ risk assessment of participating in the study, practical reasons (including 
slow enrollment), or for regulatory or medical reasons. Should this be necessary, patients must 
be seen as soon as possible and treated as a prematurely withdrawn patient. The investigator 
may be informed of additional procedures to be followed in order to ensure that adequate 
consideration is given to the protection of the patient's interests. The investigator will be 
responsible for informing IRBs/IECs of the early termination of the trial.

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8
Procedures and assessments
Table 8-1
Assessment Schedule
Study Epoch
Screening
Treatment Period 1
Extension Period 2
Post-treatment 
Follow-up
Visit Numbers1
V1
V101
V102
V1032
V201
V202
V203
V2042
V30116
V3022,16
Study Day(s)
-28 to -2
1
+2
29
-5 +5
57
-5 +5
85
-5 +5
113
-5 +5
141
-5 +5
169
-3 +3
218
-10 +10
260
-15 +15
Time (post-dose)
-
-
-
-
-
-
-
-
-
-
Informed consent
X
X
Inclusion / Exclusion criteria
X
X
Physical examination3
X
X
X
X
X
X
X
Medical history/current medical 
conditions
X
Concomitant medications
As required
Demography
X
Body height
X
Body weight
X
X
X
Body temperature
X
X
X
X 
X
X
X 
X
X 
X
Pulse rate
X
X
X
X
X
X
X
X
X
X
Blood pressure
X
X
X
X
X
X
X
X
X
X
ECG evaluation3
X
X
X
X
X
X
Blood chemistry
X
X
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
Urinalysis
X
X
X
X
X
X
X
X
X
X
Pregnancy test4
X
X
X
X
X
X
X
X
X
X
Hepatitis and HIV Screen
X
Tuberculosis test3
X
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Study Epoch
Screening
Treatment Period 1
Extension Period 2
Post-treatment 
Follow-up
Visit Numbers1
V1
V101
V102
V1032
V201
V202
V203
V2042
V30116
V3022,16
Study Day(s)
-28 to -2
1
+2
29
-5 +5
57
-5 +5
85
-5 +5
113
-5 +5
141
-5 +5
169
-3 +3
218
-10 +10
260
-15 +15
Time (post-dose)
-
-
-
-
-
-
-
-
-
-
Serious adverse events (SAEs)5
As required
Adverse events (AEs)
As required
Drug administration record
X
X
X
X
X
X
X
PK blood collection6
X
X
X
X
X
X
X
X
X
X
X
X
X
Facial inflammatory lesion counts7
X
X
X
X
X17
X
X
X
X
X
Facial non-inflammatory lesion count8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Facial and non-facial nodule count
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study completion information
X
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1 Visit structure given for internal programming purpose only
2 The end of each Epoch is marked by the completion of the disposition CRF (x99) in the summary CRF section...
3 Collected in source documentation only.
4 Blood test at screening and EOS or last visit; additional urine tests are done throughout the study if pregnancy is suspected (e.g. if subject experience irregular 
menstrual period). 
5 SAEs collected up to 30 days following the EOS Visit
6 Pre-dose sample on dosing days.
7 Papules, pustules and nodules
8 Open and closed comedones 
16 Visits to be completed by patients who discontinue from a treatment period early, or decide not to proceed to extension period 2 after participation in treatment period 1.  
17 Responder status will be assessed pre-dose.
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8.1
Informed consent procedures
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent.
Informed consent must be obtained before conducting any study-specific procedures (i.e. all 
of the procedures described in the protocol). The process of obtaining informed consent 
should be documented in the patient source documents.
The date of signing of informed consent (and withdrawal, if later withdrawn) should be 
documented in the CRF.
Novartis will provide to investigators a proposed informed consent form that complies with 
the ICHE6 GCP guideline and regulatory requirements and is considered appropriate for this 
study. The informed consent form will also include a section related to optional future 
research which will require a separate signature if the patient agrees to future research.  
Any changes to the proposed consent form suggested by the Investigator must be agreed to by 
Novartis before submission to the IRB/IEC.
Information about common side effects already known about the investigational drug can be 
found in the IB. This information will be included in the patient informed consent and should 
be discussed with the subject during the study as needed. Any new information regarding the 
safety profile of the investigational drug that is identified between IB updates will be 
communicated as appropriate, for example, via an Investigator Notification or an Aggregate 
Safety Finding. New information might require an update to the informed consent and then 
must be discussed with the patient.
Ensure patients are informed of the contraception requirements outlined in the Section 4.2
(Exclusion criteria) and in Section 5.1 (Contraception requirements).
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother.
In the event that Novartis wants to perform testing on the samples that are not described in
this protocol, additional IRB and/or IEC approval will be obtained.
A copy of the approved version of all consent forms must be provided to the Novartis monitor 
after IRB/IEC approval.
8.2
Subject screening
Information on what data should be collected for screening failures is outlined in the SOM. 
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8.3
Subject demographics/other baseline characteristics
Subject demographic and baseline characteristic data will be collected on all subjects.  
Relevant medical history/current medical conditions data will also be collected until signature 
of informed consent. Details are outlined in the SOM.
Investigators have the discretion to record abnormal test findings on the medical history CRF, 
if in their judgment, the test abnormality occurred prior to the informed consent signature.
8.4
Efficacy / Pharmacodynamics
Pharmacodynamic and efficacy assessments are specified below, with the methods for 
assessment and recording specified in the SOM. As clinical efficacy measures are rater 
dependent, each evaluator should be appropriately trained and qualified for these assessments. 
Every effort should be made that the same evaluator assesses and counts the lesions 
throughout the study.
Assessments will be performed and pharmacodynamic samples will be collected at the 
timepoints defined in the Assessment Schedule. Follow instructions outlined in the SOM
regarding sample collection, numbering, processing and shipment.
In order to better define the Pharmacodynamic (PD) profile, the timing of the sample 
collection may be altered based on emergent data. The number of samples/blood draws and 
total blood volume collected will not exceed those stated in the protocol.
PD samples will be obtained and evaluated in all subjects at all dose levels. 
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8.4.1.4
Patient-Reported Outcomes (PRO)
All PROs should be completed pre-dose on the dosing days. 
8.4.1.4.2 Patient global assessment
The patients will be asked at predefined visits, what their perception of efficacy and treatment 
satisfaction is. The question asked will be “How would you rate your acne today?” 
The following rating will be used:
Table 8-4
Patient Global Assessment
Grade
Rating
0
Clear
1
Minimal / Almost clear
2
Mild
3
Moderate
4
Severe
5
Very severe 
8.4.1.4.3 Patient's treatment satisfaction questionnaire
Patient’s treatment satisfaction questionnaire is to inform about the overall satisfaction from 
the patient's perspective.  The following questions will be asked at visits as specified in the 
Assessment Schedule:
1.
How satisfied or dissatisfied are you with this acne treatment?  
2 
Overall, and taking all things into account, how satisfied or dissatisfied are you with this 
medication? 
3 
Would you use this medication again if you were in the same condition as at the start of 
the trial? 
All above questions will be answered by using a 7 point Likert scale approach (question 1-3 
with extremes such as ‘Extremely Satisfied' to 'Extremely Dissatisfied').
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8.5
Safety
Safety assessments are specified below; methods for assessment and recording are specified in 
the SOM, with the Assessment Schedule detailing when each assessment is to be performed.
8.5.1
Physical examination
Physical examination will be done at timepoints specified in the Assessment Schedule.
8.5.2
Vital signs

Body temperature

Blood pressure (BP) 

Pulse 
8.5.3
Height and weight

Height

Body weight

Body mass index (BMI) will be calculated (Body weight (kg) / [Height (m)]2)
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8.5.4
Laboratory evaluations
Clinically relevant deviations of laboratory test results occurring during or at completion of 
the study must be reported and discussed with Novartis personnel. The results should be 
evaluated for criteria defining an adverse event and reported as such if the criteria are met. 
Repeated evaluations are mandatory until normalization of the result(s) or until the change is 
no longer clinically relevant. In case of doubt, Novartis personnel should again be contacted.
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential 
(e.g., neutrophils, basophils, eosinophils, monocytes, lymphocytes) and platelet count will be 
measured. Both absolute and differential cell counts will be recorded.
Clinical chemistry
Albumin, alkaline phosphatase, total bilirubin, calcium, cholesterol, chloride, creatinine, CK,
CRP, -GT, glucose, LDH, inorganic phosphorus, lipase, amylase, magnesium, potassium, 
total protein, AST, ALT, sodium, triglycerides, BUN and uric acid.
For postmenopausal women, FSH is measured at screening to assist in confirming 
menopausal status.
If the total bilirubin concentration is increased above 1.5 times the upper limit of normal, 
direct and indirect reacting bilirubin should be differentiated.
Urinalysis
A midstream urine sample (approx. 30 ml) will be obtained, in order to avoid contamination 
with epithelial cells and sediments, and allow proper assessments.
A semi-quantitative “dipstick” evaluation for the following parameters will be performed: 
specific gravity, pH, glucose, protein, bilirubin, ketones, nitrite, leukocytes and blood.
If the dipstick result is positive for protein, leucocytes and/or blood the sample will be sent for 
microscopic analysis of WBC, RBC and casts.
8.5.5
Electrocardiogram (ECG)
Standard 12-lead ECGs will be used to be performed at the visits specified in the 
Assessment Schedule. The preferred sequence of data collection during study visits is ECG 
collection first (10 min rest, ECG recording over next 5 min suggested), followed by vital 
signs (heart rate and BP), and PK sampling.  
The Fridericia QT correction formula (QTcF) should be used for clinical decisions.

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8.5.6
Pregnancy and assessments of fertility
All females (irrespectively of reproductive status) will need to have serum pregnancy test at 
screening and EOS.
All women who are not surgically sterile will have regular urine pregnancy tests during the 
study as outlined in the Assessment Schedule. Additional urine pregnancy tests may be 
required, if a reason occurs such as patient reports delay in menstruation. A positive urine 
pregnancy test requires immediate interruption of study drug until serum β-hCG is performed 
and found to be negative.
8.5.7
Tuberculosis test
Blood tuberculosis testing with the Quantiferon assay (QuantiFERON®-TB Gold In-Tube)
will be performed as specified in the Assessment Schedule.
8.6
Pharmacokinetics
PK samples (total CJM112) will be collected at the time points defined in the 
Assessment Schedule. Follow instructions outlined in the SOM regarding sample collection, 
numbering, processing and shipment, see Section 8.8.
Samples will be analyzed as per laboratory’s standard operating procedures, and total 
CJM112 in serum will be determined by a validated ELISA method. The anticipated Lower 
Limit of Quantification (LLOQ) is 240 ng/mL in 100% human serum. All procedures and 
analytical methods will be detailed in the bioanalytical data report.
Pharmacokinetic (PK) samples will be obtained and evaluated in all subjects at all dose levels. 
Concentrations will be expressed in microg/mL, the time unit is day. Concentrations below 
the LLOQ will be reported as “zero” and missing data will be labeled as such in the 
Bioanalytical Data Report.
8.7
Other assessments
No additional tests will be performed on subjects entered into this study.
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9
Safety monitoring
9.1
Adverse events
An AE is any untoward medical occurrence (i.e., any unfavorable and unintended sign 
[including abnormal laboratory findings], symptom or disease) in a subject or clinical 
investigation subject after providing written informed consent for participation in the study 
until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product.
In addition, all reports of intentional misuse and abuse of the study treatment are also 
considered an AE irrespective if a clinical event has occurred. See Section 9.5 for an overview 
of the reporting requirements.
The occurrence of AEs must be sought by non-directive questioning of the patient at each 
visit during the study. AEs also may be detected when they are volunteered by the patient 
during or between visits or through physical examination finding, laboratory test finding, or 
other assessments.
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria:

they induce clinical signs or symptoms,

they are considered clinically significant,

they require therapy.
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patients with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying AEs. Alert ranges for liver and kidney related events are included in 
Appendix 1 and Appendix 2, respectively.
For patients that pass screening and enter in the study, AEs must be recorded on the AEs CRF 
under the signs, symptoms or diagnosis associated with them, and accompanied by the 
following information:
1. the severity grade 

mild: usually transient in nature and generally not interfering with normal activities

moderate: sufficiently discomforting to interfere with normal activities

severe: prevents normal activities
2. its relationship to the study treatment (no/yes), or investigational treatment (no/yes), or 
other study treatment (non-investigational) (no/yes), or both or indistinguishable,
3. its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported.
4. whether it constitutes a SAE (see Section 9.2 for definition of SAE) and which seriousness 
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5. Action taken regarding investigational treatment.
All AEs must be treated appropriately. Treatment may include one or more of the 
following:

no action taken (e.g. further observation only)

investigational treatment dosage increased/reduced

investigational treatment interrupted/withdrawn

concomitant medication or non-drug therapy given

hospitalization/prolonged hospitalization (see Section 9.2 for definition of SAE)  
6. its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown)
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the investigational drug, the 
interventions required to treat it, and the outcome.
Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB) or will be communicated between IB updates in the 
form of Investigator Notifications. This information will be included in the subject informed 
consent and should be discussed with the subject during the study as needed.
The investigator must also instruct each subject to report any new AE (beyond the protocol 
observation period) that the subject, or the subject’s personal physician, believes might 
reasonably be related to study treatment. This information must be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.
9.2
Serious adverse event reporting
9.2.1
Definition of SAE
An SAE is defined as any AE (appearance of (or worsening of any pre-existing) undesirable 
sign(s), symptom(s) or medical conditions(s)) which meets any one of the following criteria:

is fatal or life-threatening

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 

routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 

elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since the start of study drug

treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission

social reasons and respite care in the absence of any deterioration in the subject’s 
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
is medically significant, e.g. defined as an event that jeopardizes the subject or may 
require medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the subject was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (see Annex IV, ICH-E2D Guideline).
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
subject or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (see Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All AEs (serious and non-serious) are captured on the CRF; SAEs also require individual 
reporting to Novartis DS&E as per Section 9.2.2.
9.2.2
SAE reporting
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 30 days after the last study visit must be reported to 
Novartis within 24 hours of learning of its occurrence as described below. Any SAEs 
experienced after this period should only be reported to Novartis if the investigator suspects a 
causal relationship to study treatment.
Note: SAEs reported by subjects deemed to be screen failures must be reported to Novartis as 
outlined here with appropriate information also captured in the CRFs as specified in the SOM.
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at 
a different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event.
Follow- up information provided must describe whether the event has resolved or continues, if 
and how it was treated, whether the blind was broken or not (if applicable) and whether the 
subject continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event must be reported as a follow-up to that event regardless of 
when it occurs.
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment a Drug Safety and Epidemiology Department 
associate may urgently require further information from the investigator for Health Authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 

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reported. Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and 
reported to the competent authorities and relevant ethics committees in accordance with EU 
Guidance 2011/C 172/01 or as per national regulatory requirements in participating countries.
Follow the detailed instructions outlined in the SOM regarding the submission process for 
reporting SAEs to Novartis.   Note:  SAEs must be reported to Novartis within 24 hours of 
the investigator learning of its occurrence/receiving follow-up information.
9.3
Liver safety monitoring
To ensure subject safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed.
Please refer to Table 15-1-Appendix 1 for complete definitions of liver events.
Follow-up of liver events
Every liver event defined in Table 15-1-Appendix 1 should be followed up by the investigator 
or designated personnel at the trial site, as summarized below. Additional details on actions 
required in case of liver events are outlined in Table 15-2-Appendix 1. 

Repeating liver chemistry tests (ALT, AST, TBL, PT/INR, ALP and γGT) to confirm 
elevation within 48-72 hours.  
These liver chemistry repeats should be performed using the central laboratory if possible, 
with the results provided via the standard electronic transfer.  If results will not be 
available from the central laboratory within 24 hours, then the repeats can also be 
performed at a local laboratory to monitor the safety of the subject. If a liver event is 
subsequently reported, any local liver chemistry tests previously conducted that are 
associated with this event should have results reported on the unscheduled local laboratory 
CRF.  

If the initial elevation is confirmed, close observation of the subject will be initiated, 
including consideration of treatment interruption if deemed appropriate.

Discontinuation of the investigational drug (refer to Section 7.2 (Discontinuation of study 
treatment), if appropriate

Hospitalization of the subject if appropriate

Causality assessment of the liver event

Thorough follow-up of the liver event should include: 

Repeating liver chemistry tests two or three times weekly. Testing should include 
ALT, AST, ALP, PT/INR, and γGT. If total bilirubin is elevated > 2 x ULN, 
fractionation into direct and indirect bilirubin is required. To rule out muscular origin 
of transaminase elevations, Creatinine Phosphokinase (CPK) should be measured 
along with liver chemistry tests. Frequency of retesting can decrease to once a week 
or less if abnormalities stabilize or the study drug has been discontinued and the 
subject is asymptomatic. Retesting should be continued up to resolution. 

Obtaining a more detailed history of symptoms and prior or concurrent diseases.

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
Obtaining a history of concomitant drug use (including nonprescription medications 
and herbal and dietary supplement preparations), alcohol use, recreational drug use, 
and special diets.

Exclusion of underlying liver disease, as specified in Table 15-3.

Imaging such as abdominal US, CT or Magnetic resonance imaging (MRI), as 
appropriate

Obtaining a history of exposure to environmental chemical agents.

Considering gastroenterology or hepatology consultations.
All follow-up information, and the procedures performed must be recorded as appropriate in 
the CRF.
9.4
Renal safety monitoring
Every renal laboratory trigger or renal event must be followed up by the investigator or 
designated personnel at the trial site. Recommended follow-up assessments are listed in 
Section 16 -Appendix 2.
Renal events are defined as one of the following:

confirmed (after ≥ 24h) increase in serum creatinine of ≥ 25% compared to baseline 
during normal hydration status

new onset (≥1+) proteinuria, hematuria or glucosuria; or as a

doubling in the urinary albumin-creatinine ratio (ACR) or urinary protein-creatinine ratio 
(PCR) (if applicable).
The following two categories of abnormalities/AEs have to be considered during the course of 
the study:

Serum creatinine triggers that will require follow up and repeat assessments of the 
abnormal laboratory parameter

Urine dipstick triggers that will require follow up and repeat assessments of the abnormal 
laboratory parameter
9.5
Reporting Medication errors including misuse/abuse
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient/subject 
or consumer (EMA definition).
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects.
All study treatment errors and uses outside of what is foreseen in the protocol will be 
collected in the dose administration record (DAR) CRF.  Study treatment errors are only to be 
reported to Novartis DS&E department if the treatment error is associated with an SAE.

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All instances of misuse or abuse must be documented in the AE CRF irrespective of the 
misuse/abuse being associated with an AE/SAE. In addition, all instances of misuse or abuse 
must be reported to Novartis Drug Safety and Epidemiology. As such, instances of misuse or 
abuse are also to be reported using the SAE form/CRF. Table 9-1 summarizes the reporting 
requirements.
Table 9-1
Summary of reporting requirements for medication errors
Treatment error type
Document in Dose 
Administration (DAR) CRF
Document in AE 
CRF
Complete SAE 
form/CRF
Unintentional study 
treatment error
Yes
Only if associated 
with an AE
Only if associated with 
an SAE
Misuse/Abuse
Yes
Yes
Yes, even if not 
associated with a SAE
For more information on AE and SAE definition and reporting requirements, 
please see Section 9.1 and Section 9.2, respectively.
9.6
Pregnancy reporting
To ensure subject safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should 
be followed up to determine outcome, including spontaneous or voluntary termination, details 
of the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications.
Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis DS&E Department. Pregnancy follow-up should be recorded 
on the same form and should include an assessment of the possible relationship to the study 
treatment.
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.
The study drug must be discontinued, though the subject may stay in the study, if she wishes 
to do so. All assessments that are considered as a risk during pregnancy must not be 
performed. The subject may continue all other protocol assessments.
Pregnancy outcomes should be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother. 
9.7
Early phase safety monitoring
The Investigator will monitor AEs in an ongoing manner and inform the Sponsor of any 
clinically relevant observations. Any required safety reviews will be made jointly between 
medically qualified personnel representing the Sponsor and Investigator. Such evaluations 
may occur verbally, but the outcome and key discussion points will be summarized in writing 
(e-mail) and made available to both Sponsor and all Investigator(s). Criteria pertaining to 
stopping the study/treatment or adapting the study design are presented above.

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When two or more clinical site(s) are participating in the clinical study, the Sponsor will 
advise the Investigator(s) at all sites in writing (e-mail) (and by telephone if possible) of any 
new, clinically relevant safety information reported from another site during the conduct of 
the study in a timely manner.
10
Data review and database management
10.1
Site monitoring
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and CRFs with the investigators and their staff. 
During the study Novartis employs several methods of ensuring protocol and GCP 
compliance and the quality/integrity of the sites’ data. The monitor will visit the site to check 
the completeness of subject records, the accuracy of entries on the CRFs, the adherence to the 
protocol and to Good Clinical Practice, the progress of enrollment, and ensure that study drug 
is being stored, dispensed, and accounted for according to specifications. Key study personnel 
must be available to assist the monitor during these visits.
Continuous remote monitoring of each site’s data may be performed by Novartis. 
Additionally, a central analytics organization may analyze data and identify risks & trends for 
site operational parameters, and provide reports to Novartis Clinical Teams to assist with trial 
oversight.
The investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. 
All information on CRFs must be traceable to these source documents in the subject's file. 
The investigator must also keep the original informed consent form signed by the subject 
(a signed copy is given to the subject).
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Novartis monitoring standards require full verification 
for the presence of informed consent, adherence to the eligibility criteria, documentation of 
SAEs, and the recording of data that will be used for all primary and safety variables. 
Additional checks of the consistency of the source data with the CRFs are performed 
according to the study-specific monitoring plan. No information in source documents about 
the identity of the subjects will be disclosed.
10.2
Data collection
Designated investigator staff will enter the data required by the protocol into the eCRF using 
fully 
validated 
software 
that 
conforms 
to 
21 
CFR 
Part 
11 
requirements. 
Designated investigator site staff will not be given access to the EDC system until they have 
been trained. Automatic validation programs check for data discrepancies and, by generating 
appropriate error messages, allow the data to be confirmed or corrected before transfer of the 
data to the CRO working on behalf of Novartis. The Investigator must certify that the data 
entered into the eCRFs are complete and accurate. After database lock, the investigator will 
receive copies of the subject data for archiving at the investigational site.

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Data not requiring a separate written record will be defined in the SOM
and 
Assessment Schedule and can be recorded directly on the CRFs. All other data captured for 
this study will have an external originating source (either written or electronic) with the CRF 
not being considered as source.
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification.
10.3
Database management and quality control
CRO working on behalf of Novartis review the data entered into the CRFs by investigational 
staff for completeness and accuracy and instruct the site personnel to make any required 
corrections or additions. Queries are sent to the investigational site using an electronic data 
query. Designated investigator site staff is required to respond to the query and confirm or 
correct the data. If the electronic query system is not used, a paper Data Query Form will be 
faxed to the site. Site personnel will complete and sign the faxed copy and fax it back to CRO 
working on behalf of Novartis who will make the correction to the database. The signed copy
of the Data Query Form is kept at the investigator site.
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Medical history/current medical conditions and AEs will be coded using the Medical 
dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to a 
designated CRO.
Randomization codes and data about all study drug(s) dispensed to the subject and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The database will be sent 
electronically to Novartis (or a designated CRO).
At the conclusion of the study, the occurrence of any emergency code breaks will be 
determined after return of all code break reports and unused drug supplies to Novartis.
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. 
The code break functionality will remain available until study shut down or upon request of 
Novartis.
The occurrence of any protocol deviations (PD) will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. 
Any changes to the database after that time can only be made by joint written agreement 
between the Clinical Operations, Analytics & Regions (COAR) Analytics Novartis Institute of 
Biomedical Research (NIBR) Franchise Head and the relevant NIBR Therapeutic Area Head.
To maximize confidentiality, all samples will be double-coded to prevent the exposure of the 
subject’s identity. This double-coding process allows Novartis to go back and destroy the 
sample at the subject’s request. In addition, sample information is stored in one secured 
database while genetic data is stored in an independent secured database.

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10.4
Data Monitoring Committee
Not required.
10.5
Adjudication Committee
Not required.
11
Data analysis
The analyses will be conducted on all subject data at the time when interim analysis occurs 
and also when the trial ends. Any data analysis carried out independently by the investigator 
should be submitted to Novartis before publication or presentation.
11.1
Analysis sets
For all analysis sets, subjects will be analyzed according to the study treatment(s) received.
The safety analysis set will include all subjects that received any study drug.
The PK analysis set will include all subjects with at least one available valid (i.e. not flagged 
for exclusion) PK concentration measurement, who received any study drug and with no 
protocol deviations that impact on PK data.
The PD analysis set will include all subjects with available PD data and no protocol 
deviations with relevant impact on PD data.
11.2
Subject demographics and other baseline characteristics
All data for background and demographic variables will be listed by treatment group and 
subject. Summary statistics will be provided by treatment group. Subject demographics will 
include age, sex, race, ethnicity, country, height, weight and BMI. Baseline disease 
characteristics include but are not limited to: inflammatory facial lesion count and IGA.
Relevant medical history, current medical conditions, results of laboratory screens, drug tests 
and any other relevant information will be listed by treatment group and subject.
11.3
Treatments
Data for study drug administration (rescue medication) and concomitant therapies will be 
listed by treatment group and subject.
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11.4
Analysis of the primary variable(s)
The primary aim of this study is to assess the efficacy of CJM112 versus placebo on 
inflammatory facial lesion counts in patients with moderate to severe inflammatory acne. 
Therefore, a statistical analysis will be performed on the log transformed inflammatory facial 
lesion count after 12 weeks. Details are provided in Section 11.4.2.
11.4.1
Variable(s)
The primary variable is the natural log transformed total inflammatory facial lesion counts at 
Week 12.
11.4.2
Statistical model, hypothesis, and method of analysis
The log transformed inflammatory facial lesion count is expected to be approximately 
normally distributed. It will be analyzed using a Bayesian mixed effect model for repeated 
measures (MMRM), with log transformed baseline inflammatory facial lesion count as a 
covariate; treatment sequence, visit, treatment group by visit interaction and log transformed 
baseline inflammatory facial lesion count by visit interaction as fixed effects. A non-
informative prior will be utilized to obtain the posterior estimates. Unstructured covariance 
structure will be used. Other factors such as gender and race will also be explored for 
statistical significance if the distribution per factor is reasonably balanced. The log 
transformed baseline lesion count will be centered and standardized before used in the model.
Data up to Week 12 will be included in the model, for the comparison of CJM112 
 
versus placebo at Week 12, which is of primary interest. 
 
 
 
Bayesian posterior probabilities will be used to assess the following criteria as a guide to 
decision making (Fisch et al 2015), though other criteria may be taken into account:
 
 
 
 
 
The posterior estimates of the treatment effect and the treatment difference (along with its 
90% credibility interval) at each visit (with Week 12 being of primary interest) will be 
provided. The results will be reported in terms of ratio of geometric means by back 
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transforming the estimates from the log-scale. Data will also be presented in graphics such as 
spaghetti plot.
11.4.3
Handling of missing values/censoring/discontinuations
All patients with available data after baseline and until Week 12 will be included in the 
primary analysis. The primary analysis model is known to give unbiased results under the 
assumption that missing data are at random (MAR), i.e. given observed data the missingness 
does not depend on unobserved data. If a patient drops out the study according to the 
predefined discontinuation criteria (Section 7.2), this MAR assumption remains valid. Besides, 
last observation carried forward (LOCF) method will be used in a sensitivity analysis to 
handle missing data.
11.4.4
Sensitivity analyses
A negative binomial or Poisson generalized linear model on facial inflammatory lesion count 
at Week 12 will be applied as a sensitivity analysis. Baseline lesion count will be used as a 
covariate and treatment group as a factor. 
11.5
Analysis of secondary variable(s)
11.5.1
Safety
Vital signs
All vital signs data will be listed by treatment group, subject, and visit/time and if ranges are 
available abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics 
will be provided by treatment and visit/time.
ECG evaluations
All ECG data will be listed by treatment group, subject and visit/time, abnormalities will be 
flagged. Summary statistics will be provided by period, treatment and visit/time.
Clinical laboratory evaluations
All laboratory data will be listed by treatment group, subject, and visit/time and if normal 
ranges are available abnormalities will be flagged. Summary statistics will be provided by 
period, treatment and visit/time.
Adverse Events (AEs)
All information obtained on AEs will be displayed by treatment group and subject.
The number and percentage of subjects with AEs will be tabulated by body system and 
preferred term with a breakdown by period and treatment. A subject with multiple AEs within 
a body system is only counted once towards the total of this body system. 

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Other safety evaluations
Pregnancy test results will be listed by treatment group, subject and visit/time.
11.5.2
Pharmacokinetics
Total CJM112 serum concentration data (in microg/mL) will be listed by treatment group, 
subject, and visit/sampling time point. Descriptive summary statistics will be provided by 
treatment and visit/sampling time point, including the frequency (n, %) of concentrations 
below the LLOQ and reported as zero. Summary statistics will include mean (arithmetic and 
geometric), SD, CV (arithmetic and geometric), median, minimum and maximum. 
Concentrations below LLOQ will be treated as zero in summary statistics and for PK 
parameter calculations. A geometric mean will not be reported if the dataset includes zero 
values.
Pharmacokinetic parameters will be calculated as described in Section 8.6 and will be listed 
by treatment and subject. Summary statistics will include mean (arithmetic and geometric), 
SD, CV (arithmetic and geometric), median, minimum and maximum. A geometric mean will 
not be reported if the dataset includes zero values.
11.5.3
Pharmacokinetic / pharmacodynamic interactions
Not Applicable.
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11.7
Sample size calculation
A total number of 75 patients with
a 1:1:1 randomization ratio should provide around 
21 patients in each treatment group with complete 12-week data, assuming a dropout rate of 
around 15%.
 
 
 
 
The 30% difference in total inflammatory facial lesion count at Week 12 between a standard 
care oral antibiotics and placebo, reported by Fleischer et al 2006, served as reference to 
define a more stringent threshold of at least 40% difference to placebo for the sample size 
calculation. Assuming a geometric mean of 20 lesions in the placebo group at Week 12, the 
30% difference (a delta of 0.357 on the log scale) corresponds to approximately 6 lesions 
difference in geometric means; a 40% difference (a delta of 0.511 on the log scale) 
corresponds to approximately 8 lesions difference in geometric means. 
 
 
 
 
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Table 11-1
Operating characteristics of decision rules for n=21 per arm
Sample size
True effect = 0%
True effect = 40%
Chance of 
meeting efficacy 
criteria
(Type I error)
Chance of 
meeting futility 
criterion
Chance of 
meeting efficacy 
criteria
(Power)
Chance of 
meeting futility 
criterion
(Type II error)
10+10 (IA1)
5%
40%
77%
< 1%
21+21 (IA2)
5%
-
90%
-
Note: Calculations assume a SD of 0.47 of log-transformed inflammatory facial lesion count and an 
effect of 40% over placebo is considered a good effect.
Figure 11-1
Operating characteristics curve for n=21 per arm
11.8
Power for analysis of key secondary variables
Not applicable.
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12
Ethical considerations
12.1
Regulatory and ethical compliance
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations (including European Directive 2001/20/EC, US Code of Federal 
Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the 
ethical principles laid down in the Declaration of Helsinki.
12.2
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the IRB/IEC for the trial protocol, written informed consent form, consent form updates, 
subject recruitment procedures (e.g. advertisements) and any other written information to be 
provided to subjects. Prior to study start, the investigator is required to sign a protocol 
signature page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give access 
to all relevant data and records to Novartis monitors, auditors, Novartis Quality Assurance 
representatives, designated agents of Novartis, IRBs/IECs, and regulatory authorities as 
required. If an inspection of the clinical site is requested by a regulatory authority, the 
investigator must inform Novartis immediately that this request has been made.
For multi-center trials, a Coordinating Investigator will be selected by Novartis around the 
time of Last Patient Last Visit to be a reviewer and signatory for the clinical study report. 
12.3
Publication of study protocol and results
The key design elements of this protocol will be posted in a publicly accessible database such
as clinicaltrials.gov. In addition, upon study completion and finalization of the study report 
the results of this trial will be either submitted for publication and/or posted in a publicly 
accessible database of clinical trial results.
13
Protocol adherence
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs under the protocol.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented.

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13.1
Protocol Amendments
Any change to the protocol can only be made in a written protocol amendment that must be 
approved by Novartis, Health Authorities where required, and the IRB/IEC prior to 
implementation.
Amendments that are intended to eliminate an apparent immediate hazard to subjects may be 
implemented immediately, provided the Health Authorities are subsequently notified by 
protocol amendment and the reviewing IRB/IEC is notified.
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting
requirements identified in Section 9 (Safety Monitoring) must be followed and the Study Lead 
informed.

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14
References
Available upon request
Agak GW, Qin M, Nobe J, et al (2014) Propionibacterium acnes Induces an IL-17 Response 
in Acne Vulgaris that Is Regulated by Vitamin A and Vitamin D. J. Invest. Dermatol.; 
134:366-73.
Borovaya A, Dombrowski Y, Zwicker S, et al (2014) Isotretinoin therapy changes the 
expression of antimicrobial peptides in acne vulgaris. Arch. Dermatol. Res.;306:689-700.
CDER (2005) US Department of Health and Human Services, Public Health Service, Food 
and Drug Administration Guidance for Industry; Acne Vulgaris: Developing Drugs Treatment. 
Draft guidance. Rockville, MD 
ClinicalTrial.gov, NCT01498874 (2011) Efficacy and Safety Study of Gevokizumab to Treat 
Moderate to Severe Acne Vulgaris (Internet) Available from: 
<https://clinicaltrials.gov/ct2/show/NCT01498874> (Accessed 20 June 2016)  
ClinicalTrial.gov, NCT02320149 (2014)  Study to Evaluate Safety & Efficacy of Sarecycline 
in Treatment of Acne (Internet) Available from:  
<https://clinicaltrials.gov/ct2/show/NCT02320149> (Accessed 20 June 2016) 
ClinicalTrial.gov, NCT02322866 (2014) Randomized, Double-blind, Placebo-controlled 
Study to Evaluate Safety & Efficacy of Sarecycline in Treatment of Acne (Internet) Available 
from: <https://clinicaltrials.gov/ct2/show/NCT02322866> (Accessed 20 June 2016) 
ClinicalTrial.gov, NCT02471144 (2015) Pediatric Study in Children and Adolescents With 
Severe Plaque Psoriasis (Internet) Available from: <https://clinicaltrials.gov/ct2/show/ 
NCT02471144> (Accessed 20 June 2016)
ClinicaTtrial.gov, NCT01474798 (2011) Phase II Trial of RA-18C3 in Subjects With 
Moderate to Severe Acne Vulgaris (Internet) Available from: 
<https://clinicaltrials.gov/ct2/show/NCT01474798> (Accessed 20 June 2016) 
Das S, Reynolds RV (2014) Recent advances in acne pathogenesis: implications for therapy. 
Am J Clin Dermatol;15:479-88.
Finlay AY, Khan GK (1994) Dermatology Life Quality Index (DLQI)-a simple practical 
measure for routine clinical use. Clin. Exp. Dermatol.;19:210-6.
Fleischer AB, Dinehart S, Stough D, et al (2006) Safety and efficacy of a new extended-
release formulation of minocycline. Cutis;78 (Suppl.4):21-31.
Fisch R, Jones I, Jones J, et al (2015) Bayesian Design of Proof-of-Concept Trials. 
Therapeutic Innovation & Regulatory Science; 49: 155-162.
Halvorsen JA, Stern RS, Dalgard F, et al (2011) Suicidal ideation, mental health problems, 
and social impairment are increased in adolescents with acne: a population-based study. 
J. Invest. Dermatol.;131:363-70.

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Hueber W, Sands BE, Lewitzky S, et al (2012) Secukinumab, a human anti-IL-17A 
monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a 
randomised, double-blind placebo-controlled trial. Gut;61:1693-700.
Karadag AS, Ertugrul DT, Bilgili SG, et al (2012) Immunoregulatory effects of isotretinoin in 
patients with acne. Br. J. Dermatol.;167:433-5.
Kelhälä HL, Palatsi R, Fyhrquist N, et al (2014) IL-17/Th17 pathway is activated in acne 
lesions. PLoS ONE 9(8): e105238.
Kurd SK, Troxel AB, Crits-Christoph P, et al (2010) The Risk of Depression, Anxiety, and 
Suicidality in Patients With Psoriasis. Arch Dermatol;146(8):891-895.
Lee JW, Yoo KH, Park KY, et al (2011) Effectiveness of conventional, low-dose and 
intermittent oral isotretinoin in the treatment of acne: a randomized, controlled comparative 
study. Br J Dermatol;164(6):1369-75. 
Lucky AW, Henderson TA, Olson WH, et al (1997) Effectiveness of norgestimate and ethinyl 
estradiol in treating moderate acne vulgaris. J Am Acad Dermatol.;37(5 Pt 1):746-54.
Picardi A, Lega I, Tarolla E (2013) Suicide risk in skin disorders. Clinics in Dermatology; 31: 
47–56.
Purvis D, Robinson E, Merry S, et al (2006) Acne, anxiety, depression and suicide in 
teenagers: a cross-sectional survey of New Zealand secondary school students. J Paediatr 
Child Health;42:793-6.
Silverberg JI, Silverberg NB (2014) Epidemiology and extracutaneous comorbidities of 
severe acne in adolescence: a U.S. population-based study. Br. J. Dermatol.; 179: 1136-42.
Tan JK, Tang J, Fung K, et al (2007) Development and validation of a comprehensive acne 
severity scale. J Cutan Med Surg;11(6):211-6.
Thiboutot D, Gollnick H, Bettoli V, et al (2009) New insights into the management of acne: 
an update from the Global Alliance to Improve Outcomes in Acne group. J Am Acad 
Dermatol.;60(5 Suppl):S1-50

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15
Appendix 1: Liver Event Definitions and Follow-up 
Requirements
Table 15-1
Liver Event Definitions
Definition
Thresholds
Potential Hy’s law cases

ALT or AST > 3 × ULN and TBL > 2 × ULN without initial increase 
in ALP to > 2 × ULN
ALT or AST elevation with 
coagulopathy

ALT or AST > 3 × ULN and INR > 1.5 (in the absence of 
anticoagulation)
ALT or AST elevation 
accompanied by symptoms

ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash, or eosinophilia
Isolated ALT or AST elevation

ALT or AST > 8 × ULN

5 x ULN < ALT/AST £ 8 x ULN

3 x ULN < ALT/AST £ 5 x ULN
Isolated ALP elevation

ALP > 2 × ULN (in the absence of known bone pathology)
Others

Any clinical event of jaundice (or equivalent term)

Any AE potentially indicative of liver toxicity
Table 15-2
Actions required for Liver Events
Criteria
Actions required
Potential Hy’s Law case

Discontinue the study treatment immediately

Hospitalize, if clinically appropriate

Establish causality

Complete CRFs per liver event guidance
ALT or AST elevation with coagulopathy
ALT or AST elevation accompanied by 
symptoms
Isolated ALT or AST elevation > 8 × ULN
Jaundice
Isolated ALT or AST elevation > 5 to ≤ 8 × 
ULN

If confirmed, consider interruption or discontinuation of 
study drug

If elevation persists for more than 2 weeks, 
discontinue the study drug

Establish causality

Complete CRFs per liver event guidance
Isolated ALT or AST elevation > 3 to ≤ 5 × 
ULN (patient is asymptomatic)

Monitor liver chemistry tests two or three times weekly
Isolated ALP elevation

Repeat liver chemistry tests within 48-72 hours

If elevation is confirmed, measure fractionated ALP; if 
>50% is of liver origin, establish hepatic causality

Complete CRFs per liver event guidance

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Criteria
Actions required
Any AE potentially indicative of liver 
toxicity

Consider study treatment interruption or
discontinuation

Hospitalize if clinically appropriate

Complete CRFs per liver event guidance
Table 15-3
Exclusion of underlying liver disease
Disease
Assessment
Hepatitis A, B, C, E

IgM anti-HAV; HBSAg, IgM anti-HBc, HBV DNA; anti-HCV, HCV RNA, 
IgM & IgG anti-HEV, HEV RNA
CMV, HSV, EBV 
infection

IgM & IgG anti-CMV, IgM & IgG anti-HSV; IgM & IgG anti-EBV
Autoimmune hepatitis

ANA & ASMA titers, total IgM, IgG, IgE, IgA
Alcoholic hepatitis

Ethanol history, γ GT, MCV, CD-transferrin
Nonalcoholic 
steatohepatitis

Ultrasound or MRI
Hypoxic/ischemic 
hepatopathy

Medical history: acute or chronic CHF, hypotension, hypoxia, hepatic 
venous occlusion. Ultrasound or MRI.
Biliary tract disease

Ultrasound or MRI, ERCP as appropriate.
Wilson disease

Caeruloplasmin
Hemochromatosis

Ferritin, transferrin
Alpha-1-antitrypsin 
deficiency

Alpha-1-antitrypsin

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16
Appendix 2: Specific Renal Alert Criteria and Actions
Table 16-1
Specific Renal Alert Criteria and Actions
Criteria
Action required
Serum creatinine (sCr) increase
25 – 49% compared to baseline

Consider causes and possible interventions

Follow up within 2-5 days
Serum creatinine increase > 50%

Consider causes and possible interventions

Repeat assessment within 24-48h if possible

Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected

Consider hospitalization and specialized 
treatment
Protein-creatinine or albumin-creatinine ratio 
increase ≥ 2-fold
or
new onset dipstick proteinuria ≥ 1+
or
Albumin-creatinine ratio (ACR) ≥ 30 mg/g or ≥ 
3 mg/mmol;
or
Protein-creatinine ratio (PCR )≥ 150 mg/g or 
>15 mg/mmol

Consider causes and possible interventions

Assess serum albumin & serum protein

Repeat assessment to confirm

Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected
New onset glucosuria on urine dipstick (unless 
related to concomitant treatment, diabetes)
Assess & document:

Blood glucose (fasting)

Serum creatinine

Urine albumin-creatinine ratio
New hematuria on dipstick
Assess & document:

Urine sediment microscopy

Assess sCr and urine albumin-creatinine ratio

Exclude infection, trauma, bleeding from the 
distal urinary tract/bladder, menstruation

Consider bleeding disorder
Additional specialized assessments are available to assess renal function or renal pathology. 
(Note: In exceptional cases when a nephrologist considers a renal biopsy, it is strongly 
recommended to make specimen slides available for evaluation by Novartis to potentially 
identify project-wide patterns of nephrotoxicity.)

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Whenever a renal event is identified, a detailed subject history and examination are indicated 
to identify, document and potentially eliminate risk factors that may have initiated or 
contributed to the event:

Blood pressure assessment (after 5 min rest, with an appropriate cuff size)

Signs and symptoms such as fever, headache, shortness of breath, back or abdominal pain, 
dysuria, hematuria, dependent or periorbital edema

Changes in blood pressure, body weight, fluid intake, voiding pattern, or urine output

Concomitant events or procedures such as trauma, surgical procedures, cardiac or hepatic 
failure, contrast media or other known nephrotoxin administration, or other potential 
causes of renal dysfunction, e.g., dehydration, hemorrhage, tumor lysis
Table 16-2
Follow-up of renal events
Action
Follow up
Assess*, document and record in the Case 
Report Form (CRF) or via electronic data load. 
Review and record possible contributing factors to 
the renal event (co-medications, other co-morbid 
conditions) and additional diagnostic procedures 
(MRI etc) in the CRF.

Urine dipstick and sediment microscopy

Blood pressure and body weight

Serum creatinine, electrolytes (sodium, 
potassium, phosphate, calcium), bicarbonate 
and uric acid

Urine output
Monitor subject regularly (frequency at 
investigator’s discretion) until:

Event resolution: (sCr within 10% of baseline 
or protein-creatinine ratio within 50% of 
baseline)
or

Event stabilization: sCr level with ±10% 
variability over last 6 months or protein-
creatinine ratio stabilization at a new level 
with ±50% variability over last 6 months.
* Urine osmolality: in the absence of diuretics or chronic kidney disease this can be a very 
sensitive metric for integrated kidney function that requires excellent tubular function. A high 
urinary osmolality in the setting of an increase in sCr will point toward a “pre-renal” cause 
rather than tubular toxicity.