Clinical trial NCT03467412
Conditions: Androgenic Alopecia
Sponsor: Follicum AB
Start date: 2018-02-27; Completion date: 2018-08-22
Enrollment: 60 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The trial was a multicentre, randomised, double-blind, placebo controlled phase 2 trial.

60 healthy bald male subjects diagnosed with alopecia, who are between 18 and 55 years old and provide written informed consent were eligible for inclusion.

The trial period consisted of a screening period of up to 3 weeks followed by 12 weeks of dosing, three times per week. Each subject received two doses of the five trial treatment doses (placebo, 0.00625, 0.025, 0.050, and 0.100 μg respectively). The doses were given as intradermal injections. On each volunteer, two treatment areas were placed on the head and the two selected doses were allocated to the respective treatment areas according to the randomisation scheme. The treatment areas were selected on the border between the bald surface and the surface with hair.

The effect on hair growth was measured by the use of Trichoscan imaging and measuring method at week 8 and 12. A baseline measaure was taken at day 0.

Detailed description:

Arms: arm 1: 50 μl solution (a total dose of 0.00625 μg FOL-005) injected intradermally three times per week for 12 weeks. arm 2: 50 μl solution (a total dose of 0.025 μg FOL-005) injected intradermally three times per week for 12 weeks. arm 3: 50 μl solution (a total dose of 0.050 μg FOL-005) injected intradermally three times per week for 12 weeks. arm 4: 50 μl solution (a total dose of 0.100 μg FOL-005) injected intradermally three times per week for 12 weeks. arm 5: 50 μl solution (placebo) injected intradermally three times per week for 12 weeks.
Interventions: intervention 1: FOL-005 intervention 2: Placebo
Intervention descriptions: intervention 1: intradermal injection intervention 2: intradermal injection

Protocol documents:
Prot_SAP_000.pdf: 
         
 
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CONFIDENTIAL 
CLINICAL TRIAL PROTOCOL 
 
 
A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to 
investigate efficacy on hair growth on scalp skin in healthy volunteers 
Trial code: 
FCS-002 
Trial development 
phase: 
Phase 2 
EudraCT number: 2017-003809-17 
Investigational 
medicinal product: 
FOL-005 solution for 
injection 
Version: 
1.0 
Date: 
07 November 2017 
 
 
 
 
 
Coordinating Investigator: 
Prof. Dr. Ulrike Blume-Peytavi 
 Sponsor Signatory: 
Jan Alenfall, PhD, CEO 
 
 
 
 
 
 
 
 
This document contains confidential information. The contents may not be used, divulged or published 
without prior written consent of Follicum AB.  
This information cannot be used for any other purpose than the conduct and evaluation of the clinical 
investigation by the investigator(s), the regulatory authorities and members of the ethics committees 
 


Sponsor: Follicum AB 
 
Clinical Trial Protocol 
Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
Final 
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07 November 2017 
 
 
Name of Company: 
 
 
Name of Active Ingredient: 
 
Individual trial table 
(For national authority use only) 
Name of Investigational Products: FOL-005 
• 
Solution for injection 
• 
Placebo solution for injection 
 
Trial under an IND:  
No 
Title of trial:  
A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to investigate efficacy 
on hair growth on scalp skin in healthy volunteers 
 
Planned trial period:  
January 2018 – June 2018 
 
Phase of development:  
Phase 2 
Objectives: 
 
Primary objective: 
The primary objective of this trial is to evaluate the efficacy of FOL-005 on scalp hair density in 
healthy male subjects when applied intradermally three times weekly for 12 weeks. 
Secondary objectives are: 
The secondary objective of this trial is to evaluate the efficacy of FOL-005 on scalp hair density 
in healthy male subjects when applied intradermally three times a week for 8 weeks and to 
evaluate the safety and tolerability of 12 weeks of treatment with FOL-005 in healthy male 
subjects. 
 
 
 


Sponsor: Follicum AB 
 
Clinical Trial Protocol 
Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
Final 
3 of 58 
07 November 2017 
 
Methodology: 
The trial is a multicentre, randomised, double-blind, placebo controlled phase 2 trial 
60 healthy bald male subjects diagnosed with androgenic alopecia (Norwood/Hamilton grade 
3V to 4/4a), who are between 18 and 55 years old and provide written informed consent will 
be eligible for inclusion. 
 
The trial period will consist of a screening period of up to 1 week followed by 12 weeks of 
dosing, three times per week. Each subject will receive two doses of the four trial treatment 
doses (0.00625, 0.025, 0.050, and 0.100 μg respectively) and the placebo dose. On each 
volunteer, two treatment areas will be selected on the head and the two selected doses will 
be allocated to the respective treatment areas according to the randomisation scheme. The 
treatment areas will be selected on the border between the bald surface and the surface 
with hair.  
 
The subjects will be screened for eligibility at the screening visit where a physical examination 
and assessment of vital signs will be performed. Blood samples for safety and laboratory 
assessment will be taken. The subjects will return to the clinic for the inclusion visit (visit 1, 
day 1) 3 to 21 days later. If the subject is eligible for inclusion, the 2 treatment areas will be 
shaved and the centre of each treatment area where the trial treatments will be applied will 
be marked with a tattooed dot. 
At visit 2, day 5, the first trial treatment application will be performed after TrichoScan 
imaging of the treatment areas. Subjects will then return to the clinic for treatment 
application three times per week with at least one day in between.  
 
All subjects who have received at least one dose of trial drug will go through the procedures 
for safety and efficacy assessments at last visit (EOT, visit 38). 
 
All adverse events will be followed until resolved or stabilised. Procedures for removal of 
subjects from therapy or assessments are described in Section 8.7. 
 
Number of subjects: 
A total of 60 healthy male subjects will be included.  
Each subject will be treated at two sites. Each site will be treated with different 
treatments. 
Thus, a total of 120 treatment areas will be available for treatment on the 60 subjects 
 
Inclusion criteria: 
The subjects must meet all of the following criteria to be eligible to enter the trial: 
1. Healthy male, aged 18-55 years 
2. Androgenetic alopecia (AGA)) – Norwood/Hamilton grade 3V to 4/4a [1]   
3. Caucasian, skin type I – IV according to Fitzpatrick’s classification [2] 
4. Willing to have treatment areas shaved for TrichoScan® measurement marked with 
small semi-permanent dot tattoos  
5. Willing and able to comply with scheduled visits 
6. Willing to maintain the same hygiene products and skin cleansing habits during the 
trial period. 
7. Willing to continue to use the currently used shampoo throughout the course of the trial. 


Sponsor: Follicum AB 
 
Clinical Trial Protocol 
Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
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8. Following verbal and written information about the trial, the subject has to provide 
signed and dated informed consent before any trial related activity is carried out. 
 
Exclusion criteria: 
Subjects meeting any of the following criteria will not be permitted to enter the trial: 
1. Damaged skin in or around test sites including sunburn, uneven skin tones, tattoos, 
scars or other disfiguration of the test sites risking interfering with investigational 
evaluations 
2. Any dermatological disorders of the scalp which might interfere with the application 
of IMP or examination method, such as fungal or bacterial infections, seborrheic 
dermatitis, psoriasis, eczema, folliculitis or scalp atrophy 
3. Any skin pathology (e.g. scar, nevus) or general condition (e.g. uncontrolled thyroid 
diseases) that in the investigator’s opinion can interfere with the evaluation of the 
treatment areas or requires topical or systemic therapy  
4. History of active hair loss due to alopecia areata, scarring alopecia, diffuse telogen 
effluvium or conditions other than androgenetic alopecia 
5. Use of or planned use of any shampoo with expected medicinal effect on the scalp 
(e.g. but not limited to antifungal or anti-dandruff shampoo, shampoo containing urea, 
caffeine or acetylsalicylic acid, etc.) during the course of the trial 
6. Known or suspected allergy or sensitisation to any of the IPs or excipients 
7. Immunological disorders such as alopecia areata, and systemic lupus erythematosus 
and other systemic known autoimmune disorders 
8. Diabetes mellitus 
9. Topical treatments for hair growth (minoxidil, anti-androgens or other agents known 
to affect hair growth) in the last 6 months 
10. Topical scalp over-the-counter (OTC) or cosmetic treatments including shampoos 
known to affect hair growth in the last 4 weeks 
11. Topical treatments of the scalp including corticosteroids, tacrolimus, retinoids in the 
last 2 months or other treatments that may affect hair growth  
12. Platelet rich plasma (PRP) treatment on scalp during the last 12 months 
13. Systemic therapy using retinoids, cyclosporine within the last 3 months 
14. Systemic treatment with beta blockers or corticosteroids, scalp procedures e.g. 
surgery, laser, light, micro-needling within the last 6 months 
15. Finasterid (e.g. Propecia®) or Dutasteride intake in the last 12 months, or any 
systemic hair therapy medication in the last 12 months 
16. Other systemic therapy which in the opinion of the investigator might affect hair 
growth 
17. Known needle fear or loss of consciousness while having blood sample taken or 
receiving injections 
18. History of any acute (e.g. acute infections) or chronic illness (e.g. psoriasis, atopic 
dermatitis, porphyria) or known skin cancer that in the opinion of the investigators 
might confound the results of the trial 
19. History or clinical signs of keloids or hypertrophic scars 


Sponsor: Follicum AB 
 
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Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
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20.  Positive HIV-Antibody, HBs-Antigen or HCV-Antibody-Test at screening 
21. Elevated values for vital signs:  
• 
blood pressure: systolic above 160 mmHg, diastolic above 95 mmHg 
• 
heart rate: above 100 beats/min. 
22. Current or within 2 weeks prior to first dosing use of vasodilating drugs (e.g. 
Pentoxifyllin, nitroglycerine) or anticoagulating drugs (e.g. heparine, cumarines, new 
oral anticoagulants, regular intake of acetylsalicylic acid) 
23. Current or within 3 months prior to first dosing use of anti-inflammatory medication 
(ibuprofen, paracetamol is permitted), corticosteroids (nose drops, eye drops and/or 
inhalers are permitted) or immunosuppressive drugs taken for more than 2 
consecutive weeks 
24. Current or within the last 6 months history of severe dietary or weight changes 
25. Hair transplantation at any time 
26. Known sensitization to cosmetic hair dyes or hypersensitivity to ingredients of the 
IMP or tattoo ink. 
27. Planned or scheduled subject surgery or hospitalisation during the course of the trial 
28. Any condition for which the investigator determines that the subject could be placed 
under undue risk. 
29. Participation in any clinical trial within the last four weeks 
30. Previously randomised in this trial 
31. Subject is institutionalized because of legal or regulatory order 
32. Close affiliation with the investigator (e.g. a close relative) or persons working at the 
trial site, or subject that is an employee of sponsor 
33. In the opinion of the investigator unlikely to comply with the clinical trial protocol 
 
Investigational products, dose and mode of administration: 
 
The trial treatments will consist of three times per week application of: 
• 
FOL-005 0.00625 μg solution, or 
• 
FOL-005 0.025 μg, or 
• 
FOL-005 0.050 μg, or 
• 
FOL-005 0.100 μg, or 
• 
FOL-005 placebo. 
The treatment will be randomized to the 120 treatment areas in the ratio of: 5:5:5:5:4, i.e. 5 
of each active treatment and 4 of placebo.  
 
The investigational products will be administered as a local intradermal injection of 50 μl 
solution into the skin. 
Treatment areas 
Two mini-zones (circle of 1.5 cm diameter), located on 2 contra-lateral zones, the right and 
left sides of the frontal areas of the scalp. Areas should be located in a transitional area of 
hair loss. The middle of each treatment area will be identified by a dot micro-tattoo, to 
ensure that the same area is treated, documented and evaluated throughout the study. 


Sponsor: Follicum AB 
 
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Protocol: FCS-002, version: 1.0 
 
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Duration of treatment: 
 
In total 12 weeks of dosing three times weekly 
 
Assessments  
Efficacy assessment: 
• 
Hair growth parameters on treatment areas using TrichoScan® software at 
Baseline and weeks 8 and 12. 
 
Safety 
assessments: 
• 
Adverse events 
• 
Local tolerability 
• 
Vital signs including supine systolic and diastolic blood pressure (mmHg), supine 
heart rate (beats per minute), body temperature  
• 
Physical examination including general appearance, mouth and throat, ears (left 
and right), lungs, abdomen, neurological  
• 
Blood and Urine sampling  
 
Criteria for evaluation: 
 
Efficacy variables: 
• 
Cumulative hair thickness (mm/cm²) 
• 
Hair thickness (μm/cm², mean median) 
• 
Hair length (mm/cm2; mean, median) 
• 
Total hair density (n/cm2) 
• 
Terminal hair density (n/cm2) 
• 
Vellus hair (<40μm thick) density (n/cm2) 
• 
Total hair growth (μm/day/cm2) 
• 
Hair growth (μm/day/cm2, mean median)  
• 
Anagen hair density (n/cm2) 
• 
Telogen hair density (n/cm2) 
 
Safety and tolerability variables: 
• 
Any adverse events reported (including change in vital signs, physical examination 
and safety laboratory parameters) 
• 
Any adverse drug reaction reported (including change in vital signs, physical 
examination and safety laboratory parameters) 
• 
The reasons for withdrawal from the study 
• 
Local tolerability; Erythema, Haematoma, dyspigmentation, induration and 
pain/discomfort will be assessed on a 4-graded scale (none, mild, moderate and 
severe) 
 


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Protocol: FCS-002, version: 1.0 
 
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Endpoints: 
 
Primary endpoint: 
Change from baseline of total hair density (No. of hairs per cm2) on the scalp after 
12 weeks of treatment 
 
Secondary endpoints are: 
Change from baseline of total hair density (No. of hairs per cm2) on the scalp after 8 weeks 
of treatment 
 
Change from baseline of hair growth parameters after 8 and after 12 weeks of treatment: 
• 
Cumulative hair thickness (mm/cm²) 
• 
Hair thickness (μm/cm², mean median) 
• 
Hair length (mm/cm2; mean, median) 
• 
Terminal hair density (n/cm2) 
• 
Vellus hair (<40μm thick) density (n/cm2) 
• 
Total hair growth (μm/day/cm2) 
• 
Hair growth (μm/day/cm2, mean median)  
• 
TrichoScan Anagen/Telogen ratio 
• 
Proportion of anagen hairs (%) 
• 
Proportion of telogen hairs (%) 
• 
Proportion of vellus hair (%) 
 
To evaluate the safety based on: 
• 
Any adverse events and adverse drug reactions reported 
• 
Local tolerability assessments 
• 
Vital signs and physical examination 
• 
Abnormal safety laboratory parameters 
 
Statistical methods: 
Summary tables (descriptive statistics and/or frequency tables) will be provided for 
screening and/or baseline variables, efficacy variables, and safety variables.  
Continuous variables will be presented by descriptive statistics (n, mean, median, standard 
deviation, minimum, and maximum). Frequency counts and percentage of subjects within 
each category will be provided for categorical data. Summaries will be provided for each 
treatment dose, if applicable.  
Descriptive summaries by study center will be presented for the primary efficacy endpoint.  
 
Hypothesis 
Since this is an exploratory trial no formal hypotheses are postulated. Comparisons by 
means of p-values will be interpreted in a descriptive manner. 
 
Efficacy analysis:  
Statistical analyses will be performed using two-sided tests and confidence intervals, as 
appropriate. The primary efficacy endpoint, the change from baseline for hair density on 
the scalp after 12 weeks, will be analysed using the exact Wilcoxon signed rank test to test 
versus zero. The secondary efficacy endpoints will be analysed using the same 
methodology as in the analysis of the primary efficacy endpoint.  
 
Safety analysis:  
All AEs reported during the trial period will be listed, documenting course, severity, 
investigator assessment of the relationship to the IP, and outcome. AEs will be coded using 
the MedDRA mapping system and tabulated by system organ class (SOC) and by 
preferred term. Listings of serious adverse events (SAE) and subjects who prematurely 
discontinued treatment due to AEs will be given. 
Safety laboratory parameter (hematology, clinical chemistry) and vital signs will be 


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Protocol: FCS-002, version: 1.0 
 
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summarized descriptively, including changes from baseline. Urinalysis outcomes and 
outcomes of local tolerability assessments will be summarized by frequency counts. 
 
Analysis populations:  
Safety summaries will be performed on the safety analysis set. The Per-protocol set will be 
considered the primary efficacy subset of subjects. The Full analysis set will be used for a 
sensitivity analysis of the primary efficacy variable only. 
 
 
 
 
 


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Trial flow chart 
 
 
a) The screening period is defined as the time between visit 0 and visit 1. The screening period 
will vary in length to accommodate flexibility in the planning of subject visit schedule. 
b) The physical examination will include: General appearance, mouth and throat, ears (left and 
right), lungs, abdomen, neurological 
c) Vital signs will include: Systolic and diastolic blood pressure (mmHg), heart rate (beats per 
minute), and body temperature 
d) The treatment areas will be evenly placed on the scalp 
e) The dot tattoo will be repeated if necessary during the course of the trial. Ensure that this 
performed at least 6 days prior to the next TrichoScan assessment.  
f) 
TrichoScan imaging will be performed without hair dye 
g) Haematology: haemoglobin, white blood cell count including differential cell count, red blood 
cell count, platelet count, coagulation (partial thromboplastin time and prothrombin time); 
Clinical Chemistry: Glucose, creatinine, total bilirubin, gamma-glutamyltransferase (GGT), 
alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), Electrolytes (Na, K), 
lactate dehydrogenase (LDH), C-reactive protein (CRP), total cholesterol 
h) Urine analysis (urine qualitatively): blood, ketones, glucose, protein, pH, nitrites, leucocytes, 
microscopy if results are positive for blood or protein 
i) 
End of Treatment (EoT) procedures should as far as possible be completed for all subject.  


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Protocol: FCS-002, version: 1.0 
 
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2 
THE TABLE OF CONTENTS 
Section 
Page 
 
Trial flow chart ............................................................................................... 9 
2 
THE TABLE OF CONTENTS ................................................................................. 10 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................. 13 
 
List of Abbreviations ................................................................................... 13 
 
Definition of Terms...................................................................................... 13 
4 
INVESTIGATORS AND TRIAL ADMINISTRATIVE STRUCTURE ........................ 14 
5 
INTRODUCTION .................................................................................................... 16 
 
Background ................................................................................................. 16 
 
Potential Risks and Benefits ...................................................................... 17 
6 
TRIAL OBJECTIVES ............................................................................................. 18 
 
Primary Objective ........................................................................................ 18 
 
Secondary Objective ................................................................................... 18 
7 
INVESTIGATIONAL PLAN .................................................................................... 19 
 
Trial Design and Plan-Description ............................................................. 19 
 
Trial Procedures .......................................................................................... 20 
7.2.1 
Schedule of Trial Events ............................................................. 20 
 
Discussion of Trial Design, Including the Choice of Control Groups ..... 21 
 
Trial Period .................................................................................................. 21 
 
End of Trial .................................................................................................. 21 
8 
SELECTION OF TRIAL POPULATION ................................................................. 22 
 
Subject recruitment..................................................................................... 22 
 
Number of Subjects .................................................................................... 22 
 
Inclusion Criteria ......................................................................................... 22 
 
Exclusion Criteria ........................................................................................ 22 
 
Subject Screening Log ............................................................................... 24 
 
Subject Randomisation .............................................................................. 24 
 
Removal of Subjects from Therapy or Assessment ................................. 24 
 
Premature Termination of the Trial ............................................................ 25 
9 
TREATMENT OF SUBJECTS ............................................................................... 26 
 
Investigational Products ............................................................................. 26 
9.1.1 
Treatment Regimens................................................................... 26 
9.1.2 
Identity of Investigational Products .............................................. 27 
9.1.3 
Packaging and Labelling of Investigational Products ................... 27 
9.1.4 
Storage and Handling of Investigational Products ....................... 27 
 
Method of Assigning Treatment areas ....................................................... 28 
 
Selection of Doses in the Trial ................................................................... 28 
 
Selection and Timing of Dose for Each Subject ....................................... 28 
 
Blinding........................................................................................................ 29 
 
Randomisation ............................................................................................ 29 
 
Breaking the Randomisation Code ............................................................ 30 
9.7.1 
Un-blinding of Individual Subject Treatment ................................ 30 
 
Prior and Concomitant Therapy ................................................................. 31 
9.8.1 
Disallowed Concomitant Therapy and Procedures ...................... 31 
 
Treatment Compliance ................................................................................ 31 
 Drug Accountability .................................................................................... 31 
10 
TRIAL ASSESSMENTS AND PROCEDURES ...................................................... 32 
 Endpoints .................................................................................................... 32 
 Efficacy Assessments ................................................................................ 32 
10.2.1 
Efficacy Variables ....................................................................... 32 
10.2.2 
Methods for Efficacy Assessments: TrichoScan imaging and 
measurement .............................................................................. 32 


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10.2.2.1 
Determination of Clinical Response to Investigational Product .... 32 
 Demographic and Other Baseline Characteristics.................................... 33 
10.3.1 
Demographic and Baseline Data ................................................. 33 
10.3.2 
Medical History ........................................................................... 33 
10.3.3 
Prior Medication .......................................................................... 33 
10.3.4 
Concomitant Medication .............................................................. 33 
 Safety Assessments ................................................................................... 34 
10.4.1 
Safety Variables .......................................................................... 34 
10.4.2 
Adverse Events ........................................................................... 34 
10.4.3 
Physical Examination .................................................................. 34 
10.4.4 
Vital Signs ................................................................................... 34 
10.4.5 
Laboratory Assessments ............................................................. 35 
10.4.6 
Local tolerability .......................................................................... 35 
 Procedures .................................................................................................. 36 
10.5.1 
Screening period (Day -21 to -1) ................................................. 36 
10.5.2 
Experimental phase .................................................................... 37 
 Criteria for discontinuation of subject due to local intolerance and 
further proceedings .................................................................................... 39 
11 
ADVERSE EVENTS ............................................................................................... 40 
 Definitions ................................................................................................... 40 
11.1.1 
Adverse Event............................................................................. 40 
11.1.2 
Adverse Reaction ........................................................................ 40 
11.1.3 
Unexpected Adverse Reaction .................................................... 40 
11.1.4 
Serious Adverse Event ................................................................ 40 
 Reporting of Adverse Events ..................................................................... 41 
 Reporting of Serious Adverse Events ....................................................... 42 
 Precautions/Overdose ................................................................................ 43 
 Pregnancy .................................................................................................... 43 
12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ................ 44 
 Statistical and Analytical Plans .................................................................. 44 
12.1.1 
Data Sets to be Analysed ............................................................ 44 
12.1.2 
Definitions ................................................................................... 44 
12.1.3 
Statistical Issues ......................................................................... 44 
12.1.4 
Summary Statistics ..................................................................... 45 
12.1.5 
Efficacy Analyses ........................................................................ 45 
12.1.6 
Demographic and Other Baseline Characteristics ....................... 45 
12.1.7 
Exposure to Treatment ................................................................ 45 
12.1.8 
Prior and Concomitant Treatment ............................................... 45 
12.1.9 
Adverse Events ........................................................................... 45 
12.1.10 
Medical History ........................................................................... 45 
12.1.11 
Other Safety Assessments .......................................................... 46 
 Determination of Sample Size .................................................................... 46 
 Justification for the sample size ................................................................ 46 
12.3.1 
Introduction ................................................................................. 46 
12.3.2 
Expected baseline hair density and expected standard deviation 47 
12.3.3 
Sample size Formula .................................................................. 47 
12.3.4 
Results ........................................................................................ 47 
 Procedures for Reporting any Deviation(s) from the Original Statistical 
Analysis Plan ............................................................................................... 48 
13 
INVESTIGATOR/SPONSOR RESPONSIBILITIES ................................................ 49 
 Ethics ........................................................................................................... 49 
13.1.1 
Independent Ethics Committee (IEC) .......................................... 49 
13.1.2 
Ethical Conduct of the Trial ......................................................... 49 
13.1.3 
Subject Information and Consent ................................................ 49 
 Regulatory Authority ................................................................................... 49 


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 Subject Data Protection .............................................................................. 49 
 Other Ethical and Regulatory Issues ......................................................... 50 
 Good Clinical Practice ................................................................................ 50 
13.5.1 
Legal Preconditions .................................................................... 50 
13.5.2 
Protocol conformity ..................................................................... 50 
 Subject Records and Source Data ............................................................. 51 
 Access to Source Data and Documentation.............................................. 51 
 Monitoring ................................................................................................... 51 
 Data Management ....................................................................................... 52 
 Quality Assurance and Audit ..................................................................... 52 
 Record Retention ........................................................................................ 52 
 Insurance ..................................................................................................... 53 
 Report and Publication ............................................................................... 53 
14 
REFERENCE LIST ................................................................................................ 54 
15 
SIGNATURE PAGES ............................................................................................. 55 
 
LIST OF APPENDICES 
Appendix 1 Schematic IP Dilution Manual for the FOL-005 IMP ........................................... 57 
 
LIST OF TABLES 
Table 1 
Trial flow chart .................................................................................................... 20 
Table 2 
Laboratory parameters ....................................................................................... 35 
Table 3 
Local skin tolerance/ side effects ........................................................................ 36 
Table 4 
Number of fully evaluable subjects needed in order to get 80 % probability to get 
a two-sided p-value less than 5 % by some values for the expected standard 
deviation and by some differences in hair counts from baseline until end of 
treatment. ........................................................................................................... 47 
 
LIST OF FIGURES 
Figure 1 
Trial Design 
 
 
 
 
 
 
 
 
19 
Figure 2 
Treatment areas 
 
 
 
 
 
 
 
26 
Figure 3 
Schematic picture of distance measurements 
 
 
 
25 
 
 


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3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
List of Abbreviations 
AE 
Adverse Event 
ALAT 
Alanine Aminotransferase 
ALP 
Alkaline Phosphatase 
ASAT 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
CA 
Competent Authority 
eCRF 
Electronic Case Report Form 
EEA 
European Economic Area 
EMA 
European Medicines Agency 
EoT 
End of Treatment 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation 
ID 
Identification Data 
IEC 
Independent Ethics Committee 
IP 
Investigational Product(s) 
MD 
multiple dose 
PPS 
Per-Protocol Set 
Q1 
First quartile 
Q3 
Third quartile 
SAD 
single ascending dose 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
VAS 
Visual Analogue Scale 
VASI 
Visual Analogue Scale for Itching 
 
 
Definition of Terms 
Competent Authority 
A government body or government appointed body that has legal 
authority to approve or disapprove clinical trials 


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4 
INVESTIGATORS AND TRIAL ADMINISTRATIVE STRUCTURE 
PRINCIPAL INVESTIGATOR 
Name: 
Prof. Dr. Ulrike Blume-Peytavi 
Address: 
Klinik für Dermatologie, Venerologie und Allergologie, Charité-Universitätsmedizin 
Berlin 
Charitéplatz 1 - 10117 Berlin 
Phone: 
+49 (0)30 450 518 122  
E-mail: 
crc-office@charite.de; ulrike.peytavi@charite.de 
 
SPONSOR’S TRIAL DIRECTOR 
Name: 
Jan Alenfall 
Address: 
Follicum AB 
 
Scheelevägen 22 
 
SE-223 63 Lund 
 
Sweden 
Phone: 
+46 (0)46 19 21 97 
 
+46 (0)709 31 51 15 
E-mail: 
jan.alenfall@follicum.com 
CONTRACT RESEARCH ORGANISATION 
Name: 
Dr. Anke Müller  
Address: 
bioskin GmbH 
 
Burchardstr. 17 
 
20095 Hamburg 
 
GermanyPhone: +43 40 60689755 
Fax: 
+43 40 60689730 
E-mail: 
anke.mueller@bioskincro.com 
LABORATORY FOR SAFETY PARAMETER ANALYSIS  
Name:    
LKF- Laboratorium für Klinische Forschung GmbH 
Address:  
Lise-Meitner-Straße 25-29  
 
24223 Schwentinental 
 
Germany 
Phone:  
+49 4307 8276 0  
Fax:  
+49 4307 8276 79 
E-mail:  
project@lkf-kiel.de   
  
TRICHOLOG ASSESSMENT 
Name:    
Prof. Dr. Rolf Hoffmann  
Address:  
TRICHOLOG GmbH 
 
In den Eschmatten 24  
 
79117 Freiburg i. Brsg. 
 
Germany 
Phone:  
+49 761 6800112  
Fax:  
+49 761 6800113 
E-mail:  
info@tricholog.de 
 
PROJECT LEADER 
Name: 
Johan Quensel 
Address: 
Follicum AB 
 
Scheelevägen 22 
 
SE-223 63 Lund 
 
Sweden 
Phone: 
+46 (0)760 46 67 44 


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E-mail: 
johan.quensel@follicum.com 
BIOSTATISTICIAN 
Name: 
Maciej Hoffman-Wecker  
Address: 
bioskin GmbH 
 
Burchardstr. 17 
 
20095 Hamburg 
 
Germany 
Phone: 
+43 40 60689737 
Fax: 
+43 40 60689730 
E-mail: 
maciej.hoffman-wecker@bioskincro.com 
 
PHARMCOVIGILANCE/ SAFETY MEDICAL MONITOR  
Name:  
Dr. Monika Storm 
Address: 
FGK Clinical Research GmbH 
 
Heimeranstr. 35 
 
80339 Munich 
 
 
GermanyPhone:  
+49 4340 702 9992 
E-mail:  
monika.storm@fgk-cro.de 
 
 
 
 
Serious Adverse Event Reporting 
 
 
E-mail:  
safety@fgk-cro.com 
FAX:   
+49 89 893 119 180 
 


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5 
INTRODUCTION 
 
Background 
Hair follicle morphogenesis and growth is controlled by a complex network of sequential 
activation and inactivation of autocrine, paracrine and endocrine signalling pathways [3]. The 
regulation and molecules involved are not yet fully known. There are three phases of the hair 
cycle: a growth phase (anagen), a regression phase (catagen), and a resting phase (telogen). 
The duration of the phases depends on the type and localization of the hair follicle. For instance 
body hair follicles remain for a shorter period in anagen leading to shorter hair shaft length as 
compared to scalp hair follicles [4].  
Follicum AB develops peptides derived from human osteopontin with a focus on local 
application for modulation of hair growth. Osteopontin is a 32 kDa extracellular matrix 
glycoprotein with diverse immunomodulatory functions and has been associated with 
inflammation and fibrosis. Its synthesis is stimulated by calcitriol (1,25-dihydroxy- vitamin D3).  
Follicum’s initial finding was that a modified form of the glycoprotein osteopontin (OPN) induces 
hair growth in young mice, where the follicles are in telogen phase, after subcutaneous 
administration. There are reports on OPN to be present in hair follicles in a hair cycle 
dependant manner [5]. The first candidate drug is a synthetic peptide named FOL-005. This 
candidate peptide is comprised of 15 amino acids with a free N and C- terminal; the molecular 
weight is 1672 Da and the molecular formula C74H114N18O26. Except for hair growth promoting 
activity, it is considered that Follicum’s drug candidate FOL-005 does not possess any of 
osteopontin’s mentioned effects, as major functional parts of OPN have been deleted in the 
FOL-005 peptide.  
A possible link to the mode of action of FOL-005 could come from integrins. The modification 
of OPN was done in the region where the integrin binding sequence in OPN is located. The 
importance of a modified RGD sequence (specific 3 amino acid sequence in osteopontin) in 
hair growth may reveal an affinity to other receptors or other mechanisms than previously 
known. However, in Follicum’s compounds the RDG site is disrupted and the cryptic integrin-
binding site may become more active leading to a stronger interaction to these receptors. This 
may be the explanation for the better activity shown by the peptides compared to the full-length  
Trial Rationale 
In non-clinical in vivo studies in C57Bl/6 mice, treatment with low doses of FOL-005 showed 
significant anagen hair growth induction and complete hair growth was observed in almost all 
treated animals. 
Distribution of immune labelled FOL-005 and its binding properties has been studied in mice 
and human tissues. Subcutaneously injected FOL-005 was indicated to diffuse rapidly from 
the site of injection, and into deeper skin levels [6]. FOL-005 binding was mainly present in the 
Outer Root Sheet (ORS), being relatively dominating close to the base of the follicles, both in 
mice and human tissues [6, 7]. The strongest binding was detected in the anagen phase of 
hair growth. The FOL-005 peptide C-terminal and central amino-acid regions appears to be 
most important for its binding [7]. 
FOL-005 has been studied in a Phase I study in healthy male volunteers. FOL-005 was 
administered as intradermal injections in specified skin areas on the forefront of the thighs. 
After a single ascending dose phase, safety and efficacy was studied during 12 weeks in a 
multiple dose phase. In the multiple dose phase, four different doses of FOL-005 and 
placebo were injected 2 or 3 times weekly for 12 weeks.  


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A statistically significant up-regulation of hair growth with bell-shaped dose-response, with 
maximum effect at 0.025µg of FOL-005, was observed after twice or 3 times weekly 
administration for 12 weeks. No serious adverse events or other safety issues were 
recorded; FOL-005 was well tolerated [8].  
 
Potential Risks and Benefits 
No direct benefit is expected for subjects participating in early clinical trials. 
Preclinical toxicity studies have not shown any clinically visible changes or histological 
changes after subcutaneous injections to indicate any tolerability issue.  
In the First in Man (FIM) clinical trial, FOL-005 was well tolerated. No Serious Adverse Events 
were reported during the trial and no subject withdrew from treatment or had the treatment 
interrupted due to AEs. No severe AEs were reported. Local tolerability events, mostly 
assessed as procedure related, contributed to a majority of the reported events. These were 
almost exclusively of mild severity; only 2 injection site haematomas of moderate severity were 
reported.  
There were no differences in local AE frequency between doses, ranging from 0.005 to 0.500 
µg of FOL-005 or, between FOL-005 and placebo treatment. Neither were there any 
increases in frequency of AEs or in AE severity during treatment. In contrast, the frequency 
of reported local tolerance AEs decreased over time [8]. 
Considering the safety results in the FIM study, the foreseeable risks to the subjects of any 
FOL-005 related reactions are very low. 
The duration of trial FCS-002, will be identical to the FIM trial and the maximum dose (single 
doses as well as accumulated dose) will be lower than in the FIM trial. The application areas 
differ however between the trials; in the FIM trial administrations were performed on the 
thighs and in trial FCS-002 administrations will be performed on the scalp.  
The foreseeable risks of the subjects related to the trial procedures include allergic or 
hypersensitivity reactions to the tattoo or the disinfectants, and mild pain and local 
discomforts (e.g. haematoma) related to the intradermal injection of the peptide and blood 
samplings.  
The dot tattoos on the skin, which are required for high-level standardization, may cause 
transient local bleeding. Rarely, inflammation, injury or irritation of nerves occurs. The dye 
applied may cause sensitization e.g. contact eczema which occurs within hours or days after 
the application. The most common manifestations are pruritus, predominant oedema unlike 
typical eczema lesions (erythema associated with vesicles). This reaction progresses to a dry 
skin with desquamations and often requires the administration of a topical treatment. If 
tattoos do not fade within 3 months after trial end, the subject will be offered a free laser 
removal of the dot tattoo. 
The intradermal injection of the peptide as well as blood sampling may cause a short pain 
and mostly immediate local discomforts during the puncture. Occasionally a bruise may 
appear when a small amount of blood gets into the surrounding tissues. This normally 
disappears within a few days. Possible other side effects like thrombosis, infection, damage 
of nerves or surrounding tissues are very rare and almost negligible since only trained staff is 
involved in the trial. 


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6 
TRIAL OBJECTIVES 
 
Primary Objective 
The primary objective of this trial is to evaluate the efficacy of FOL-005 on scalp hair density 
in healthy male subjects when applied intradermally three times a week for 12 weeks. 
 
 
Secondary Objective 
The secondary objective of this trial is to evaluate the efficacy of FOL-005 on scalp hair 
density in healthy male subjects when applied intradermally three times weekly for 8 weeks 
and to evaluate the safety and tolerability of 12 weeks of treatment with FOL-005 in healthy 
male subjects. 


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7 
INVESTIGATIONAL PLAN 
 
Trial Design and Plan-Description 
The trial is a multicentre, randomized, double-blind, placebo controlled phase 2 trial. 
The trial centres will screen a sufficient number of subjects (approximately n = 90) to include 
60 eligible male subjects. Subjects withdrawn for IMP-unrelated reasons will be replaced if 
treatment was performed for less than 4 weeks. 
60 healthy male subjects, who are 18 to 55 years old and provide written informed consent will 
be included 
The trial period will consist of a screening period of up to 3 weeks followed by 12 weeks of 
dosing. Each subject will receive their first doses at visit 2 (day 5). Subjects will then return to 
the clinic for treatment application 3 times per week with at least one day in between. 4 active 
dose strengths and one placebo dose will be used in the trial and each subject will be randomly 
assigned two of these 5 treatments. Thus, all 60 subjects will receive 2 doses.   
The subjects will be screened for eligibility at the screening visit where a physical examination 
and assessment of vital signs will be performed. Blood samples for HIV/Hep-b/Hep-c, safety 
and laboratory assessment will be taken. The subjects will return to the clinic for the inclusion 
visit (visit 1, day 1) 3 to 21 days later. If the subject is eligible for inclusion, the 2 treatment 
areas will be shaved and the centre of each treatment area where the trial treatments will be 
applied will be marked with a tattooed dot. 
At visit 2, day 3, the first TrichoScan imaging of dyed hair for determination of baseline total 
hair density per cm2 and the first trial treatment application will be performed on the treatment 
areas. Subjects will then return to the clinic for treatment application three times per week with 
at least one day in between.  
All subjects who have at least received one dose of trial drug will go through the procedures 
at the Follow up safety and efficacy assessments at the EoT visit. 
All adverse events will be followed until resolved or stabilised. Procedures for removal of 
subjects from therapy or assessments are described in Section 8.7. 
 
Trial Treatments 
50 μl of the trial treatments will be applied intradermally at each treatment site in the centre 
marked with a tattooed dot. The dilutions and preparation of vials will be performed at the 
centre, by blinded personnel. 
The trial treatments will consist of three times per week application of: 
• 
FOL-005 0.00625 μg solution, or 
• 
FOL-005 0.025 μg, or 
• 
FOL-005 0.050 μg, or 
• 
FOL-005 0.100 μg, or 
• 
FOL-005 placebo. 
Each subject will receive 2 trial treatments. The trial treatments will be randomised and a 
subject can receive any combination of the above 5 trial treatments except two of the same 
treatment.  The expected duration of participation in the trial will be maximum 87 days for each 
subject.  


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Figure 1 
Trial Design  
 
 
Trial Procedures  
 
7.2.1 Schedule of Trial Events 
The trial assessments described in the sections below are presented in detail in Section 10.2 
(efficacy assessments), Section 10.3 (demographic data and baseline characteristics) and 
Section 10.4 (safety assessments). Recording and reporting of AEs are described in detail in 
Section 11.  
The timing of all trial events is shown in Tables 1 - Trial Flow Chart 
 
Table 1 
Trial flow chart  
 
 
a) The screening period is defined as the time between visit 0 and visit 1. The screening period 
will vary in length to accommodate flexibility in the planning of subject visit schedule. 
b) The physical examination will include: General appearance, mouth and throat, ears (left and 
right), lungs, abdomen, neurological 
c) Vital signs will include: Systolic and diastolic blood pressure (mmHg), heart rate (beats per 
minute), and body temperature 
d) The treatment areas will be evenly placed on the scalp 


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e) The dot tattoo will be repeated if necessary during the course of the trial. Ensure that this 
performed at least 6 days prior to the next TrichoScan assessment.  
f) 
TrichoScan imaging will be performed without hair dye 
g) Haematology: haemoglobin, white blood cell count including differential cell count, red blood 
cell count, platelet count, coagulation (partial thromboplastin time and prothrombin time); 
Clinical Chemistry: Glucose, creatinine, total bilirubin, gamma-glutamyltransferase (GGT), 
alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), Electrolytes (Na, K), 
lactate dehydrogenase (LDH), C-reactive protein (CRP), total cholesterol 
h) Urine analysis (urine qualitatively): blood, ketones, glucose, protein, pH, nitrites, leucocytes, 
microscopy if results are positive for blood or protein 
i) 
End of Treatment (EoT) procedures should as far as possible be completed for all subject.  
 
 
Discussion of Trial Design, Including the Choice of Control Groups 
A randomised controlled blinded design is used. Such a design is most suitable to prevent 
and/or to minimize selection, performance, attrition, and detection bias. 
The primary objective of this trial is to evaluate the effect of FOL-005 on scalp hair growth in 
healthy male subjects.  
The TrichoScan is a reliable, well-validated phototrichogram method assessing the biological 
parameters of hair growth by combining dermoscopy with automatic digital image analysis for 
the measurement of human hair in situ. The TrichoScan system is designed to take 
reproducible images from shaved areas on the scalp. A good correlation between 
TrichoScan and manual evaluation of hair counts has been demonstrated [9, 10]. 
Safety and tolerability will be evaluated as secondary objectives. FOL-005 was considered 
safe and well tolerated in a previous phase 1 trial, FCS-001, as described in the 
investigator’s brochure.  
Each subject will have 2 treatment areas, A and B, evenly located on the scalp, at least 5 cm 
apart from each other. Treatment areas will be treated with either one of the following 
treatments: 0.00625 µg, 0.025 μg, 0.050 μg, 0.100 μg and placebo according to the 
randomisation schedule. 
 
Trial Period 
The trial is planned to start in January 2018 and be completed in June 2018. 
 
End of Trial 
The end of trial is defined as the date of the last subject’s last visit.  


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8 
SELECTION OF TRIAL POPULATION 
 
Subject recruitment 
Subjects will be recruited from subject databases and advertisements. 
 
Number of Subjects 
The trial is planned to include in total 60 male subjects. Subjects withdrawn for IMP-unrelated 
reasons will be replaced if treatment was performed for less than 4 weeks. 
 
Inclusion Criteria 
The subjects have to meet all of the following criteria to be eligible to enter the trial: 
1. 
Healthy male, aged 18-55 years 
2. 
Androgenetic alopecia (AGA)) – Norwood/Hamilton grade 3V to 4/4a [1] 
3. 
Caucasian, skin type I – IV according to Fitzpatrick’s classification [2] 
4. 
Willing to have treatment areas shaved for TrichoScan® measurement marked with 
small semi-permanent dot tattoos  
5. 
Willing and able to comply with scheduled visits 
6. 
Willing to maintain the same hygiene products and skin cleansing habits during the trial 
period. 
7. 
Willing to continue to use the currently used shampoo throughout the course of the trial. 
8. 
Following verbal and written information about the trial, the subject has to provide 
signed and dated informed consent before any trial related activity is carried out. 
 
Exclusion Criteria 
Subjects meeting any of the following criteria will not be permitted to enter the trial: 
1. 
Damaged skin in or around test sites including sunburn, uneven skin tones, tattoos, 
scars or other disfiguration of the test sites risking interfering with investigational 
evaluations 
2. 
Any dermatological disorders of the scalp which might interfere with the application of 
IMP or examination method, such as fungal or bacterial infections, seborrheic 
dermatitis, psoriasis, eczema, folliculitis or scalp atrophy 
3. 
Any skin pathology (e.g. scar, nevus) or general condition (e.g. uncontrolled thyroid 
diseases) that in the investigator’s opinion can interfere with the evaluation of the 
treatment areas or requires topical or systemic therapy  
4. 
History of active hair loss due to alopecia areata, scarring alopecia, diffuse telogen 
effluvium or conditions other than androgenetic alopecia 
5. 
Use of or planned use of any shampoo with expected medicinal effect on the scalp 
(e.g. but not limited to antifungal or anti-dandruff shampoo, shampoo containing urea, 
caffeine or acetylsalicylic acid, etc.) during the course of the trial 
6. 
Known or suspected allergy or sensitisation to any of the IPs or excipients 


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7. 
Immunological disorders such as alopecia areata, and systemic lupus erythematosus 
and other systemic known autoimmune disorders 
8. 
Diabetes mellitus 
9. 
Topical treatments for hair growth (minoxidil, anti-androgens or other agents known to 
affect hair growth in the last 6 months 
10. 
Topical scalp over-the-counter (OTC) or cosmetic treatments including shampoos 
known to affect hair growth in the last 4 weeks 
11. 
Topical treatments of the scalp including corticosteroids, tacrolimus, retinoids in the last 
2 months or other treatments that may affect hair growth  
12. 
Platelet rich plasma (PRP) treatment on scalp during the last 12 months 
13. 
Systemic therapy using retinoids, cyclosporine within the last 3 months 
14. 
Systemic treatment with beta blockers or corticosteroids, scalp procedures e.g. 
surgery, laser, light, micro-needling within the last 6 months 
15. 
Finasterid (e.g. Propecia®) or Dutasteride intake in the last 12 months, or any systemic 
hair therapy medication in the last 12 months 
16. 
Other systemic therapy which in the opinion of the investigator might affect hair growth 
17. 
Known needle fear or loss of consciousness while having blood sample taken or 
receiving injections 
18. 
History of any acute (e.g. acute infections) or chronic illness (e.g. psoriasis, atopic 
dermatitis, porphyria) or known skin cancer that in the opinion of the investigators might 
confound the results of the trial 
19. 
History or clinical signs of keloids or hypertrophic scars 
20. 
 Positive HIV-Antibody, HBs-Antigen or HCV-Antibody-Test at screening 
21. 
Elevated values for vital signs:  
• 
blood pressure: systolic above 160 mmHg, diastolic above 95 mmHg 
• 
heart rate: above 100 beats/min. 
22. 
Current or within 2 weeks prior to first dosing use of vasodilating drugs (e.g. 
Pentoxifyllin, nitroglycerine) or anticoagulating drugs (e.g. heparine, cumarines, new 
oral anticoagulants, regular intake of acetylsalicylic acid) 
23. 
Current or within 3 months prior to first dosing use of anti-inflammatory medication 
(ibuprofen, paracetamol is permitted), corticosteroids (nose drops, eye drops and/or 
inhalers are permitted) or immunosuppressive drugs taken for more than 2 consecutive 
weeks 
24. 
Current or within the last 6 months history of severe dietary or weight changes 
25. 
Hair transplantation at any time 
26. 
Known sensitization to cosmetic hair dyes or hypersensitivity to ingredients of the IMP 
or tattoo ink. 
27. 
Planned or scheduled subject surgery or hospitalisation during the course of the trial 
28. 
Any condition for which the investigator determines that the subject could be placed 
under undue risk. 
29. 
Participation in any clinical trial within the last four weeks 


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30. 
Previously randomised in this trial 
31. 
Subject is institutionalized because of legal or regulatory order 
32. 
Close affiliation with the investigator (e.g. a close relative) or persons working at the 
trial site, or subject that is an employee of sponsor 
33. 
In the opinion of the investigator unlikely to comply with the clinical trial protocol 
 
Subject Screening Log 
A screening log will be kept at the trial centres for all subjects seen during the enrolment period. 
Each screened subject will be allocated a unique screening number. In the subjects screening 
log, the screening number, the date of screening, age, and reason for non-inclusion should be 
stated. 
 
Subject Randomisation  
Subjects will be given a unique randomisation number at the first treatment visit (Visit 1). The 
randomisation number is a unique subject identifier used throughout the trial, in lieu of the 
subject’s name. 
 
Removal of Subjects from Therapy or Assessment 
Subjects are free to discontinue their participation in the trial at any time. Withdrawal from the 
trial will not affect or prejudice the subject’s further care or treatment. Subjects may be 
withdrawn from trial treatment and assessments at any time, if deemed necessary by the 
Investigator. 
Mandatory discontinuation criteria: 
• 
Withdrawn consent 
• 
Adverse events, which bring the subject at risk or might confound the result of the 
trial; 
• 
Occurrence of local intolerance according to specification in section 10.5 
• 
4 consecutive treatments and/or in total 7 missed treatments  
• 
Un-blinding 
• 
Trial terminated by Sponsor 
 
 Additional reasons that may result in withdrawal of subjects from this trial are:  
• 
Physicians' decision; 
• 
Start of medication in the subject which is susceptible to interfere with hair growth or 
with further study performance (e.g. 5a reductase inhibitor, anti-coagulative therapy, 
systemic immune suppression); 
• 
Any appearance of exclusion criteria during the trial; 
• 
Protocol deviations/violation; 
The reason and date the subject is withdrawn from the trial will be documented in the eCRF. 


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If a subject is withdrawn from further treatment with the IP, the investigator should attempt to 
complete the EoT visit. All adverse events should be followed up according to Section 11.2. 
If a subject is withdrawn from the trial, all data collected until the time of withdrawal will be used 
in the analyses. 
 
Premature Termination of the Trial 
The Investigator or the Sponsor may terminate this trial prematurely for any reasonable cause. 
In this case the Ethics Committee (EC) and Competent Authority (CA) should be informed 
promptly. 
Conditions that may warrant termination include, but are not limited to: 
• 
The discovery of an unexpected, significant, or unacceptable risk to the subjects 
enrolled in the trial, or potential trial subjects  
• 
A decision on the part of the Sponsor to suspend or discontinue development of the IP. 
If the CA obtains information that raises doubts about the safety or scientific validity of the 
clinical trial, the CA can suspend or prohibit the trial. Before the CA reaches its decision, it 
shall, except where there is imminent risk, ask the Sponsor and/or the investigator for their 
opinion, to be delivered within one week (Directive 2001/20/EC, Article 12, Section 1). 
If the trial is prematurely terminated or suspended for any reason, the investigator/institution 
should promptly inform the trial subjects and should assure appropriate therapy and follow-up 
for the subjects. 


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9 
TREATMENT OF SUBJECTS 
 
Investigational Products 
9.1.1 Treatment Regimens 
FOL-005 solution and placebo of FOL-005 solution will be administered at the trial centre. The 
solutions are intended for local intradermal injection into the skin. With each injection a volume 
of 50µl will be administered. The treatment areas will have a dot tattoo in the centre, edges will 
be drawn as dots with a skin marker, maximum once per week (Figure 2). 
Each subject will have 2 treatment areas, A and B, evenly located on the scalp, at least 5 cm 
apart from each other. Treatment areas will be treated with either of the following treatments: 
0.00625 µg, 0.025 μg, 0.050 μg, 0.100 μg and placebo according to the randomisation 
schedule. 
Figure 2 
Treatment areas 
 
 
Treatment areas will be on the balding scalp. Treatment sites have to be free of scars, 
tattoos or dermatological defects that might impair measurements. Treatment areas (1.5 cm 
diameter) are located on the scalp in the hair recession area of the frontotemporal and vertex 
regions and will be marked with a red dot tattoo in the middle, as depicted. Edges will be 
marked as dots using a skin temporary marker. 
To help relocate the tattoo dot the following distances should be documented: 
 
• 
R:  
Distance between the tattoo and the middle of the right tragus 
• 
L:  
Distance between the tattoo and the middle of the left tragus 
• 
N:  
Distance between the tattoo and the tip of the nose. 
 
 
 


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Figure 3 
Schematic picture of distance measurements 
 
 
 
 The minimal distance between treatment areas should be 5 cm. 
 
  
Instructions for Application 
Before clinical examination of the subject’s treatment areas and subsequent application of 
FOL-005, the treatment areas will be cleansed by the investigator or trial personnel using a 
standard skin disinfectant.  
The application of IP should be performed according to the following instructions: 
1. 
Inject 50 μl to the treatment area according to the subject’s specific randomisation list. 
Care should be taken to avoid injections at the very same spot on every visit. 
2. 
Discard injection device. 
3. 
Document injection. 
This procedure is repeated for each treatment area.  
9.1.2 Identity of Investigational Products 
The active ingredient, FOL-005, is a chemically synthesised 15 amino acid peptide, which is 
based on an endogenous part of osteopontin. The sequence is H-Val-Asp-Thr-Tyr-Asp-Gly-
Asp-Ile-Ser-Val-Val-Tyr-Gly- Leu-Arg. Each vial of the IP FOL-005, solution for injection 
contains 9 mL, 10 µg/mL of FOL-005. It further contains sodium chloride, sodium hydrogen 
phosphate, hydrogen chloride, sodium hydroxide and purified water. The placebo product 
contains diluent only and is identical in appearance to the active product. 
9.1.3 Packaging and Labelling of Investigational Products 
FOL-005, 10 µg/mL solution for injection, is manufactured and released for the trial by 
Recipharm Pharmaceutical Development AB, Solna, Sweden.  
All manufacturing is performed in accordance with current Good Manufacturing Practice 
(cGMP). 
The labelling of FOL-005, solution for injection, the diluent and the dilution vials will be 
according to §5, GCP-V.  
9.1.4 Storage and Handling of Investigational Products 
The FOL-005 solution for injection must be stored in a freezer at a temperature of <-20°C. 
The temperature of the freezer will be logged. 


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The IP will be stored at the trial site as required by local regulations and laws for the 
participating site.  
The IP, FOL-005, solution for injection will be thawed and reconstituted by dilution with isotonic 
phosphate buffer pH 7.4 into the following concentrations: 0.125, 0.5, 1.0, and 2.0 µg/mL, as 
described in the study specific IP dilution manual. A schematic overview of the IMP dilution 
manual is found in Appendix 1. The handling of placebo is also described in the study specific 
dilution manual. Lab personnel not otherwise involved in assessment procedures will handle 
the preparation of vials.  
 
Method of Assigning Treatment areas 
Two of the 5 investigational treatments will be randomly assigned to the 2 treatment areas 1 
and 2 according to the randomisation list for each subject. The treatment areas 1 and 2 will 
receive the same treatment throughout the trial period. 
 
Selection of Doses in the Trial 
The rationale for the choice of dose in the present trial is based on previous results from the 
phase I/IIa trial FCS-001  
In FCS-001 the subjects were dosed twice or three times per week at four individual areas of 
the thighs with injections of 50 µL resulting in 0.005 to 0.250 µg of FOL-005. The maximum 
efficacy measured both as increase in hair density as well as in percentage of responders, 
was found at 0.025 µg and the effect was more prominent after three administration times 
per week as compared to two times per week. FOL-005 was well tolerated at all tested doses 
and local tolerability AEs due to the injection procedure contributed to the majority of the 
reported events. Moreover, there was no detectable systemic absorption of FOL-005 at 
either of the doses.  
In the present study 50 µL of FOL-005 will be injected into two separate areas on the scalp. 
The scalp has a higher density of hair follicles than the thighs and the hair cycle intervals 
generally have a longer duration on the head, Therefore, it cannot be ruled out that the hair 
follicle on the scalp responds different to FOL-005 than hair follicles on the thighs The doses 
strengths in the present trial have therefore been selected to cover a range below and over 
the optimal dose strength identified in FCS-001, i.e. 0.025 µg. The selected doses are 
0.00625, 0.025, 0.050 and 0.10 µg and each subject will receive different doses at the two 
separate areas, or one dose and placebo. The total maximal dose given to one individual 
subject in this trial - 0.150 µg for the subjects receiving the 0.050 and 0.100 µg doses - is well 
below the maximum dose given in the previous trial where each subject received four active 
doses, a total of 0.405 µg at each occasion.  
Based on clinical safety data from the previous study and the selection of doses in the 
present study, it is assumed that this design provides a minimized potential risk and a high 
probability to estimate possible effects of FOL-005. 
 
Selection and Timing of Dose for Each Subject 
The dose regime in the study, 3 times per week, is selected based on the results in the 
phase I/IIa trial FCS-001 where the subjects were treated 2 or 3 times per week. The efficacy 
measured both as increase in hair density as well as in percentage of responders, was more 
prominent after administration three times per week as compared to two times per week. 
FOL-005 was well tolerated at all tested doses and there was no detectable systemic 
absorption of FOL-005 at either of the dosing regimens. Injection related AEs such as 
haematomas and erythema, were more frequent in the group treated 3 times per week as 


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compared to the group treated 2 times. This is considered to be a result of the injection 
procedure and not the active ingredient. No increase in systemic AEs was found with the 
more frequent dosing.  
 
Detailed descriptions of the treatment regimen and instructions for application of the IP are 
given in Section 9.1.1. 
Restrictions to follow during the treatment period are described in Section 9.8.1.  
 
Blinding  
This trial will be double-blinded, meaning that neither the subject nor the Investigator will know 
which treatment areas will receive which treatment (actives or placebo). The appearance of 
the IP does not differ between the placebo and the active treatments. 
The treatment of the subject’s treatment areas will be randomised as described in Section 9.2 
and the subjects will receive a subject and random number. . 
In order to ensure the double blindness in the trial, dilution of the IP will be done according to 
the Study Specific Laboratory Manual (see Appendix 1), by persons not otherwise involved in 
the trial. 
 
Randomisation  
Each randomised subject will be treated with 2 of the 5 trial treatments on the two treatment 
areas on the scalp. The two treatment areas (1 and 2) will be symmetrical placed on the scalp 
(see figure 2)  
Thus, the subject will be randomised to receive any of the following 10 treatment combinations: 
A: 
• 
FOL-005 placebo: 
• 
FOL-005 0.00625 μg: 
B 
• 
FOL-005 placebo: 
• 
FOL-005 0.025 μg: 
C 
• 
FOL-005 placebo: 
• 
FOL-005 0.050 μg: 
D 
• 
FOL-005 placebo: 
• 
FOL-005 0.100 μg: 
E 
• 
FOL-005 0.00625 μg: 
• 
FOL-005 0.025 μg: 
F 
• 
FOL-005 0.00625 μg: 
• 
FOL-005 0.050 μg: 
G 
• 
FOL-005 0.00625 μg: 
• 
FOL-005 0.100 μg: 
H 
• 
FOL-005 0.025 μg 
• 
FOL-005 0.050 μg: 


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I 
• 
FOL-005 0.025 μg 
• 
FOL-005 0.100 μg: 
J 
• 
FOL-005 0.050 μg: 
• 
FOL-005 0.025 μg 
 
Each of these 10 combinations may be allocated in two ways: First treatment on area 1 and 
second treatment on area 2 or vice visa. 
The total allocation ratio of treatments will be 5:5:5:5:4 where 4 depicts placebo. 
In general, computer generated randomisation lists will be created containing one 
randomisation scheme per subject.  
Upon signature of informed consent (screening period) each subject receives a 5-digit patient 
identification number, which is composed of: 
Digits 1 and 2: 
trial center (01, 02, 03, etc.)  
Digits 3, 4 and 5: 
individual screening number within the center (consecutively in the 
order of screening within the center: 001, 002, etc.)  
Subjects who are eligible for enrollment into the trial will obtain a random number (501, 502, 
503, etc.) The random number will not be reused if a subject discontinues the trial. 
Subjects discontinued from the trial for IMP-unrelated reasons with treatment for less than 4 
weeks will be replaced (see section 7.1). The replacement subject will receive the same 
treatments as the discontinued subject. The original randomization number will be replaced by 
a new randomization number generated by the last two digits of the original number preceded 
by 6 (e.g. original random number is 553; replacement random number is 653).  
In order to further avoid bias of the results, the trial biostatistician will also be blinded and the 
preparation of the randomisation lists and envelopes are therefore performed by psy consult 
scientific services, Frankfurt, Germany, not directly involved in the study.  
 
Breaking the Randomisation Code 
9.7.1 Un-blinding of Individual Subject Treatment 
The trial sites will receive sealed envelopes containing a list of individual treatment codes. The 
envelopes will be kept by unblinded staff members at the trial site.  
The unblinded staff will keep the envelopes in a secure, limited access location to prevent 
inadvertent breaking of the blind of the investigator. The double blindness must be maintained 
throughout the trial.  
Suspected unexpected serious adverse reactions (SUSARs) will be unblinded for reporting to 
regulatory agencies and ethics committees. The pharmacovigilance team at FGK Clinical 
Research GmbH, Munich, Germany will be supplied with sealed envelopes of the 
randomization list to break the trial blind as required for regulatory reporting purposes. 
However, the investigator, sponsor, and blinded trial team will be kept blinded to treatment 
allocation. The information with regards to unblinding will be stored in a secure environment 
accessible only to pharmacovigilance team. 
If the code has been broken for a subject, the subject will be withdrawn from the trial and 
procedures accompanying withdrawal are to be performed.  


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Prior and Concomitant Therapy 
The use of prior medication used up to 4 weeks before study start and all concomitant 
medication (including Over the Counter and herbal medicines) by the subject will be recorded 
in the appropriate section of the eCRF up to the End of Trial Visit. 
Medication, which is considered necessary for the subject’s safety and well-being, may be 
given at the discretion of the Investigator. However, concomitant medication administered 
during the trial may lead to withdrawal of the subject from the trial (see Section 8.7) or 
subsequent exclusion form the PP analysis population if considered to be compromising the 
trial outcome. 
9.8.1 Disallowed Concomitant Therapy and Procedures 
The following treatments and/or procedures are prohibited during the trial: 
• 
Prolonged UV exposition and UV tanning beds; subjects are advised to wear 
hats/caps while outside 
• 
Sauna will not be permitted during the trial 
• 
Use of any topical drug on the treatment area(s) except for subject’s usual shampoo 
and hair care/cosmetic products as long as they do not claim to increase hair growth 
• 
Use of any washes using alcohol, vinegar or other astringents, including peeling 
agents on the treatment areas 
• 
Hair removal on skin treatment areas, e.g. waxing and shaving 
 
The following should be avoided during the trial: 
• 
More than once per day bathing/swimming 
• 
Normal washing/showering of the head / scalp is allowed but a 2 hour free interval 
before or after injection should be respected 
 
Treatment Compliance 
Application of IP in the treatment areas will be performed only at the trial centre by qualified 
medical staff of the trial team. Compliance of the subject regarding concomitant therapies and 
the use of cosmetics in the treatment areas will be documented throughout the trial. 
 Drug Accountability 
All IP supplied for this trial must be stored in a secure place. The Investigator or designated 
personnel at the trial site will keep a record of the inventory and dispensing of all IP. The 
Investigator is responsible for the drug accountability. 
The monitor will perform a final drug accountability at the site before the used IP can be 
destroyed or shipped back to Sponsor (unused IP). 
Study drug accountability, i.e., documentation of delivery, inventory, and return of IP will be 
maintained. Forms for documentation of the dilution procedures will be provided with the study 
specific IMP dilution manual.  


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10 TRIAL ASSESSMENTS AND PROCEDURES 
 Endpoints 
Primary endpoint: 
Change from baseline of total hair density (No. of hairs per cm2) on the scalp after 12 
weeks of treatment 
 
Secondary endpoints are: 
Change from baseline of total hair density (No. of hairs per cm2) on the scalp after 8 weeks 
of treatment 
 
Change from baseline of hair growth parameters after 8 and 12 weeks of treatment: 
• 
Cumulative hair thickness (mm/cm²) 
• 
Hair thickness (μm/cm², mean median) 
• 
Hair length (mm/cm2; mean, median) 
• 
Terminal hair density (n/cm2) 
• 
Vellus hair (<40μm thick) density (n/cm2) 
• 
Total hair growth (μm/day/cm2) 
• 
Hair growth (μm/day/cm2, mean median)  
• 
TrichoScan Anagen/Telogen ratio 
• 
Proportion of anagen hairs (%) 
• 
Proportion of telogen hairs (%) 
• 
Proportion of vellus hair (%) 
 
To evaluate the safety based on: 
• 
Any adverse events and adverse drug reactions reported 
• 
Local tolerability assessments 
• 
Vital signs and physical examination 
• 
Abnormal safety laboratory parameters 
 Efficacy Assessments 
10.2.1 Efficacy Variables  
• 
Cumulative hair thickness (mm/cm²) 
• 
Hair thickness (μm/cm², mean median) 
• 
Hair length (mm/cm2; mean, median) 
• 
Total hair density (n/cm2) 
• 
Terminal hair density (n/cm2) 
• 
Vellus hair (<40μm thick) density (n/cm2) 
• 
Total hair growth (μm/day/cm2) 
• 
Hair growth (μm/day/cm2, mean median)  
• 
Anagen hair density (n/cm2) 
• 
Telogen hair density (n/cm2) 
10.2.2 Methods for Efficacy Assessments: TrichoScan imaging and measurement 
10.2.2.1 Determination of Clinical Response to Investigational Product 
Photos of the treatment areas will be taken, and assessment of hair growth (hair count and 
hair density) calculated based on TrichoScan images. The analysis of the images will be 
performed centrally by a unit independent of the investigators. The analysis of the images will 
be performed while keeping the blind with regard to the treatment assignment. Assessment 
of hair growth will be performed as follows: 


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At Screening: 
1. Treatment areas will be trimmed over a large area to achieve a hair length of 1mm; 
2. Treatment areas (1.5 cm in diameter) will be selected and marked by a dot tattoo; 
At visit 1 (day 1): 
1. Selected treatment areas (1.5 cm in diameter) will be identified; 
2. Selected treatment areas will be trimmed over a large area to achieve a hair length of 
1mm; 
3. A TrichoScan image is taken without hair dye with the TrichoScan camera/optics 
system held always in the same position; 
At visit 2 (day 3): 
1. Selected treatment areas (1.5 cm in diameter) will be identified; 
2. A TrichoScan image is taken after hair dye with the TrichoScan camera/optics system 
held always in the same position prior to IMP treatment; 
The procedures of visit 1 are repeated for visits 23 and 35. The procedures for visit 2 are 
repeated for visits 24 and 36.  
For details of the TrichoScan imaging please refer to the TrichoScan manual. 
 Demographic and Other Baseline Characteristics 
10.3.1 Demographic and Baseline Data 
Demographic and baseline data will be collected at Visit 1. The following data will be collected: 
• 
Date of birth 
• 
Weight and height 
10.3.2 Medical History 
For the documentation of the medical history, relevant previous and concomitant diseases, 
allergies and familiar predispositions during the last year before the screening will be 
documented in the source data and the eCRF. 
The medical history will be obtained by asking the subject and by inspecting his/her medical 
records. Relevant medical and surgical history will be recorded at visit 1. 
10.3.3 Prior Medication 
Any medication taken by a subject within 12 month before the clinical trial is considered as 
prior medication. 
Use of prior medication will be recorded in the source data and the eCRF at Visit 1. 
10.3.4 Concomitant Medication 
Any medication taken by a subject during the clinical trial apart from the trial medication is 
considered as concomitant medication. 
Use of concomitant medication will be recorded in the source data and the eCRF at Visit 1 
and during the whole trial period if changed. 


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 Safety Assessments 
10.4.1 Safety Variables 
The following safety variables will be measured: 
• 
Adverse Events (nature and incidence) (see Section 11.2) 
• 
Physical examination 
• 
Vital signs (blood pressure [11], heart rate and body temperature) in sitting position 
• 
Laboratory safety assessments (haematology, clinical chemistry and urinalysis) 
• 
Local tolerability, as defined in section 10.4.6 
All local tolerability assessments must be performed by an investigator with dermatological 
expertise. As far as possible the same investigator shall assess a subject at all assessment. 
Safety of the IP after the first application of the single dose will be assessed by AE 
documentation approximately 15 minutes after injection, as well as throughout the whole trial. 
The assessing investigator will be identified in the source data at each visit. 
10.4.2 Adverse Events 
AEs will be recorded at Visit 1 and until the End of Trial.  
For further information of definitions and reporting of AEs and SAEs, see Section 10.5. 
10.4.3 Physical Examination 
Standard physical examinations will be performed at Screening, Visits 0, 36 and EoT visit. 
The physical examination will include: 
• 
General appearance 
• 
mouth and throat 
• 
ears (left and right) 
• 
heart 
• 
lungs 
• 
abdomen 
• 
neurological (rough inspection of strength and touch sensation)  
• 
axillary and inguinal lymph node palpation 
The parameters will be assessed as “normal” or “abnormal”. Abnormal findings will be specified 
and assessed as “clinically significant” or “not clinically significant”. 
Clinically significant abnormal findings at Visit 0 will be recorded in the source data and on the 
medical and surgical history page in the eCRF. New or worsening clinically significant 
abnormal findings at all subsequent visits will be recorded in the source data and on the AE 
page in the eCRF. 
10.4.4 Vital Signs 
Vital signs will be recorded at screening, visit 1, visit 36 and EoT visit.  
The following vital signs will be monitored as safety variables in a comfortable seated individual 
after 5 minutes: 
• 
Supine systolic and diastolic blood pressure (mmHg)  
• 
Supine heart rate (beats per minute) 


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• 
Body temperature measured in degrees Celsius (°C) according to site specific methods 
The observed values will be recorded and assessed as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
Clinically significant abnormal findings at Visit 1 will be recorded in the source data and on the 
medical and surgical history page in the eCRF. New or worsening clinically significant 
abnormal findings at all subsequent visits will be recorded in the source data and on the AE 
page in the eCRF. 
10.4.5 Laboratory Assessments 
A safety screen including standard safety laboratory parameters will be performed. Blood and 
urine samples for clinical chemistry and haematology evaluations will be collected at 
screening, 36 and at EoT visit. Serology samples will be taken at the screening visit and the 
result should be available at visit 1 before inclusion and randomisation. The samples will be 
analysed at the central laboratory LKF - Laboratorium für Klinische Forschung GmbH, 
Schwentinental, Germany. 
The observed values will be recorded and assessed as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
Clinically significant abnormal findings at Visit 1 will be recorded in the source data and on the 
medical and surgical history page in the eCRF. New or worsening clinically significant 
abnormal findings at following visits will be recorded in the source data and on the AE page in 
the eCRF. 
The following laboratory parameters will be measured (Table 2): 
 
Table 2 
Laboratory parameters  
 
Category 
Laboratory Parameter 
Haematology 
haemoglobin, white blood cell count including differential cell 
count, red blood cell count, platelet count, coagulation (partial 
thromboplastin time and prothrombin time) 
Clinical Chemistry 
(blood serum) 
Glucose (random), creatinine, total bilirubin, gamma-
glutamyltransferase (GGT), alanine aminotransferase (ALAT), 
aspartate aminotransferase (ASAT), Electrolytes (Na, K,), lactate 
dehydrogenase (LDH), total cholesterol 
Urinalysis 
blood, ketones, glucose, protein, pH, nitrites, leucocytes, 
microscopy if results are positive for blood or protein 
Serology (at Screening visits 
only) 
Hepatitis B (HBsAg, HB core antibody), hepatitis C, and HIV 
(anti-HIV). 
 
10.4.6 Local tolerability 
At each visit, the investigator will assess the local tolerability using a 4-point local tolerability / 
safety assessment scale (Table 3).  
Local Tolerability will be reported as an AE if the local tolerability signs and/or symptoms results 
in temporarily or permanently stopping of further administration of trial treatment or if it is 
stopped at the request of the subject. 
The outcome will have to be followed until resolution, steady state or until evidence that the 
investigational products and/or the subject’s participation in the trial are not responsible for 
the event. 


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Table 3 
Local skin tolerance/ side effects 
 
ERYTHEMA   
SCORE 
GRADE 
DESCRIPTION 
0 
1 
2 
3 
None 
Mild 
Moderate 
Severe 
No evidence of erythema present 
Slight pink discoloration 
Definite redness, easily recognized 
Marked erythema, bright red to dusky dark red in color  
HAEMATOMA 
SCORE 
GRADE 
DESCRIPTION 
0 
1 
2 
3 
None 
Mild 
Moderate 
Severe 
No haematoma 
Slight haematoma inside the treatment area 
Definite haematoma of strong color inside the treatment area  
Marked haematoma, covering the whole treatment area  
DYSPIGMENTATION (HYPER- AND HYPOPIGMENTATION) 
SCORE 
GRADE 
DESCRIPTION 
0 
1 
2 
3 
None 
Mild 
Moderate 
 Severe 
No signs of dyspigmentation 
Slight dyspigmentation of small definite area  
Marked dyspigmentation inside the treatment area  
 Dyspigmentation of the treatment area including areas not injected  
INDURATION 
SCORE 
GRADE 
DESCRIPTION 
0 
1 
2 
3 
None 
Mild 
Moderate 
 Severe 
No induration 
Barely perceptible induration  
Induration palpable  
   Marked induration 
PAIN/ DISCOMFORT 
SCORE 
GRADE 
DESCRIPTION 
0 
1 
2 
3 
None 
Mild 
Moderate 
Severe 
No pain or discomfort 
Slight pain, not really bothersome 
Definite pain that is somewhat bothersome 
Intense pain that may interrupt daily activities and/or pain 
Strong paraesthesia of the treatment area 
 
For subjective scoring, the subject should be questioned with regard to the period after the last 
and prior to the next injection procedures scheduled for the respective day. 
 
 Procedures 
10.5.1 Screening period (Day -21 to -1) 
Within the three weeks prior to the first visit, the volunteers will come to the sites for the initial 
screening (including documentation of demographic data). Screening assessments will be 
performed after the volunteer has agreed to participate and has signed and dated the informed 
consent form.  
The following examinations will be performed: 
• Documentation of relevant relevant medical and surgical history (last 1 year)  
• Documentation of demographic data; 
• Documentation of relevant previous medication (last 12 months); 
• Check in-/exclusion criteria (see section 8.2 and 8.4); 
• Physical examination of general appearance, mouth and throat, ears (left and right), lungs, 
abdomen, neurological (see section 10.4.3); 


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• Vital signs: systolic and diastolic blood pressure (mmHg), heart rate (beats per minute), and 
body temperature (see section10.4.4); 
• Blood and urine sampling for assessment of safety laboratory parameters, HIV/hepatitis; 
• Determination of treatment areas; 
• Marking of test areas; 
• Shaving of test areas; 
• Tatooing of test area; 
10.5.2 Experimental phase 
Visit 1 
• Re-check of the inclusion and exclusion criteria (see section 8.2 and 8.4); 
• Physical examination (see section 10.4.3); 
• Vital signs (see section 10.4.4); 
• Documentation of demographic data; 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Identification of treatment areas; 
• Marking of test areas; 
• Shaving of test areas; 
• TrichoScan imaging without hair dye; 
• Safety assessment and local tolerance assessment (see section 10.4); 
 
Visit 2 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs (record potential AEs also 15 min after first application); 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Randomisation 
• Identification of selected treatment areas; 
• Marking of selected treatment areas; 
• TrichoScan imaging including hair dye 
• IP application 
 
Visit 3 - 21 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Optinal: repeat of tattooing, if necessary; 
• Identification of selected treatment areas; 
• IP application 


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Visit 22 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Identification of selected treatment areas; 
• IP application 
 
Visit 23 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Identification of selected treatment areas; 
• Marking of selected treatment areas; 
• Shaving ot test areas 
• TrichoScan Image without hair dye 
 
Visit 24 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Identification of selected treatment areas; 
• Marking of selected treatment areas; 
• TrichoScan imaging including hair dye 
• IP application 
 
Visit 25 - 36 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Optinal: repeat of tattooing, if necessary; 
• Identification of selected treatment areas; 
• IP application 
 
 
Visit 37 
• Update of previous and concomitant medication; 
• Recording of AEs/SAEs; 


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• Safety assessment and local tolerance assessment (see section 10.4); 
• Identification of selected treatment areas 
• Shaving ot test areas; 
• TrichoScan imaging without hair dye; 
 
Visit 38 
• Update of previous and concomitant medication; 
• Physical examination (see section 10.4.3); 
• Vital signs (see section 10.4.4); 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Blood and urine sampling for assessment of safety laboratory parameters; 
• TrichoScan imaging including hair dye 
 
EoT visit (if not identical with Visit 38 due to early discontinuation) 
• Update of previous and concomitant medication; 
• Physical examination (see section 10.4.3); 
• Vital signs (see section 10.4.4); 
• Recording of AEs/SAEs; 
• Safety assessment and local tolerance assessment (see section 10.4); 
• Blood and urine sampling for assessment of safety laboratory parameters; 
 
Subjects should refer to the clinical site three times a week at an interval of at least 1 day. 
 Criteria for discontinuation of subject due to local intolerance and further 
proceedings 
In case of adverse events, which bring the subject at risk or might confound the results of the 
trial the subject should be discontinued. The subject should be referred to his private 
practitioner for further diagnostics. 
 
 


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11 ADVERSE EVENTS 
 Definitions 
11.1.1 Adverse Event 
Any untoward medical occurrence in a subject or clinical trial subject administered a medicinal 
product and which does not necessarily have a causal relationship with this treatment. 
Comment: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not considered related to the investigational 
medicinal product. 
11.1.2 Adverse Reaction 
All untoward and unintended responses to an investigational medicinal product related to any 
dose administered. 
Comment: All AEs judged by either the reporting Investigator or the Sponsor as having a 
reasonable causal relationship to a medicinal product qualify as adverse reactions. The 
expression reasonable causal relationship means to convey in general that there is evidence 
or argument to suggest a causal relationship. 
11.1.3 Unexpected Adverse Reaction 
An adverse reaction, the nature or severity of which is not consistent with the applicable 
product information (e.g. IB for an unauthorised IP or summary of product characteristics for 
an authorised product). 
Comment: When the outcome of the adverse reaction is not consistent with the applicable 
product information this adverse reaction should be considered as unexpected. 
11.1.4 Serious Adverse Event 
Any untoward medicinal occurrence or effect that at any dose: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalisation or prolongation of existing hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
• 
May not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed in the definition above. 
 
Comments: Life-threatening in the definition of an SAE or serious adverse reaction refers to 
an event in which the subject was at risk of death at the time of event; it does not refer to an 
event which hypothetically might have caused death if it was more severe. 
Medical judgement should be exercised in deciding whether an AE/reaction is serious in other 
situations. Important AEs/reactions that are not immediately life-threatening or do not result in 
death or hospitalisation but may jeopardise the subject or may require intervention to prevent 
one of the other outcomes listed in the definition above, should also be considered serious. 


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 Reporting of Adverse Events 
All trial subjects will be carefully monitored for the occurrence of AEs during the trial period, 
from intake of the first dose of IP until the last dose of IP for each subject. Previously reported 
AEs will be followed up and assessed as “recovered” or “not recovered”. The Investigator will 
collect AEs with a non-leading question such as “have you experienced any new health 
problems or worsening of existing conditions” as well as reporting events directly observed or 
spontaneously volunteered by subjects. 
Clearly related signs, symptoms and abnormal diagnostic procedure results should be grouped 
together and reported as a single diagnosis or syndrome whenever possible. 
All AEs including but not limited to events reported by the subject, or reported in answer to an 
open question by the Investigator or member of this team, which fall into any of the above 
definitions must be recorded as an AE in the source data and the eCRF and should include 
the following information: 
• 
Brief description of the event (diagnosis) 
• 
Start date (and time, if relevant) 
• 
Stop date (and time, if relevant) (or resolution) 
• 
Severity 
• 
Action taken regarding trial treatment 
• 
Opinion on causality 
• 
Seriousness 
• 
Outcome 
Severity 
Severity describes the intensity of an event, and will be assessed as: 
Mild 
The AE does not interfere in a significant manner with the subject’s normal functioning level. It 
may be an annoyance. 
Moderate 
The AE produces some impairment of function but not hazardous to health. It is uncomfortable 
and/or an embarrassment. 
Severe 
The AE produces significant impairment of functioning or incapacitation and/or it is a hazard 
to the subject. 
If an AE changes in severity, the worst severity should be reported. 
Causality 
Causality will be assessed as: 
Probable 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the drug, unlikely to be attributed to concurrent disease or other drugs or 


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chemicals, and which follows a clinically reasonable response on withdrawal (de-challenge). 
Re-challenge information is not required to fulfil this definition. 
Possible 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the drug, but which could also be explained by concurrent disease or other 
drugs or chemicals. Information on drug withdrawal may be lacking or unclear. 
Unlikely 
A clinical event, including laboratory test abnormality, with a temporal relationship to drug 
administration which makes a causal relationship improbable, and in which other drugs, 
chemicals or underlying disease provide plausible explanations. 
Follow-up of Subjects after Adverse Events 
Ongoing AEs will not be followed after the date of trial termination for a subject, unless the 
Investigator assesses the AE as relevant to follow from a trial perspective. The date when the 
Investigator considers one of these outcomes to have occurred for the last ongoing AE for a 
subject will be considered the last visit for this subject, and the outcome should be recorded in 
the source data and the eCRF. 
Abnormal Laboratory Values/Vital Signs 
An asymptomatic abnormal laboratory/vital sign finding should only be reported as an AE if it 
is clinically significant, if it fulfils the criteria for an SAE or if it causes the subject to discontinue 
the trial. 
Clinically significant abnormal findings at Visit 1 will be recorded in the source data and on the 
medical and surgical history page in the eCRF. New or worsening clinically significant 
abnormal findings at all Visits will be recorded in the source data and on the AE page in the 
eCRF. 
If an abnormal laboratory/vital sign value is associated with clinical signs and symptoms, the 
sign/symptom should be reported as an AE and the associated laboratory/vital sign result 
should be considered additional information. 
 Reporting of Serious Adverse Events 
The Investigator is responsible for ensuring that all SAEs are reported immediately, by e-mail 
(preferred) or fax, but in any case no later than 24 hours of any site staff becoming aware of 
the event.  
Initial notification should be followed as soon as possible by detailed written reports. The initial 
and follow-up reports should identify subjects by unique code numbers assigned in the trial 
and not by the subjects’ names, personal identification numbers, and/or addresses. The 
following information is mandatory for the initial report: 
• 
Subject trial identification data (ID) 
• 
Trial treatment (blinded, if applicable) 
• 
Start date (time, if relevant) of the trial treatment 
• 
Brief description of the event (diagnosis) 
• 
Start date (time, if relevant) of the event 
• 
Seriousness criteria 


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• 
Causality assessment 
For reported deaths, the Investigator should supply the Sponsor and the IEC (if applicable) 
with any additional requested information (e.g. autopsy reports and terminal medical reports). 
SAE REPORTING CONTACT DETAILS 
Dr. Monika Storm  
FGK Drug Safety 
E-mail:  
safety@fgk-cro.com 
FAX:  
 
+49 89 893 119 180  
In addition please notify the bioskin CTM (Anke Müller, anke.mueller@bioskin CRO.com). The 
FGK pharmacovigilance team takes over the Sponsor’s task of  informing the Competent 
Authorities and the European Medicines Agency (EMA) of any individual case reports of SAEs 
that are determined to be reportable by the sponsor (i.e. adverse events considered as serious, 
related and unexpected [SUSARs]). SUSARs will be distributed within 7/15 working days to 
the EMA (EudraVigilance) and concerned Competent Authorities and the Ethics Committees, 
according to local regulations. The investigator will be notified by FGK of safety 
issues/SUSARs according to current legislation. 
 Precautions/Overdose 
Since all study treatments are administered by trained trial personnel and are applied 
intradermally, the risk of overdose is minimal.  
 Pregnancy 
Not applicable. 


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12 STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
 Statistical and Analytical Plans 
Before unblinding the trial data, a separate statistical analysis plan (SAP), may be prepared. 
12.1.1 Data Sets to be Analysed 
The subject population sets are defined as follows: 
Safety analysis set (SAS): All randomised subjects who received at least 1 dose of IP. 
Subjects will be analysed according to actual treatment received. 
Full analysis set (FAS): All correctly included (i.e. fulfilling all the entry criteria) and 
randomised subjects with at least one post baseline measurement of the primary efficacy 
variable and having received at least one dose of the study medication. Subjects will be 
analysed according to the randomised treatment irrespective of actual treatment received.  
Per-protocol set (PPS): All subjects included in the FAS and who have: 
• 
taken the correct treatment throughout the trial (single treatment errors will be 
evaluated individually prior to un-blinding) 
• 
no major protocol violations that could interfere with the objectives of this trial. 
 
Further exclusion of subjects and/or subject data will be decided upon during the blind review 
of the data, focusing on concomitant medication and also considering compliance.  
The decisions regarding inclusion/exclusion of subjects and/or subject data from the trial 
analysis sets will be documented (on an individual level) at the clean file meeting before 
breaking the randomisation code. 
Safety summaries will be performed on the safety analysis set. The safety analysis set will be 
considered the primary analysis population for the safety variables. 
The PPS will be considered the primary efficacy subset of subjects. The FAS will be used for 
a sensitivity analysis of the primary efficacy variable only. 
12.1.2 Definitions 
Baseline 
A baseline measurement refers to the last non-missing assessment made 
before the first administration of IP (at the screening and baseline visit). This is 
valid where a change from baseline is derived. 
12.1.3 Statistical Issues 
Handling of dropouts and missing data 
Outliers will be included in summary tables and listings, and will not be handled separately. If 
a subject is withdrawn from the trial, all data collected until the time of withdrawal will be used 
in the analyses. Missing data will not be imputed. 
Level of significance, multiple comparisons and multiplicity 
Since this is an exploratory trial no formal hypotheses are postulated. Comparisons by means 
of p-values will be interpreted in a descriptive manner, nominal p-values and confidence 
intervals will be presented.  


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12.1.4 Summary Statistics 
Data will be summarised by means of summary statistics. Continuous data will be presented 
with the number of observations, mean value, standard deviation, minimum median and 
maximum value. Categorical data will be presented as counts and percentages. The data will 
be presented for each dose level. 
Descriptive summaries by study center will be presented for the primary efficacy endpoint only. 
12.1.5 Efficacy Analyses 
The primary efficacy objective is to evaluate the hair density (No. of hairs per cm2) on the 
scalp after 12 weeks of treatment as compared to baseline. The relative change will be used, 
i.e. after 12 weeks of − Baseline 
The hypothesis that the relative change from baseline is equal to zero will be analysed using 
the exact Wilcoxon signed rank test. 
The secondary efficacy objectives will be analysed using the same methodology as in the 
analysis of the primary efficacy objective. 
 
12.1.6 Demographic and Other Baseline Characteristics 
Demographic and other baseline data will be presented using summary statistics. 
12.1.7 Exposure to Treatment 
Exposure to treatment (number of injections divided by planned number of injections) with IP 
will be presented using summary statistics for each dose. 
12.1.8 Prior and Concomitant Treatment 
Prior and Concomitant medication will be summarised as number of subjects being treated 
with each type of medication/therapy classified according to Anatomical Therapeutic Chemical 
(ATC) level 3 and World Health Organization (WHO) Drug Dictionary preferred term.  
12.1.9 Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and 
tabulated by system organ class (SOC) and by preferred term.  
The total number of subjects with at least 1 AE, at least one treatment emergent AE (TEAE) 
and the total number of AEs and TEAEs will be presented. 
The number of subjects, percentage and the number of TEAEs will be tabulated by SOC and 
by preferred term. TEAEs will also be tabulated by severity and by relationship to treatment. 
In this table, subjects with TEAEs will be counted only once within a SOC or a preferred term 
by using the event with the worst severity or the closest causal relationship, respectively, within 
each category. AEs due to local tolerance issues will be presented by dose administered to 
the respective treatment areas. 
12.1.10 
Medical History 
All previous and concomitant diseases will be coded with MedDRA. 


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12.1.11 
Other Safety Assessments 
Physical Examination 
Physical examination will be presented in a shift table. The shift table will show the number of 
subjects who changed (compared to visit 1) from “normal” or “abnormal” at baseline to “normal” 
or “abnormal” at each time of assessment. 
Vital Signs 
Vital signs will be summarised by treatment combination, together with changes from baseline, 
by visit. 
Laboratory Safety Assessments 
For laboratory data, summary statistics will be produced for observed values and for changes 
from baseline to each visit. In addition, the number of abnormal and clinically significant 
observations will be tabulated for each treatment combination by visit. Abnormal values will be 
flagged in listings.  
Shift tables will show the number of subjects who changed from below, within or above the 
reference range at baseline to below, within or above the reference range at each time of 
assessment.  
For laboratory values which are below the limit of quantification, the value corresponding to 
the limit of quantification will be used when summarising data (e.g. if the result is <x.x then the 
value x.x will be used in the statistical analysis). 
Local Tolerance Assessments 
Local tolerance assessments will be summarised by dose administered to the respective 
treatment areas. 
 Determination of Sample Size 
The change from baseline until end of the treatment period (delta) is the primary efficacy 
endpoint and the base for the sample size estimation. 
The expected standard deviation for delta is 23.0 based on data published by Olsen EA et. al 
[12]. The expected change in hair density from baseline is 8 % which is 13.6 hairs/cm2 
assuming the baseline hair density is 170 hairs/cm2. 
Using a statistical power of 80 % and a two-sided significance level on 5 % the number of 
fully evaluable subject on the dose of interest is 23. Assuming a dropout rate of 10 % results 
in a need to include 26 subjects whom all are given the dose of interest. 
 
Justification for the sample size 
12.3.1 
Introduction 
The assumptions for the design and power calculations are: 
• 
The variable the powering is based on is Hair Density (HD, number of hair per cm2) 
and absolute change from baseline 
• 
The hypotheses to be tested will be two-sided, i.e. no assumptions on the direction of 
the effect 
• 
The estimation of the expected baseline hair density and expected standard deviation 
is based on the Olsen EA et. al [12] 


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12.3.2 
Expected baseline hair density and expected standard deviation 
The expected baseline hair density is presented in Table 1 in Olsen EA et. al [12]. In the 
patients randomised to get placebo the mean hair density is 168.9 hairs/cm2 and in the 
patients randomised to receive active treatment the baseline hair density is 170.8 hairs/cm2. 
In the sample size calculations it is then estimated that the mean hair density at baseline is 
170 hairs/cm2. 
The minimum increase in hair density expected to be needed from a marketing perspective is 
8%, i.e. a mean increase of 13.6 hairs/cm2. In the sample size calculations an increase of 
13.0 is used in order to be conservative. 
In Table II in Olsen EA et. al [12] the observed standard deviation for the change in hair 
density from baseline until 16 weeks post baseline is given. The observed standard deviation 
for patients given placebo is 19.7 and for patients given active treatment it is 22.5. In the 
sample size calculations a standard deviation of 23.0 is used in order to be conservative. 
12.3.3 
Sample size Formula 
The following hypothesis is to be tested: 
H0: μ = 0 
H1: μ ≠ 0 
Where μ is the expected value in the group (i.e. the mean in an infinite group) implying that μ 
is the expected absolute change over time within a certain dose level. 
The following formula has been used to calculate the number of patients needed [13] 
(n=number of patients on the dose of interest): 
n =
σ2 × ൫𝜆𝜆𝛼𝛼+ 𝜆𝜆𝛽𝛽൯
2
(µ)2
 
In the formula above σ is the expected standard deviation, λα is the 1−α percentile of the 
standardized normal distribution and λβ is the 1−β percentile of the standardized normal 
distribution. If the test is two-sided and the significance level is 0.0500 then λα = 1.9600. If 
the power is 80% then λβ = 0.8416 and if the power is 90% then λβ = 1.2816. 
12.3.4 
Results 
Table 4 
Number of fully evaluable subjects needed in order to get 80 % 
probability to get a two-sided p-value less than 5 % by some values for 
the expected standard deviation and by some differences in hair counts 
from baseline until end of treatment. 
 
Delta 
Standard deviation 
18.00 
19.00 
19.70 
20.00 
21.00 
22.00 
22.50 
23.00 
24.00 
25.00 
10.00 
26 
29 
31 
32 
35 
38 
40 
42 
46 
50 
11.00 
22 
24 
26 
26 
29 
32 
33 
35 
38 
41 
12.00 
18 
20 
22 
22 
25 
27 
28 
29 
32 
35 
13.00 
16 
17 
19 
19 
21 
23 
24 
25 
27 
30 
13.60 
14 
16 
17 
17 
19 
21 
22 
23 
25 
27 
14.00 
13 
15 
16 
17 
18 
20 
21 
22 
24 
26 
15.00 
12 
13 
14 
14 
16 
17 
18 
19 
21 
22 
16.00 
10 
12 
12 
13 
14 
15 
16 
17 
18 
20 
 


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 Procedures for Reporting any Deviation(s) from the Original Statistical Analysis 
Plan 
Any important deviation(s) from the originally planned statistical analysis (as described in the 
trial protocol) will be described and justified in a protocol amendment, in the statistical analysis 
plan and/or in the final report, as appropriate. 


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13 INVESTIGATOR/SPONSOR RESPONSIBILITIES 
 Ethics 
13.1.1 Independent Ethics Committee (IEC) 
This protocol and any amendments will be submitted to a properly constituted EC, in 
accordance with the International Conference on Harmonisation (ICH) guidelines, the 
applicable European Directives and local legal requirements, for approval/favourable opinion 
of the trial. Approval/favourable opinion must be obtained in written form before the first subject 
can be recruited. 
13.1.2 Ethical Conduct of the Trial 
The trial will be conducted in compliance with the protocol, regulatory requirements, good 
clinical practice (GCP) and the ethical principles of the latest revision of the Declaration of 
Helsinki as adopted by the World Medical Association. 
13.1.3 Subject Information and Consent 
All subjects will receive written and verbal information regarding the trial before any trial-related 
procedures are performed. This information will emphasise that participation in the trial is 
voluntary and that the subject may withdraw from the trial at any time and for any reason. All 
subjects will be given the opportunity to ask questions about the trial and will be given sufficient 
time to decide whether to participate in the trial. 
Informed consent must be obtained before any trial-related procedures at screening visit.  
The following will thus be required for participation in the present trial: 
Subjects ≥18 years: informed consent form signed and personally dated by the subject  
and by the person who conducted the informed consent discussion 
The consent includes information that data will be recorded, collected, processed and may be 
transferred to European Economic Area (EEA) or non-EEA countries. In accordance with the 
European Union Data Protection Directive (95/46/EC), the data will not identify any persons 
taking part in the trial. 
A copy of the subject information including the signed informed consent form will be provided 
to the subject, for their records. 
 Regulatory Authority 
This protocol and any amendments will be submitted to the responsible regulatory authority 
for approval of the trial. Approval must be obtained in written form before the first subject can 
be recruited. 
 Subject Data Protection 
All information containing personal data will be handled in accordance with German data 
protection legislation and with the EU Data Protection Directive (95/46/EC). 


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 Other Ethical and Regulatory Issues 
If a significant safety issue is identified, either from an individual case report or review of 
aggregate data, then the Sponsor will issue prompt notification to all parties: Regulatory 
Authorities, Investigators and ECs. 
A significant safety issue is one that has a significant impact on the course of the clinical trial 
or program (including the potential for suspension of the trial program or amendments to 
protocols) or warrants immediate update of informed consent. 
 Good Clinical Practice 
13.5.1 Legal Preconditions 
This clinical trial is carried out according to the current and valid guidelines of and in 
agreement with: 
• 
ICH efficacy guidelines and “Guidelines for Good Clinical Practice” (GCP) (2002) 
• 
Declaration of Helsinki, revised 2013; 
• 
Statute in dealing with pharmaceuticals, German drug law (AMG), in version of 
12.12.2005, Article 1 changed most recently on 02.09.2015 (BGBl. I S. 1571); 
• 
GCP-regulation: Decree in pursuance on Good Clinical Practice in conduction of 
human clinical drug trials from 09.08.2004, article 8 changed most recently on 
19.10.2012 (BGBl. I S. 2192); 
• 
Directive 2001/20/EG of the European parliament and of the council from 04.04.2001 
on the approximation of the laws, regulations and administrative provisions of the 
Member States relating to the implementation of good clinical practice in the conduct 
of clinical trials on medicinal products for human use; 
• 
Directive 2005/28/EG from 08.04.2005 laying down principles and detailed guidelines 
for good clinical practice as regards investigational medicinal products for human use, 
as well as the requirements for authorization of the manufacturing or importation of 
such products; 
• 
ENTR/F2/BL D (2003): Detailed guidance for the request for authorization of a clinical 
trial on a medicinal product for human use to the competent authorities, notification of 
substantial amendments and declaration of the end of the trial (October 2005); 
• 
ENTR/CT 2: Detailed guidance on the application format and documentation to be 
submitted in an application for an Ethics Committee opinion on the clinical trial on 
medicinal products for human use (February 2006). 
13.5.2 Protocol conformity 
Protocol deviations are any discrepancy from the procedures defined in the trial protocol, such 
as skipping tests or examinations, not permitted concomitant medication, improper handling of 
the investigational product(s). After inclusion of a subject, it is the responsibility of the 
investigator/sponsor to avoid protocol deviations.  
Deviations from the protocol will be assessed as “minor” or “major” on a case-by-case basis in 
cooperation with the Sponsor. This assessment will take place during a blind data review 
meeting. Major deviations from the protocol will lead to the exclusion of a subject from the per 
protocol analysis set.  


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Protocol deviations are specified in the ‘Deviation Definition Document’. The Investigator 
shall make best efforts to collect the data exactly as specified in the protocol. Nevertheless 
small discrepancies can occur. These differences are to be noted and explained properly. 
 Subject Records and Source Data 
Some data may be recorded directly in the eCRF and will then be considered source data. 
These data may include, but are not limited to, the following: 
• 
height 
• 
weight 
• 
sex 
• 
race 
It is the responsibility of the Investigator to record essential information in the medical records 
in accordance with national regulations and requirements. The following information should be 
included as a minimum: 
• 
A statement that the subject is in a clinical trial 
• 
The identity of the trial e.g. Trial code 
• 
Subject screening number and/or subject number 
• 
That informed consent was obtained and the date 
• 
Diagnosis 
• 
Dates of all visits during the trial period 
• 
Any information relating to AEs 
• 
All treatments and medications prescribed/administered (including dosage) 
• 
Date of trial termination 
• 
Subject health service identification number 
The Investigator is responsible for ensuring the accuracy, completeness, legibility and 
timeliness of the data recorded in the source data and the eCRFs. Data reported in the eCRF 
that are derived from source documents should be consistent with the source documents or 
the discrepancies should be explained. Completed sections of eCRFs will be monitored on a 
regular basis as defined in the monitoring plan / monitoring manual. 
 Access to Source Data and Documentation 
The Investigator should guarantee access to source documents for the monitor and auditors 
as well as for inspection by appropriate regulatory agencies, and the EC, if required. 
 Monitoring 
The monitor will visit the trial sites before, during and after the trial to ensure that the trial is 
conducted and documented in accordance with this protocol, ICH-GCP guidelines, regulatory 
requirements and any trial specific documents such as eCRF completion guidelines. 
Monitoring visits will be conducted to confirm that e.g.: 


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• 
The rights and well-being of human subjects are protected 
• 
The investigational team is adhering to the trial protocol 
• 
Informed consent has been obtained from all participants 
• 
AEs have been reported as required 
• 
Data are being accurately recorded in the eCRFs and are in accordance with source 
data 
• 
IP is being stored correctly and drug accountability is being performed on an on-going 
basis 
• 
IP is given to correct subject 
• 
Facilities are, and remain, acceptable throughout the trial 
• 
The Investigator and the site are receiving sufficient information and support throughout 
the trial 
The eCRF data will be monitored on regular intervals. The monitoring will include source data 
verification (SDV) according to the SDV list and verification of data consistency over time. The 
Investigator and other relevant trial personnel should be available during the monitoring visits. 
 Data Management 
An electronic CRF system will be used to capture data from the trial. The Investigator agrees 
to maintain accurate eCRF and source documentation as part of the research under this 
protocol. Each completed eCRF must be reviewed by the Investigator in a timely manner. Data 
management and handling of data will be conducted according to the trial specific Data 
Management Plan in accordance with ICH guidelines and the CROs standard operating 
procedures (SOPs). 
Data entry will be performed by the trial site personnel. Validation and data queries will be 
handled by the CROs Data Management Team. The data will be subjected to validation 
according to the CROs SOPs in order to ensure accuracy in the collected eCRF data. 
Changes to eCRF (if used) will be made at the site by the trial site personnel. The eCRF will 
have an audit trail with appropriate functionality for data capture, tracking and documentation 
of any queries or changes. Once all the queries are closed and data have been verified by the 
CRA, the eCRF will be signed (E-Signature) by the investigator and the database will be 
locked. 
Before database closure, a reconciliation will be performed between the SAEs entered in the 
safety database and the trial database. After database closure, the database will be exported 
as SAS® data sets. 
 Quality Assurance and Audit 
Audits or inspections, including source data verification, may be performed by the sponsor or 
its representatives, a CA and/or an EC. 
 Record Retention 
The Investigator/institution should maintain essential documents for 15 years (as defined in 
ICH E6 GCP, Section 8) as required by the applicable regulatory requirement(s). 


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The Investigator/institution should take measures to prevent accidental or premature 
destruction of the documents. 
Essential documents should be retained according to applicable regulatory requirements of 
the country(ies) where the product is approved, and/or where the Sponsor intends to apply for 
approval. 
It is the responsibility of the Sponsor to inform the Investigator/institution in writing as to when 
the documents no longer need to be retained. 
 Insurance 
Every subject participating in the clinical trial will be insured in accordance with § 40 
paragraph 3 of the German drug law against injuries to health which may occur during the 
trial. 
Excluded from this however are injuries to health and deteriorations of illnesses already in 
existence which would have occurred or continued to exist even if the subject had not taken 
part in the clinical trial. 
The insurance cover is jeopardized if the subject fails to report immediately to the 
investigator or responsible physician any injury to health which might have resulted from 
participation in the clinical trial, or if he/she undergoes any other medical treatment without 
their consent before the clinical trial has been completely finished - insofar as the individual 
subject is concerned. 
Any injury to health which might have occurred as a result of participation in the clinical trial 
must be reported by the subject to the insurer without delay. The investigator is obliged to 
make such a report in any case. 
The subject insurance will be arranged by bioskin GmbH on the basis of the final version of 
the subject information and informed consent form. The subject insurer is HDI-Gerling 
Industrie Versicherung AG”, Überseering 10a, 22297 Hamburg, Tel. 040/36150-257, Fax 
0511/645-1152305.  
 
A travel insurance for the way to and from the site will be arranged. 
 Report and Publication 
After completion of the trial, a clinical trial report will be prepared according to the ICH Guideline 
for Structure and Content of Clinical Trial Reports (ICH E3) by the Sponsor, to be defined in 
close collaboration with the Investigator and the Sponsor. 
All publications and presentations must be based upon the clinical trial report.  
All information supplied by the Sponsor in connection with this trial will remain the sole property 
of the Sponsor and is to be considered confidential information. No confidential information will 
be disclosed to others without obtaining prior written consent from the Sponsor and will not be 
used except in the performance of this trial. 
If an Investigator wishes to publish results from this clinical trial, written permission to publish 
must be obtained from the Sponsor in advance. As some of the information regarding the IP 
and development activities at the Sponsor may be of a strictly confidential nature, the Sponsor 
must first review any publication manuscript prior to their submission to journals, meetings or 
conferences. 
The Sponsor may choose to publish or present data from this trial. If an Investigator is offered 
authorship, he/she will be asked to critically review the article for important intellectual content 
and approve the version to be published. The Sponsor has the right to use the results for 
registration and internal presentation and for promotion of the Sponsor’s commercial interests. 


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14 REFERENCE LIST 
1. 
Hamilton JB. Patterned loss of hair in man: Types and incidence. Ann N Y Acad Sci. 
1951;53:708–28. 
2. 
Fitzpatrick, T.B., The validity and practicality of sun-reactive skin types I through VI. 
Arch Dermatol, 1988. 124(6): p. 869-71. 
3. 
Paus, R. and G. Cotsarelis, The biology of hair follicles. N Engl J Med, 1999. 341(7): 
p. 491-7. 
4. 
Vogt, A., K.J. McElwee, and U. Blume-Peytavi, Biology of the hair follicle, in Hair 
Growth and Disorders, U. Blume-Peytavi, D.A. Whiting, and R.M. Trüeb, Editors. 
2008. 
5. 
Yu, D.W., et al., Osteopontin gene is expressed in the dermal papilla of pelage 
follicles in a hair-cycle-dependent manner. J Invest Dermatol, 2001. 117(6): p. 1554-
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Holmqvist H, (2016a), “Summary Report: Detection of FOL peptide in mouse skin 
after subcutaneous injection.” ImaGene-iT-SR (1) 
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Holmqvist H, (2016b), “Summary Report: Blocking of FOL005 peptide binding in 
human skin tissue.” ImaGene-iT-SR (2) 
8. 
Edman K, (2017), “A randomised, double-blind, placebo-controlled trial of FOL-005 to 
investigate clinical safety and effect on hair growth in healthy volunteers.” Draft Trial 
Report FCS-001 
9. 
Hoffmann R TrichoScan: Ein neues Werkzeug für die digitale Haarzählung. 
HAUTARZT. Dez 2002; 53:798-804  
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Hoffmann R TrichoScan: combining epiluminescence microscopy with digital image 
analysis for the measurement of hair growth in vivo. European Journal of 
Dermatology. Jul-Aug 2001; 4(11) 362-368 
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Alpert, B., et al., Recommendations for blood pressure measurement in human and 
experimental animals; part 1: blood pressure measurement in humans. Hypertension, 
2006. 48(1): p. e3; author reply e5. 
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Elise A. Olsen, David Whiting, Wilma Bergfeld, Jeffrey Miller, Maria Hordinsky, Rita 
Wanser, Zhang and Bruce Kohut: “A multicenter, randomized, placebo-controlled, 
double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus 
placebo in the treatment of androgenetic alopecia in men”. American Academy of 
Dermatology, Inc., 2007. 
13. 
Lachin John M: Introduction to sample size determination and power analysis for 
clinical trials. Controlled Clinical Trials 2, 93-113, 1981. 
  
 


Sponsor: Follicum AB 
 
Clinical Trial Protocol 
Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
Final 
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15 SIGNATURE PAGES 
 
Declaration of Sponsor 
Title: A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to investigate 
efficacy on hair growth on scalp skin in healthy volunteers. 
 
This trial protocol was subjected to critical review. The information it contains is consistent 
with current knowledge of the risks and benefits of the investigational product, as well as with 
the moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki, revised 2013, and the guidelines on Good Clinical Practice (GCP). 
 
 
_____________________________________ 
_____________________ 
Jan Alenfall, PhD, CEO 
Follicum AB 
Date 
Scheelevägen 22 
Box 719 
SE-220 07 Lund 
Sweden 
Phone: 
+46 709 31 51 15 
E-Mail:  
jan.alenfall@follicum.com 
 
 
 
_____________________________________ 
_____________________ 
Johan Quensel, CEO 
Date 
Q Clinical Research Consulting AB 
Lärarvägen 12 
SE-247 45 Torna Hällestad 
Sweden 
Phone: 
+46 760 46 97 44 
E-Mail:  
johan.quensel@follicum.com 


Sponsor: Follicum AB 
 
Clinical Trial Protocol 
Protocol: FCS-002, version: 1.0 
 
CONFIDENTIAL 
 
Final 
56 of 58 
07 November 2017 
 
Declaration of the Coordinating Investigator 
Title: A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to investigate 
efficacy on hair growth on scalp skin in healthy volunteers. 
 
This trial protocol was subjected to critical review. The information it contains is consistent 
with current knowledge of the risks and benefits of the investigational product, as well as with 
the moral, ethical and scientific principles governing clinical research as set out in the 
Declaration of Helsinki, revised 2013, and the guidelines on Good Clinical Practice (GCP). 
 
 
 
_____________________________________ 
_____________________ 
Signature 
Date 
Prof. Dr. Ulrike Blume-Peytavi 


Sponsor: Follicum AB 
Clinical Trial Protocol
Protocol: FCS-002, version: 1.0 
CONFIDENTIAL
 
Final 
57 of 58 
07 November 2017 
 
Appendix 1 
Schematic IP Dilution Manual for the FOL-005 IMP 
Study Title: A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to 
investigate efficacy on hair growth on scalp skin in healthy volunteers 
Study Code: FCS-002 
EudraCT: 2017-003809-17 
IMP: FOL-005, 10 µg/mL, solution for injection, 9 mL 
Other material: All needed material is delivered to site by the sponsor. This includes sterile, 
labelled dilution vials, sterile diluent, sterile syringes and needles needed for handling the 
dilution. 
The dilution of IMP at site laboratory (or equivalent) is handled by personnel not otherwise 
involved in the study. A schematic description of the dilution of IMP in the clinical study is 
found below. 
Dilution vials are marked with a vial code. The vial code number is predetermined and 
random and will remain the same throughout the study.  
Please note that the order of the vial code numbers shown here are examples only and will 
be randomized and blinded in the study. 
Vial code 
X 
1 
2 
3 
4 
5 
FOL-005 (µg/mL) 
5 
2 
1 
0.5 
0.125 
Placebo 
Given dose per 50 µL 
injection (µg) 
- 
0.100 
0.050 
0.025 
0.00625 
- 
1) One vial, IMP (FOL-005, 10 µg/mL solution for injection) is thawed (precise thawing 
instruction will be provided) 
2) Mark each dilution vial with preparation number and subject ID(s). 
3) Equip each vial with a vented dispensing pin. 
4) To each dilution vial (vial code 1-5 and X) transfer 3 mL of diluent.  
5) Withdraw 3 mL from the thawed IMP and transfer to the vial marked “X”. Mix (precise 
mixing instruction will be provided) 
6) Withdraw 2 mL from the vial marked “X” and transfer to the vial marked “1”. Mix 
7) Withdraw 0.75 mL from the vial marked “X” and transfer to the vial marked “2”. Mix 
8) Withdraw 0.75 mL from the vial marked “2” and discard. 
9) Withdraw 2 mL from the vial marked “1”, discard 1 mL and transfer 1 mL to the vial 
marked “3”. Mix 
10) Withdraw 1 mL from the vial marked “3” and transfer to the vial marked “4”. Mix. 
11)  Withdraw 1 mL from the vial marked “4” and discard. 
12) Discard the vial marked “X”. 
Each vial now contains 3 ml, and is marked with a vial code (random order). The vials are 
prepared at the study site daily. At the study site the investigator injects 50 µL from each vial 
in accordance with the patient specific randomization schedule. 


Sponsor: Follicum AB 
Clinical Trial Protocol
Protocol: FCS-002, version: 1.0 
CONFIDENTIAL
 
Final 
 
07 November 2017 
 
Declaration of the Investigator 
Title: A randomised, double-blind, placebo-controlled phase 2 trial of FOL-005 to investigate 
efficacy on hair growth on scalp skin in healthy volunteers. 
 
All documentation for this trial that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this trial 
protocol, Investigator's Brochure, Case Report Forms (eCRFs), and other scientific data. 
The trial will not be commenced without the prior written approval/favourable opinion of a 
properly constituted Ethics Committee (EC) and the regulatory authority. No changes will be 
made to the trial protocol without the prior written approval of the Sponsor, the EC and the 
regulatory authority, except where necessary to eliminate an immediate hazard to the 
subjects. 
I have read and understood and agree to abide by all the conditions and instructions 
contained in this protocol. 
I confirm with my signature  
• 
that I agree to conduct the trial in accordance with local law, the Declaration of Helsinki, 
ICH-GCP. 
• 
that I have acquainted myself with the results of the pharmacological and toxicological 
trials of the investigational product and the results of other trials as described in the 
investigator’s brochure or other appropriate information. 
 
 
 
 
 
_____________________________________ 
_____________________ 
Signature 
Date 
 
_____________________________________ 
Name (block letters) 
 
_____________________________________ 
Title (block letters) 
 
_____________________________________ 
Institution (block letters) 
 
_____________________________________ 
Phone number