Study for the Evaluation of the Degree of Skin Satisfaction of Cosmetics Creams PB-011 and PB-012 for Sensitive Skin in Oncological Patients Affected by a Palmoplantar Polyneuropathy Secondary to Chemotherapy or Chemotherapeutic Agents' Fusion to Monoclonal Antibodies (Immunocitostatics)
Conditions: Quality of Life (QOL), CIPN - Chemotherapy-Induced Peripheral Neuropathy
Sponsor: PROSPERA BIOTECH S.L.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY TO EVALUATE THE DEGREE OF SKIN SATISFACTION WITH THE 
COSMETIC CREAMS FOR SENSITIVE SKIN PB-011 AND PB-012 IN 
ONCOLOGY PATIENTS WITH PALMOPLANTAR POLYNEUROPATHY 
SECONDARY TO TREATMENT WITH CHEMOTHERAPY OR 
CHEMOTHERAPEUTIC AGENTS FUSED TO MONOCLONAL 
ANTIBODIES (IMMUNOCYTOSTATIC). 

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Study code: 20PB-02 
Sponsor: Prospera Biotech S.L. 
 
 

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Study Protocol Compliance Form 
 
 
Ms. Marta García Escolano as Sponsor, has examined the Protocol nº 20PB-02, version: 1.5, 
Date: 28/07/2022, entitled:  
 
‘STUDY FOR THE EVALUATION OF THE DEGREE OF SKIN SATISFACTION OF THE COSMETIC 
CREAMS FOR SENSITIVE SKIN PB-011 AND PB-012 IN ONCOLOGICAL PATIENTS AFFECTED BY 
PALMOPLANTAR POLYNEUROPATHY SECONDARY TO TREATMENT WITH CHEMOTHERAPY OR 
CHEMOTHERAPEUTIC AGENTS FUSED TO MONOCLONAL ANTIBODIES 
(IMMUNOCYTOSTATIC)’. 
 
And agrees to conduct the study according to the guidelines of this protocol and to conform 
to its requirements, subject to its approved ethical and safety considerations.  
 
In Elche, 28th July 2022, 
 
 
Signed: Dr. Marta García Escolano 
 
 

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TABLE OF CONTENTS 
1. SUMMARY 
 
 
 
 
 
 
 
 
 
7 
2. GENERAL INFORMATION 
 
7 
2.1. Identification of the study 
 
7 
2.2. Type of study  
7 
2.3. Description of the product under study 
7 
2.4. Data relating to the sponsor 
 
8 
2.5. Identification of the persons responsible for monitoring 
8 
2.6. Details of the investigators 
 
8 
2.7 Sites where the study is being conducted and PIs 
 
9 
2.8. Expected duration of the study 
9 
3. INTRODUCTION 
 
9 
4. RATIONALE AND OBJECTIVES OF THE STUDY  
11 
4.1. Main objective 
 
11 
4.2. Secondary objective 
 
11 
5. TYPE OF STUDY AND STUDY DESIGN 
11 
5.1. Study development and design phase 
11 
5.2. Randomisation process 
 
11 
5.3. Masking 
 
11 
6. SUBJECT SELECTION  
12 
6.1. Inclusion criteria 
 
12 
6.2. Exclusion criteria 
 
12 
6.3. Number of intended subjects and justification  
13 
6.4. Duration of the recruitment period 
 
14 

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7. DESCRIPTION OF THE TEST PRODUCT 
14 
7.1. Study medication 
 
14 
7.2. Conduct of the study  
14 
7.3. Withdrawal criteria 
15 
8. TRIAL CONDUCT AND RESPONSE ASSESSMENT 
16 
8.1. Variables to be studied 
 
16 
8.2.  Collection of Variables 
16 
9. ADVERSE EVENTS 
 
17 
9.1. Detection and documentation of adverse events 
 
17 
9.2. Causality assessment  
18 
9.3. Procedures for immediate reporting of serious or unexpected events 
19 
10. ETHICAL ISSUES 
20 
10.1. General considerations 
 
20 
10.2. Information to volunteers 
20 
10.3. Confidentiality and Access to Data 
 
21 
10.4. Financial report 
 
21 
10.5. Insurance Policy 
 
21 
11. PRACTICAL CONSIDERATIONS 
 
22 
11.1. Responsibilities of all participants in the study 
22 
11.2. Deviations from the protocol  
22 
11.3. Collection and archiving of documentation 
 
22 
11.4. Amendments to the protocol  
23 
11.5. Investigator acceptance. 
23 
12. STATISTICAL ANALYSIS 
 
23 

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13. BIBLIOGRAPHY 
 
ANNEXES                                                        
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
25 

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1. SUMMARY 
A pilot controlled clinical study is proposed to evaluate and compare the degree of satisfaction 
and skin comfort with cosmetic creams PB-011 and PB-012 in oncology patients who have 
developed palmar and plantar peripheral poly-neuropathy due to treatment with chemotherapy 
or chemotherapeutic agents fused to monoclonal antibodies (immunocytostatic). Both products 
are cosmetic creams derived from the line Nocisens (for the care of sensitive skin with atopic 
tendency). The hypothesis to be tested is that care with PB-011 or PB-012 for sensitive skin 
associated with palmar and plantar peripheral poly-neuropathy in oncology patients will 
increase their degree of satisfaction and skin comfort. A parallel, randomised, double-blind, 
masked, double-blind study is proposed in patients who are about to start chemotherapeutic 
treatment. The study involves two populations: (i) the population where PB-011 cream will be 
tested; and, (ii) the population that will test PB-012 cream. The duration of the project will be 
12 months, and participants will have to apply the cream on their hands once a day during the 
period of chemotherapy treatment. A sample size of 60 volunteers per population has been 
estimated to ensure statistical significance. As a relevant qualitative variable for patients who 
have developed neuropathy, the degree of satisfaction and skin comfort will be assessed by 
means of a questionnaire.   
2. GENERAL INFORMATION 
2.1. Study identification 
Study code: 20PB-02 
Study title: ‘Study for the evaluation of the degree of skin satisfaction of the cosmetic creams 
for sensitive skin PB-011 and PB-012 in oncology patients with palmoplantar polyneuropathy 
secondary to treatment with chemotherapy or chemotherapeutic agents fused to monoclonal 
antibodies (immunocytostatic)’.    
2.2. Type of study  
 Multicentre, controlled, parallel, randomised, double-blind, masked, double-blind, randomised 
study. 
 
2.3. Description of the products under study 
 
Product: Cosmetic creams with Ref. PB-011 and PB-012 
Trade name: Nocisens. The formulation with the best acceptance in the study population will be 
marketed under the name Oncapsisens. 

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Commercial name: Prospera Biotech S.L 
Code and INCI:  
• 
PB-011: Capric Triglyceride, Glyceryl Behenate, Glyceryl Stearate, Hydrogenated Castor 
Oil, Diethylene Glycol Monoethyl Ether, Tocopherol, Hydroxymethoxyiodobenzyl 
Glycolamide Perlargonate. 
• 
PB-012: Capric Triglyceride, Glyceryl Behenate, Glyceryl Stearate, Hydrogenated Castor 
Oil, Diethylene Glycol Monoethyl Ether, Tocopherol. 
2.4. Data relating to the sponsor 
Dr. Marta García Escolano, 
Chief Executive Officer, Prospera Biotech S.L. 
Quorum III Building - Miguel Hernández University Science Park 
Av. de la Universidad s/n 
03202 Elche. 
 
2.5. Identification of the investigators responsible for monitoring  
• Dr. Pedro Zapater Hernández.  
Department of Pharmacology, Hospital General Universitario de Alicante.   
Email: pzapater@goumh.umh.es  
• Dra. Asia Fernández Carvajal.  
Institute of Research, Development and Innovation in Health Biotechnology of Elche (IDIBE)- 
Miguel Hernández University of Elche (UMH).  
Email: asia.fernandez@umh.es  
• 
Dra. Clotilde Ferrándiz Huertas, 
Chief Scientific Officer Prospera Biotech,  
Email: cferrandiz@prosperabiotech.com 
2.6. Research data  
Principal Investigator 
• 
Dr... 
Deparment… 

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Hospital… 
Email:… 
Task: recruitment, follow-up and control of patients. Completion of data collection notebook. 
Final analysis and publication of the results. 
• 
Co-researchers 
 Name:… 
Department: … 
Email: … 
Task: follow-up and control of patients. Completion of data collection notebook 
2.7. Expected duration of the study           
The overall duration of the study is expected to be 12 months from the start of recruitment of 
the populations until the last follow-up control and analysis of the data generated.  
The intervention (application of the cosmetic cream) will take place from the beginning to the 
end of the chemotherapy treatment, with 1 daily application of the product (PB-011 or PB-012) 
on the hands. If sensory discomfort or, in the worst case, peripheral neuropathy develops during 
the period of chemotherapy or immunocytostatic treatment, the application shall be increased 
to twice daily on the affected areas (usually hands and feet). In case of lack of efficacy of the 
product, the investigator in charge may withdraw the subject from the study after three months 
of application of the product. 
3. INTRODUCCIÓN 
 
The impact of cancer in the western world and the growing number of people affected each 
year1 means that new, increasingly effective and selective treatments are appearing relatively 
quickly. However, although these treatments are highly effective in killing tumour cells, they are 
not their only target. Molecules used in cancer treatments often affect healthy cells, causing 
side effects (nausea, diarrhoea, anaemia, immunosuppression, fatigue and hair loss). When 
antineoplastic therapies affect the sensory peripheral nervous system, they can cause peripheral 
polyneuropathy (NP or CIPN (Chemotherapy-Induced Peripheral Neuropathy)). The prevalence 
of this disease varies depending on the chemotherapy agent administered, affecting up to 80% 
of patients treated with taxanes (paclitaxel and/or docetaxel) or up to 95% of patients treated 
with oxyplatin2. People with PN experience sensory discomfort, mainly in the extremities 
(numbness, dryness, tingling, burning, stinging, allodynia or hyperalgesia)3 which, over time, can 

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lead to the interruption of cancer treatment, with the risks that this entails. This condition often 
persists after the end of cancer treatment, which greatly affects the quality of life of those who 
suffer from it, as it can be uncomfortable when working, playing sports, carrying out household 
chores and even when socialising. In addition, the uncomfortable sensations can disturb sleep, 
which has an impact on mood. In general, people with NP caused by cancer treatments feel a 
great dissatisfaction with their skin. 
Currently, there is no effective treatment for NP, and when the symptomatology is severe and 
limits patients' daily life, some doctors recommend taking antidepressants, such as duloxetine, 
or discontinuing chemotherapy treatment4. Although a number of clinical trials aimed at finding 
an effective treatment for NP have been conducted in recent years, none of them have proven 
to be effective. Therefore, understanding the mechanisms governing the development of PN 
and its treatment is a huge challenge in oncology as it is one of the main causes of chemotherapy 
withdrawal.   
The Institute for Research, Development and Innovation in Health Biotechnology of the Miguel 
Hernández University of Elche (IDIBE-UMH) has been studying the mechanisms that govern skin 
imbalances for many years. This knowledge has been transferred to Prospera Biotech, and has 
been used to develop a line of creams for sensitive skin (trade name Nocisens). The mixture of 
fatty acids, tocopherol and innovative cosmetic ingredients means that Nocisens has a dual 
action on the stratum corneum. On the one hand, it strengthens the skin's barrier function by 
preventing water loss, which helps to increase hydration and re-establish the skin's protective 
function and, on the other hand, it prevents the accumulation of reactive oxygen species in the 
cells, protecting the skin from their harmful effects. These two actions help Nocisens cosmetic 
cream to create a feeling of well-being and comfort for the skin.  
However, in cosmetics, the degree of acceptance of a product is a key element for adherence to 
treatment. We have therefore developed two formulations derived from Nocicsens, PB-011 and 
PB-012, with slightly different texture, composition and properties in order to adapt them to the 
needs of the sensitive skin characteristic of palmo-plantar neuropathy mediated by 
chemotherapeutics.  
Given that PN induced by treatments with chemotherapy or chemotherapeutic agents fused to 
monoclonal antibodies (immunocytostatic) is characterised by skin imbalances that affect the 
quality of life of the people who suffer from it, a parallel, randomised, double-blind, masked 
study is proposed in patients who are about to begin oncological treatment to compare the 

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degree of acceptance of PB-011 and PB-012 cosmetic creams in this population. The study 
involves two populations: (i) the population where PB-011 cream will be tested; and, (ii) the 
population that will test PB-012 cream. The duration of the project will be 12 months, and 
participants will have to apply the cream once a day on their hands during the period of 
chemotherapy treatment. A sample size of 60 volunteers per population has been estimated to 
ensure statistical significance. As a relevant variable for the patients, the degree of skin 
satisfaction will be assessed every fortnight by means of a questionnaire only in the case of 
discomfort in the hands and/or feet.  
4. JUSTIFICATION AND STUDY OBJETCTIVES 
 
The toxicity generated during chemotherapy treatments can usually produce skin discomfort or 
peripheral polyneuropathy. CIPN manifests itself above all in the extremities, mainly in the 
palmar and plantar regions, giving rise to uncomfortable sensations such as itching, numbness, 
tingling, pain or dryness, i.e. skin sensitivity. Currently, there is no specific treatment to combat 
this skin sensitivity and oncology specialists recommend keeping the skin hydrated through the 
use of cosmetic creams. 
Taking into account that these sensations imply a deterioration in the quality of life of patients, 
our hypothesis is that cosmetic creams for sensitive skin with references PB011 and PB012 could 
improve comfort and the degree of satisfaction of cancer patients with CIPN. The reason for this 
hypothesis is that cosmetic creams contain ingredients that reinforce the barrier function of the 
epidermis and improve the hydration and appearance of the skin. The study has been designed 
to define which of the two creams produces greater satisfaction in patients. 
5. TYPE OF STUDY AND DESIGN 
5.1. Development phase 
Multicenter, controlled, parallel, randomized, double-blind, masked study.  
5.2. Randomization process 
The assignment of cosmetic creams PB-011 or PB-012 to patients will be carried out by a simple 
randomization procedure, using random numbers.  
5.3. Masking 

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To avoid bias, the study is proposed to be blind for patients and researchers and open to third 
parties (evaluators and those responsible for data analysis). To this end, a qualitative variable 
will be created, called product, of two degrees that will serve to mask the type of product used 
in each subject (PB-011/PB-012). The assignment of one product or another will be determined 
by the order of introduction in the study database. The definition of each degree of this 
qualitative variable will be in the possession of the main researcher and only when the study has 
finished and its results have been digitized, will it be transferred to those responsible for the 
statistical analysis. Both the data notebook and the databases or files used for statistical analysis 
will be dissociated from the identification data of the subjects under study. 
Doctores and other study collaborators will have access to a list containing a fixed order of the 
products (A/B). For instance: product 1 is A, product 2 is B, product 3 is B… Investigators will 
assign a cream A/B to participants as they enter in the study (participant 1 will have A, 2 will 
have B, 3 will have B, etc). This list will be available physically and electronically. 
6. SELECTION OF SUJECTS 
The inclusion of 120 patients who have been diagnosed with cancer in stages I-III and who are 
going to start chemotherapy treatment is proposed. Once the treatment is finished, the degree 
of cutaneous comfort will be compared between the patients who have developed peripheral 
neuropathy in both groups. 
6.1. Inclusion criteria 
Patients must meet all the criteria that appear in this section to be included in the study. 
• 
To be older tan 18 year old. 
• 
To be able to complete questionnaires. 
• 
Give informed consent in writing. 
• 
Being able to apply the product under test by oneself. 
• 
To have been diagnosed with stage I-III primary cancer. 
• 
To have received a maximum of one treatment session with chemotherapy (derivatives of 
taxane, platinum or vincristines). 
• 
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 
• 
Life expectancy greater than or equal to 6 months. 
6.2. Exclusion criteria  

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Patients who meet one or more of the following criteria will not be eligible to take part in the 
study despite meeting all the requirements of section 6.1: 
• 
Not being or having been treated with antidepressants, antiepileptics or HIV medication 
in the last 3 months. 
• 
Pre-existing peripheral neuropathies not related to chemotherapy treatment. 
• 
Pre-existing neurodegenerative or neuromuscular disease or history of stroke. 
• 
Family history of neuropathic diseases. 
• 
Having suffered in the last 6 months: myocardial infarction, unstable angina, stroke, 
transient ischemic attack, decompensated heart failure requiring hospitalization or class 
III/IV heart failure. 
• 
Being receiving investigational treatment (being involved in a clinical trial). 
• 
Evidence or indication of metastasis affecting the Central Nervous System. 
• 
Use of immunosuppressive or immunomodulatory medication that may lead to 
immunodeficiencies. 
• 
Not being treated with topical palmar and/or plantar medication. 
• 
Known hypersensitivity to capsaicin. 
• 
Having reduced capacity for expression or response to forms. 
• 
Not have been under general anesthesia for at least one month before starting the 
study. 
• 
Complication of peripheral polyneuropathy symptoms that require the use of specific 
medication. 
6.3. Expected number of subjects and justification 
A total of 120 volunteers diagnosed with any type of cancer, in stages I-III, who are about to start 
or have received a maximum of 1 dose of chemotherapy treatment will be studied. 
Two study populations are contemplated: (i) population that will receive the PB-011 cream; (ii) 
population that will receive the PB-012 cream. Both populations will apply the cream on their 
hands once a day. If sensory discomfort or, in the worst case, peripheral neuropathy appear 
during the chemotherapy treatment period, the application will be increased to twice daily on 
the affected areas (generally hands and feet). 
The number of volunteers for the study is 60 for each population. This value is based on: (i) a 
difference of 2 points between both populations (PB-011 and PB-012), on a satisfaction scale of 

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0 to 10 points, with 0 being very dissatisfied and 10 very satisfied, or 2 points on the Von Frey 
scale; (ii) a variability (standard deviation) of 3 points in each population; (iii) a p-value of 
statistical significance <0.05 and, (iv) a probability of finding a statistically significant difference 
for the p-value <0.05 of 95%. 
6.4. Duration of the recruitment period 
The recruitment period is estimated to last at 10 months. Patients should use the cream 
throughout the treatment period. 
7. PRODUCT DESCRIPTION 
 
7.1. Product 
Subjects who meet the inclusion/exclusion criteria and who become part of the study may take 
any medication that their physician deems appropriate, excluding those specified in the 
exclusion criteria. 
Patients participating in the study will apply: 
Cosmetic creams Ref. PB-011 and PB-012. 
Tradename: Nocisens.  
 
Business owner: Prospera Biotech S.L. 
 
Composition:  
● PB-011: Capric Triglyceride, Glyceryl Behenate, Glyceryl Stearate, Hydrogenated Castor 
Oil, Diethylene Glycol Monoethyl Ether, Tocopherol, Hydroxymethoxyiodobenzyl 
Glycolamide Perlargonate. 
● PB-012: Capric Triglyceride, Glyceryl Behenate, Glyceryl Stearate, Hydrogenated Castor 
Oil, Diethylene Glycol Monoethyl Ether, Tocopherol. 
7.2. Study development 
When a subject meets all the inclusion criteria and none of the exclusion criteria and has signed 
the informed consent document, he/she is electable to enter the study. The researchers will 
collect the data of each volunteer and notify Prospera Biotech of their inclusion. Patients will 

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receive the cream when they start the chemotherpaty treatment. Creams will be either sent 
directly to the participants’ home or sent in advance to the centers and stored there at room 
temperature (15-25ºC) until distributed to participants. The principal investigator will create the 
Data Notebook for each subject, anonymizing the personal and clinical data in all cases. The type 
of product to be assigned will be determined by the randomization procedure. 
Subjects taking part in the study should apply a sufficient amount of cream to their hands once 
a day for the duration of their chemotherapy treatment. Those subjects who develop skin 
sensitivity or peripheral neuropathy should undergo the following procedures:  
1. Increase the frecuency of use of the cream to twice a day in all affected areas. 
2. Once the chemotherapy treatment is finished: evaluation of the degree of skin 
satisfaction by means of a questionnaire that assesses the Dermatology Life Quality Index 
[DLQI] (Annex II) and the degree of satisfaction with the cream (Annex IV). Evaluation of 
the discomfort generated by peripheral neuropathy through a follow-up questionnaire 
(Annex III). Measurement of skin sensitivity using Von Frey hairs for patients who 
voluntarily wish to do so. These procedures will be carried out by the study collaborators 
of each center. In case of need, Prospera Biotech team could also contribute to make the 
follow-up (questionnaires) telematicallty. 
The study procedures are included in section 8.2. 
7.3. Withdrawal criteria 
Based on the provisions of the Declaration of Helsinki, the subjects have the right to withdraw 
from the study at any time and for any reason, being able to express it personally or through 
their representative. The investigator reserves the right to withdraw any subject from the study 
in the following cases: 
● Subject abandonment: violation of inclusion or exclusion criteria or non-cooperation. In 
case of withdrawal, the reason is reflected in the Data Notebook. 
● By efficacy criteria: if, in the investigator's opinion, the product is not causing any benefit 
to the subject under study. 
● Due to safety criteria: in the event of a serious or unexpected adverse event and that, 
for this reason, or due to the medication that may be instituted to reverse such event, 
it is considered that its continuation in the study is not pertinent.  

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8. STUDY DEVELOPMENT AND EVALUATION OF THE RESPONSE 
8.1. Study variables 
Main Variable: degree of skin satisfaction/comfort with the skin in the palmar and plantar 
regions, evaluated by means of the DLQI questionnaire. 
Secondary Variables:  
● Skin sensitivity quantifiable by the Von Frey filament test for patients who voluntarily so 
wish. 
● Follow-up of discomfort skin sensations experienced by patients, evaluated by means of 
a brief questionnaire. 
 
8.2. Collection of variables 
The main variable, degree of skin satisfaction/comfort, will be evaluated using the DLQI12, 13 
questionnaire available in ANNEX II. 
Mechanical sensitivity will be assessed by means of the Von Frey filament test in patients who 
voluntarily want to undergo it. The pain threshold and mechanical allodynia of patients with 
post-chemotherapy polyneuropathy will be measured before starting the study and once the 
chemotherapy treamtment is over, expressing the threshold in the minimum number of 
pressure units that trigger pain in patients with the corresponding filament. of Von Frey 
approved. 
The follow-up of the patients will be carried out through the usual oncological control during 
treatment. If the patients develop sensory or skin discomfort during this period, at the end of 
the treatment a check-up will be carried out using the following questionnaires: 
- 
 Follow-up of discomfort sensations available in a questionnaire derived from the 
Leonard Scale (ANNEX III). 
- 
Degree of skin satisfaction by means of the Dermatology Life Quality Index [DLQI] 
(Annex II). 
- 
Degree of satisfaction with the cream (Annex IV). 
 
 

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9. ADVERSE EVENTS  
An adverse event is considered to be any adverse medical event that occurs in a clinical research 
subject to whom a product has been administered, even if it does not necessarily have a causal 
relationship with this treatment. An adverse event can also be any unfavorable or unexpected 
sign, including an abnormal laboratory finding, symptom, or illness temporarily associated with 
the use of an investigational product, related or not. An adverse event is considered to be any 
adverse medical event that occurs in a clinical research subject to whom a product has been 
administered, even if it does not necessarily have a causal relationship with its use. An adverse 
event can also be any unfavorable or unexpected sign, including an abnormal laboratory finding, 
symptom, or illness temporarily associated with the use of an investigational product, related or 
not. 
Due to the fact the products in study are already commercialized, no adverse effects are 
expected. However, the recording of adverse events is an important aspect of study 
documentation, so the rules to follow are described below: 
9.1. Detection and documentation of adverse events 
Adverse events can be detected either by the subject himself or by the investigator, but it is the 
investigator's responsibility to record them. The Data Notebook will have a section for recording 
adverse events (Annex V) in which the investigator, or one of his collaborators, must describe 
events of this type in detail. The method of detecting adverse events can be either by direct 
communication from the subject under study, by exploration by the investigator, or by the 
subject's response to a question asked by the investigator or by any collaborator of the study. 
In any case, the existence of an adverse event must be duly documented and the nature of the 
event, the date of detection and the start date if they do not coincide, the duration, severity and 
possible relationship with the event must be recorded at each visit. product under study. 
The subjects in whom an adverse event is detected will be subjected to additional follow-up by 
the researchers, who will control the evolution of the adverse events until they have 
disappeared, decreased or stabilized. Follow-up information for these subjects should be 
brought to the attention of the study monitor. 
In addition to documenting the occurrence of any unexpected events, investigators should 
assess their intensity based on the following scale:  

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• 
Mild: adverse event that causes minimal discomfort, tolerable by the subject and 
that does not interfere with their daily activities. 
• 
Moderate: An adverse event bothersome enough to interfere with normal daily 
activities. 
• 
Severe: event or adverse reaction that requires hospitalization of the subject or 
prolongs it, that endangers his or her life, causes invalidity or permanent incapacity, 
gives rise to some anomaly or congenital malformation, or that produces his or her 
death). For notification purposes, those suspected adverse events or adverse 
reactions that are considered important from a medical point of view, even if they 
do not meet the above criteria, will also be treated as serious. 
Unexpected adverse reaction: adverse event whose nature or severity does not correspond to 
the information in the product's technical data sheet. 
9.2. . Assessment of causality 
The investigator should make every effort to explain each adverse event and assess its 
relationship, if any, to treatment with the study product. Causality should be assessed using the 
following categories: 
● Definitive: The adverse event follows a reasonable time sequence from the time of 
product administration and follows a known response pattern of the study product and 
cannot be reasonably explained by other factors such as the subject's clinical condition 
or other therapeutic interventions or concomitant medications administered to the 
subject and, in addition, one or more of the following: a) appears immediately after 
administration of the drug; b) improvement when discontinuing drug administration; c) 
reappears upon reintroduction of the drug. 
● Probable: The adverse event follows a reasonable time sequence from the time of 
product administration and follows a known response pattern to the study product and 
cannot be reasonably explained by other factors such as the subject's clinical condition 
or other therapeutic interventions or concomitant medications administered to the 
subject. 
● Possible: The adverse event follows a reasonable time sequence from the time of 
administration of the product and/or follows a known response pattern of the product 
under study, although it could be caused by other factors such as the clinical condition 

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of the subject or other therapeutic interventions or concomitant medications 
administered to the subject. 
● Unlikely: The adverse event is more likely to be caused by other factors such as the 
subject's clinical condition, therapeutic interventions, or concomitant medications 
administered to the subject and does not follow a known response pattern of the study 
product. 
● Unrelated: The adverse event is clearly related to other factors such as the subject's 
clinical status, therapeutic interventions, or concomitant medications administered to 
the subject. 
 
9.3. Procedures for immediate notification of serious or unexpected events 
A severe adverse event is considered to be any adverse medical event that at any dose: 
● Causes the death of the subject. 
● Puts life in danger. 
● Requires hospitalization of the subject or the extension of an existing hospitalization. 
● Causes significant or permanent disability/invalidity or a congenital abnormality/birth 
defect or overdose (accidental or deliberate).Produce la muerte del sujeto. 
The principal investigator will immediately notify the promoter of all serious adverse events. The 
initial communication will be followed by detailed written communications. In the initial and 
follow-up communications, the study subjects will be identified by means of a specific code 
number for each of them. In the event that a death of a subject participating in a trial has been 
reported, the investigator will provide the promoter and the Clinical Research Ethics Committees 
involved with all the additional information requested. 
The principal investigator will communicate serious and unexpected adverse events to the 
promoter by telephone, email or fax within 24 hours of the investigator becoming aware of the 
adverse event. The prior report made by telephone, email or fax must be followed by a complete 
report that includes a copy of the relevant data collected or recorded in the center or other 
documents produced as a result of the adverse event. 

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10. ETHICAL ASPECTS  
10.1. 
General Considerations  
This study must be carried out in accordance with the protocol and with the standards of good 
clinical practice, as described in: 
● Harmonized Tripartite Standards of the ICH E6, for Good Clinical Practice of 1996. 
● Regulation (EU) No 536/2014 of the European Parliament and of the Council, of April 16, 
2014. 
● ROYAL DECREE 1090/2015, of December 4, which regulates clinical trials with medicines, 
the Research Ethics Committees with medicines and the Spanish Registry of Clinical 
Studies. 
● Declaration of Helsinki and amendments regarding medical research in human beings. 
The researcher agrees, by signing this protocol, to follow the instructions and procedures 
described in it and therefore will comply with the principles of Good Clinical Practice on which 
it is based. Once the protocol is signed, it must not be modified without the written agreement 
of both the promoter and the principal investigator, and with the consent of the Research Ethics 
Committee. 
A signed and dated document confirming that the protocol, the informed consent form and the 
patient information sheets have been approved by the Ethics Commite must be delivered to the 
promoter, together with the name and position of the president and members of the Ethics 
Commite. 
10.2. 
Information to volunteers 
The investigator must explain to each subject the nature of the study, its purposes, procedures, 
expected duration and the potential risks and benefits related to participation in the study, as 
well as any inconvenience that this may entail. Each of the participants must be informed that 
tehir participation in the study is voluntary and that they can withdraw from the study at any 
time, without this affecting their subsequent medical treatment or their relationship with their 
treating physician. 
Informed consent will be provided in standard writing, in language easily understood by the 
participant. The subject must have sufficient time to read and understand the explanations 
before dating and signing the informed consent and must receive a copy of the signed 

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document. No subject can be included in the study without having previously given their 
informed consent. 
10.3. 
Confidentiality and Access to data 
The confidentiality of the personal data of the subjects will be maintained, although subject to 
the need, on the part of the monitor, to verify the original data against the clinical history of the 
subject. Only the date of birth and the study code will appear in the data collection notebook 
and in all study correspondence. The promoter will not keep any document with the name of 
any subject. At all times, the REGULATION of the European Union 2016/679 of April 27, 2016 
will be respected and complied with. Organic Law 3/2018, of December 5th, on the Protection of 
Personal Data and guarantee of digital rights. 
All information disclosed by the promoter to the researcher will be treated as strictly 
confidential. The investigator will only use this information for the study described in this 
protocol. It also undertakes not to disclose said information to third parties, except to other 
colleagues or employees who participate in the execution of the study and who are also bound 
by confidentiality obligations. 
*Depending on the nature of the contact data, it is possible that the email is identifying a patient (example: 
namesurname@.....com ). In these cases, if patients do not wish to transfer data that may be identifying, 
an anonymized email can be created (Patient code@prosperabiotech.com ) or they can choose to follow 
up by telephone contact. 
10.4. 
Econocmic report 
Given that there is no deviation from the conditions of use established in the product 
instructions, the center promoting the study (PROSPERA BIOTECH) will provide both creams to 
the subjects. 
The detailed relation of the costs of this study is contemplated in ANNEX XI. 
10.5. 
Insurance police 
An insurance policy has been contracted with Berkley company with address at Paseo de la 
Castellana 141, Planta 18, 28046 Madrid. This insurance covers personal damage caused to the 
subjects as a result of the study, as well as economic damage arising directly from the same, in 
accordance with Royal Decree 1090/2015, of December 4. In addition to the legal civil liability 
of the study promoter, the legal civil liability of the researcher and his collaborators, that of the 

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hospital or center where the study is carried out, as well as that of the owner of the study, is 
covered. 
11. PRACTICAL CONSIDERATIONS 
11.1. 
Responsibilities of all study participants 
Investigator: The investigators will abide by the Good Clinical Practice standards and will know 
and follow the Standard Operating Procedures (SOPs) of the relevant Clinical Trials Unit. All the 
information collected during the execution of the project will be recorded directly in the data 
collection notebook, which is attached as Annex I. When a correction is made, the date and the 
initials of the person who makes it must be noted. 
Auxiliary Personnel: The auxiliary personnel will follow the instructions given by the investigator. 
Monitor. The montor must attest that the information compiled in the protocol is true, for which 
you must have all kinds of facilities from the research team to carry out their work. 
Promoter: will be responsible for ensuring compliance with the relevant legal regulations and 
for supplying the product under study. 
11.2. 
Protocol deviations 
When a situation that causes a deviation from the protocol occurs, the deviation will be only for 
that subject. Investigators present in such circumstances will fully document the deviation and 
reason on the Data Notebook. In the event that the deviation has to do with the 
inclusion/exclusion criteria, the investigators will contact the clinical monitor by telephone in 
order to inform them of such deviation. 
11.3. 
Collection and filing of documentation  
There will be a documentation file for all the data, which will be kept for 5 years after the end 
of the study. This file must contain the following elements:  
● Approval by the Ethical Committe of the protocol and the informed consent form. 
● Copy of the written consent form and the approved protocol with any amendments if 
applicable. 
● Any correspondence related to the study with the promoter, during the course of the 
study. 

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● Any correspondence with the Ethics Committe. 
● Signed acceptance of the protocol. 
● Curriculum vitae of the principal investigator and of the other investigators who make 
up the research team. 
● Register of signatures of the members of the research team. 
● Communications of serious adverse events. 
● Contract between the promoter and the hospital when applicable 
● Copies of Data Notebook. 
 
11.4. 
Amendents to the protocol 
Neither the investigator, nor the monitor, nor the promoter will modify this protocol without 
first obtaining the consent of the other parties. The modification must be documented in 
writing. Any change in the research activity, except those necessary to eliminate an immediate 
apparent risk to the volunteer, must be reviewed and approved by the Ethics Committe before 
implementation. The promoter must send the amendments to the protocol to the health 
authorities, and the modifications may require the review and approval of the Ethics Committe. 
11.5. 
Investigator Acceptance  
The researcher commitment is included, if needed, in the documentation submitted to the 
Ethics Committe.  
12. STATISTICAL ANALYSES  
The analysis of the results of this study will be approached from two perspectives. On the one 
hand, the modified intention-to-treat (MITT) population will be analyzed, which corresponds to 
all those subjects who have used the product at least once and for whom satisfaction data is 
available. On the other hand, a per-protocol analysis will be carried out in which all randomized 
subjects who have followed the study instructions until the end of the study will be included. 
The clinical evaluation data may be analyzed as quantitative or qualitative variables. In the first 
case, the results will be expressed as mean ± standard deviation, minimum and maximum. In 
the case of qualitative variables, the results will be expressed as frequency and percentage. For 
all the parameters to be measured (both clinical variables and responses to questionnaires) 
there will be a baseline measurement taken before the start of the protocol that will serve as a 
control measurement. The change in the main variable (degree of satisfaction) will be analyzed 

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using the paired Student's T test. The change in the secondary variables will be studied according 
to their nature (qualitative or quantitative variables) and applying the corresponding test in each 
case: Chi square, Student's T, ANOVA, Kruskal-Wallis or Mann-Whitney U. The impact of each 
variable on the main variable will be assess, especially the impact of treatment, diagnosis, age 
and gender. 
13. REFERENCES 
1. Roy PS, Saikia BJ. Cancer and cure: A critical analysis. Indian J Cancer. 2016;53(3):441-2. 
2. Zajączkowska R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms 
of Chemotherapy-Induced Peripheral Neuropathy. Int J Mol Sci. 2019 Mar 22;20(6). 
3. Brzeziński K. Chemotherapy-induced polyneuropathy. Part I. Pathophysiology. Contemp 
Oncol (Pozn). 2012;16(1):72-8. 
4. Areti A, Yerra VG, Naidu V, Kumar A. Oxidative stress and nerve damage: role in 
chemotherapy induced peripheral neuropathy. Redox Biol. 2014 Jan 18;2:289-95. 
 
 

Reference 20PB-02 
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ANNEX I: DATA NOTEBOOK 
See attached document 
 
 

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26 
 
ANNEX II: DERMATOLOGY LIFE QUALITY INDEX  
See attached document 
 
 

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ANNEX III: QUESTIONNAIRE FOR THE MONITORING OF DISCOMFORT DUE 
TO PERIPHERAL POLYNEUROPATHY 
See attached document 
 
 

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28 
 
ANNEX IV: SATISFACTION QUESTIONNAIRE 
Tittle: Study for the evaluation of the degree of skin satisfaction of cosmetic creams PB-011 and 
PB-012 for sensitive skin in oncological patients affected by a palmoplantar polyneuropathy 
secondary to taxanes.   
Principal Investgator:  Jesús Mauel Poveda Ferriols 
Reference: 20PB-02 
1. Has applying the cream to your hands and/or feet caused you any discomfort? 
Nothin  
 
 
 
 
 
 
 
Many 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
2. Has the application of the cream to your hands and/or feet generated any kind of skin 
reaction? 
 
Nothin  
 
 
 
 
 
 
 
Many 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
3. How would you define your degree of satisfaction with the cream? 
 
Nada 
 
 
 
 
 
 
 
 
Mucho 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
If, sensorial discomfort or CIPN have appeared during the chemotherapy treatment please 
answer also:  
 
1. When you apply the cream to your hands and/or feet, do you feel any relief from any of 
the sensations that bother you? 
YES 
NO 
 
2.  Has the application of the cream generated comfort in your skin sensitivity on the hands 

Reference 20PB-02 
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29 
 
and/or feet? 
 
Nothing  
 
 
 
 
 
 
 
A lot 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 

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ANNEX V: NOTIFICATION OF POSSIBLE ADVERSE REACTIONS 
Subject identification: 
Protocol 
20PB-02 
Nº notification 
 
Subject identification number 
 
Report type 
Initial         Follow-up 
Reaction Characteristics: 
Study inclusion date: 
Adverse Event Description: 
Date of first application: 
Date 
of 
adverse 
reaction 
appearance: 
 
 
Severity Adverse Reaction 
Mild             Moderate             Severe 
Consequence Adverse Reaction 
 
Information on the product under study: 
Suspicious Product 
Doe 
Route 
Starting date: 
 
 
 
End date: 
Did the adverse effect subside when suspending the application 
of the product? 
Did the effect reappear when 
applying the product again? 
YES       NO           NOT APPLICABLE 
  
YES       NO 
NOT APPLICABLE 
Information to take into account and medical history: 

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Concomitant Medication 
Reason of Prescription Had the patient experienced or recorded 
the side effect before? 
  
 
YES         NO 
 
 
When? 
 
 
 
What was it related to? 
 
 
Other relevant data from the clinical history: 
 
Investigator Name: 
Position: 
Is additional documentation attached? YES        NO 
Which? 
 

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ANNEX VI: DECLARATION OF HELSINKI 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 
and amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
 
Preamble 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement of ethical principles for medical research involving human subjects, including 
research on identifiable human material and data. 
 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should 
be applied with consideration of all other relevant paragraphs. 
 
2.Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. 
The WMA encourages others who are involved in medical research involving human subjects to 
adopt these principles. 
 
General Principles 
3.The Declaration of Geneva of the WMA binds the physician with the words, “The health of my 
patient will be my first consideration,” and the International Code of Medical Ethics declares 
that, “A physician shall act in the patient’s best interest when providing medical care.” 
 
4. It is the duty of the physician to promote and safeguard the health, well-being and rights of 
patients, including those who are involved in medical research. The physician’s knowledge and 
conscience are dedicated to the fulfilment of this duty. 
 

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5. Medical progress is based on research that ultimately must include studies involving human 
subjects. 
 
6. The primary purpose of medical research involving human subjects is to understand the 
causes, development and effects of diseases and improve preventive, diagnostic and 
therapeutic interventions (methods, procedures and treatments). Even the best proven 
interventions must be evaluated continually through research for their safety, effectiveness, 
efficiency, accessibility and quality. 
 
7. Medical research is subject to ethical standards that promote and ensure respect for all 
human subjects and protect their health and rights. 
 
8. While the primary purpose of medical research is to generate new knowledge, this goal can 
never take precedence over the rights and interests of individual research subjects. 
 
9. It is the duty of physicians who are involved in medical research to protect the life, health, 
dignity, integrity, right to self-determination, privacy, and confidentiality of personal 
information of research subjects. The responsibility for the protection of research subjects must 
always rest with the physician or other health care professionals and never with the research 
subjects, even though they have given consent. 
 
10. Physicians must consider the ethical, legal and regulatory norms and standards for research 
involving human subjects in their own countries as well as applicable international norms and 
standards. No national or international ethical, legal or regulatory requirement should reduce 
or eliminate any of the protections for research subjects set forth in this Declaration. 
 
11. Medical research should be conducted in a manner that minimises possible harm to the 
environment. 
 
12. Medical research involving human subjects must be conducted only by individuals with the 
appropriate ethics and scientific education, training and qualifications. Research on patients or 
healthy volunteers requires the supervision of a competent and appropriately qualified 
physician or other health care professional. 
 

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13. Groups that are underrepresented in medical research should be provided appropriate 
access to participation in research. 
 
14. Physicians who combine medical research with medical care should involve their patients in 
research only to the extent that this is justified by its potential preventive, diagnostic or 
therapeutic value and if the physician has good reason to believe that participation in the 
research study will not adversely affect the health of the patients who serve as research 
subjects. 
 
15. Appropriate compensation and treatment for subjects who are harmed as a result of 
participating in research must be ensured. 
 
Risks, Burdens and Benefits 
16. In medical practice and in medical research, most interventions involve risks and burdens. 
 
Medical research involving human subjects may only be conducted if the importance of the 
objective outweighs the risks and burdens to the research subjects. 
 
17. All medical research involving human subjects must be preceded by careful assessment of 
predictable risks and burdens to the individuals and groups involved in the research in 
comparison with foreseeable benefits to them and to other individuals or groups affected by the 
condition under investigation. 
 
Measures to minimise the risks must be implemented. The risks must be continuously 
monitored, assessed and documented by the researcher. 
 
18. Physicians may not be involved in a research study involving human subjects unless they are 
confident that the risks have been adequately assessed and can be satisfactorily managed. 
 
When the risks are found to outweigh the potential benefits or when there is conclusive proof 
of definitive outcomes, physicians must assess whether to continue, modify or immediately stop 
the study. 
 
Vulnerable Groups and Individuals 

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19. Some groups and individuals are particularly vulnerable and may have an increased 
likelihood of being wronged or of incurring additional harm. 
 
All vulnerable groups and individuals should receive specifically considered protection. 
 
20.  Medical research with a vulnerable group is only justified if the research is responsive to the 
health needs or priorities of this group and the research cannot be carried out in a non-
vulnerable group. In addition, this group should stand to benefit from the knowledge, practices 
or interventions that result from the research. 
 
Scientific Requirements and Research Protocols 
21. Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant sources 
of information, and adequate laboratory and, as appropriate, animal experimentation. The 
welfare of animals used for research must be respected. 
 
22. The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol. 
 
The protocol should contain a statement of the ethical considerations involved and should 
indicate how the principles in this Declaration have been addressed. The protocol should include 
information regarding funding, promoters, institutional affiliations, potential conflicts of 
interest, incentives for subjects and information regarding provisions for treating and/or 
compensating subjects who are harmed as a consequence of participation in the research study. 
 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial 
provisions. 
 
Research Ethics Committees 
23. The research protocol must be submitted for consideration, comment, guidance and 
approval to the concerned research ethics committee before the study begins. This committee 
must be transparent in its functioning, must be independent of the researcher, the promoter 
and any other undue influence and must be duly qualified. It must take into consideration the 
laws and regulations of the country or countries in which the research is to be performed as well 

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as applicable international norms and standards but these must not be allowed to reduce or 
eliminate any of the protections for research subjects set forth in this Declaration. 
 
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse 
events. No amendment to the protocol may be made without consideration and approval by the 
committee. After the end of the study, the researchers must submit a final report to the 
committee containing a summary of the study’s findings and conclusions. 
 
Privacy and Confidentiality 
24. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information. 
 
Informed Consent 
25. Participation by individuals capable of giving informed consent as subjects in medical 
research must be voluntary. Although it may be appropriate to consult family members or 
community leaders, no individual capable of giving informed consent may be enrolled in a 
research study unless he or she freely agrees. 
 
26. In medical research involving human subjects capable of giving informed consent, each 
potential subject must be adequately informed of the aims, methods, sources of funding, any 
possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits 
and potential risks of the study and the discomfort it may entail, post-study provisions and any 
other relevant aspects of the study. The potential subject must be informed of the right to refuse 
to participate in the study or to withdraw consent to participate at any time without reprisal. 
Special attention should be given to the specific information needs of individual potential 
subjects as well as to the methods used to deliver the information. 
 
After ensuring that the potential subject has understood the information, the physician or 
another appropriately qualified individual must then seek the potential subject’s freely-given 
informed consent, preferably in writing. If the consent cannot be expressed in writing, the non-
written consent must be formally documented and witnessed. 
 
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study. 

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27. When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or 
may consent under duress. In such situations the informed consent must be sought by an 
appropriately qualified individual who is completely independent of this relationship. 
 
28. For a potential research subject who is incapable of giving informed consent, the physician 
must seek informed consent from the legally authorised representative. These individuals must 
not be included in a research study that has no likelihood of benefit for them unless it is intended 
to promote the health of the group represented by the potential subject, the research cannot 
instead be performed with persons capable of providing informed consent, and the research 
entails only minimal risk and minimal burden. 
 
29. When a potential research subject who is deemed incapable of giving informed consent is 
able to give assent to decisions about participation in research, the physician must seek that 
assent in addition to the consent of the legally authorised representative. The potential subject’s 
dissent should be respected. 
 
30. Research involving subjects who are physically or mentally incapable of giving consent, for 
example, unconscious patients, may be done only if the physical or mental condition that 
prevents giving informed consent is a necessary characteristic of the research  group. In such 
circumstances the physician must seek informed consent from the legally authorised 
representative. If no such representative is available and if the research cannot be delayed, the 
study may proceed without informed consent provided that the specific reasons for involving 
subjects with a condition that renders them unable to give informed consent have been stated 
in the research protocol and the study has been approved by a research ethics committee. 
Consent to remain in the research must be obtained as soon as possible from the subject or a 
legally authorised representative. 
 
31. The physician must fully inform the patient which aspects of their care are related to the 
research. The refusal of a patient to participate in a study or the patient’s decision to withdraw 
from the study must never adversely affect the patient-physician relationship. 
 
32. For medical research using identifiable human material or data, such as research on material 
or data contained in biobanks or similar repositories, physicians must seek informed consent for 

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its collection, storage and/or reuse. There may be exceptional situations where consent would 
be impossible or impracticable to obtain for such research. In such situations the research may 
be done only after consideration and approval of a research ethics committee. 
 
Use of Placebo 
33. The benefits, risks, burdens and effectiveness of a new intervention must be tested against 
those of the best proven intervention(s), except in the following circumstances: 
 
Where no proven intervention exists, the use of placebo, or no intervention, is acceptable; or 
 
Where for compelling and scientifically sound methodological reasons the use of any 
intervention less effective than the best proven one, the use of placebo, or no intervention is 
necessary to determine the efficacy or safety of an intervention 
 
and the patients who receive any intervention less effective than the best proven one, placebo, 
or no intervention will not be subject to additional risks of serious or irreversible harm as a result 
of not receiving the best proven intervention. 
 
Extreme care must be taken to avoid abuse of this option. 
 
Post-Trial Provisions 
34. In advance of a clinical trial, promoters, researchers and host country governments should 
make provisions for post-trial access for all participants who still need an intervention identified 
as beneficial in the trial. This information must also be disclosed to participants during the 
informed consent process. 
 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human subjects must be registered in a publicly accessible 
database before recruitment of the first subject. 
 
36. Researchers, authors, promoters, editors and publishers all have ethical obligations with 
regard to the publication and dissemination of the results of research. Researchers have a duty 
to make publicly available the results of their research on human subjects and are accountable 
for the completeness and accuracy of their reports. All parties should adhere to accepted 
guidelines for ethical reporting. Negative and inconclusive as well as positive results must be 

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published or otherwise made publicly available. Sources of funding, institutional affiliations and 
conflicts of interest must be declared in the publication. Reports of research not in accordance 
with the principles of this Declaration should not be accepted for publication. 
 
Unproven Interventions in Clinical Practice 
37.  In the treatment of an individual patient, where proven interventions do not exist or other 
known interventions have been ineffective, the physician, after seeking expert advice, with 
informed consent from the patient or a legally authorised representative, may use an unproven 
intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or 
alleviating suffering. This intervention should subsequently be made the object of research, 
designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, 
where appropriate, made publicly available. 
 
 

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ANNEX VII: PATIENT INFORMATION SHEET 
Through this document you can find out about the study in which you are being offered to 
participate. Take the time you need to read it carefully and ask your doctor any questions you 
may have. 
Objective 
To evaluate and compare the degree of skin satisfaction and comfort of cancer patients with 
cosmetic creams for sensitive skin PB011 and PB-012 after having developed sensitivity as a 
result of chemotherapy treatment. 
Procedure description 
If you agree to participate in this study, you will need to apply a cosmetic hand cream once a 
day during the course of your chemotherapy treatment. If at any time you decide to withdraw 
from the study and stop applying the product, notify your oncologist. 
If, during treatment, you develop sensitivity or sensory discomfort, you can increase the dose of 
cream to twice a day. At the end of cancer treatment, you will be asked for your opinion through 
two short questionnaires. In addition, your doctor may request the analytical or radiological 
tests that he considers appropriate to control your health status and to diagnose any change in 
it that may occur due to the progress of your disease. 
All the procedures of this study have been approved by an Ethics Committee and are governed 
by the principles contained in the Declaration of Helsinki. 
Beneffits 
The daily application of the product under study is expected to produce an increase in the degree 
of skin satisfaction and comfort in people undergoing chemotherapy derived sensitivity. This will 
result in an improvement in your quality of life. You must take into account that the action of 
the product is not immediate. The efficacy of the test cream is based on a slow process of 
reinforcing the skin's natural protection barrier. Therefore, the beneficial effects of the product 
will begin to be observed between 4-8 weeks of continuous application. Bearing this in mind, 
we strongly urge you not to desist from applying the product if you notice an improvement in 
your skin discomfort, as this could lead to a reactivation of the discomfort. 
Risks 

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The products under study are two creams derived from the NOCISENS cosmetic line (marketed 
for the treatment of sensitive skin). They have passed all the relevant quality and safety controls 
in volunteers, being certified as dermatologically safe products, presenting no adverse skin 
effects. In addition, they do not present any contraindication. Therefore, the topical application 
of these products does not pose a risk to your health. However, if during the course of the study 
you suffer any type of adverse skin reaction, you should notify your doctor as soon as possible 
and follow his instructions. Any new information about the product that may appear during the 
course of the study will be communicated to you as soon as possible. 
 
Conditions of participation 
Your participation in this study is completely voluntary. If you decide to participate, you are free 
to withdraw from it when you deem it appropriate without having to give any explanation and 
without this decision entailing any type of penalty, or changes in your treatment or relationship 
with the doctors who treat you. Participation or non-participation in this study will not affect 
your medical care. 
This study aims to answer relevant questions to, in the future, improve the quality of life of 
people like you. The costs of the study and the insurance policies are financed by PROSPERA 
BIOTECH S.L. 
The promoter of the study has an insurance policy that conforms to current legislation (Royal 
Decree 1090/2015, of December 4) and whose purpose is to provide any compensation and 
indemnity in the event of damage to your health or injuries that may occur in connection with 
your participation in the study. 
Confidentiality 
During the course of the study, it is possible that the doctors and researchers participating in it 
have access to clinical data about your history, your illness and your current situation, as well as 
the information that you provide in consultations. We are aware of the sensitive nature of said 
information and, therefore, we undertake to keep it confidentially at all times. Your name or any 
data that can identify you will be excluded from the study databases, being replaced by a code. 
Only the doctor who treats you in consultation and the promoter of the research project may 
have access to the correspondence between your personal data and the identification code. At 
all times, the current regulations on the processing of personal data regulated by the 
REGULATION of the European Union 2016/679 of April 27, 2016 will be respected.  

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Due to the exceptional situation of the COVID-19 pandemic experienced in 2020, the monitoring 
of the study will be carried out electronically through a web application or telephone contact. 
To do this, you must provide your contact information (email and/or telephone). In the event 
that your email address is identifying (example: namesurname@....com) and you do not wish to 
provide 
it, 
you 
may 
be 
provided 
with 
an 
anonymized 
address 
(studycode@prosperabiotech.com). 
The results of the study may be published in the media, magazines, and scientific conferences; 
assigned to public or private research centers; or become part of the material intended for 
teaching or research. However, your personal data will always be excluded from the information 
that is transferred. 
 
You may, at any time, exercise your rights of access, rectification, cancellation and opposition, 
communicating it in writing or sending an e-mail to info@prosperabiotech.com or 
mgarcia@prosperabiotech.com 
 
 
 

Reference 20PB-02 
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Contact data:  
 
St. Pierre Hospital 
Project promoter: PROSPERA BIOTECH 
Dr. Jesús Manuel Poveda Ferriols 
jesus.poveda@stpierre-bru.be 
Dra. Marta García Escolano 
E-mail: mgarcia@prosperabiotech.com  
Tel: 663779125 
 
 
 

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ANNEX VIII: INFORMED CONSENT FORM FOR THE PATIENT 
Tittle: Study for the evaluation of the degree of skin satisfaction of cosmetic creams PB-011 and 
PB-012 for sensitive skin in oncological patients affected by a palmoplantar polyneuropathy 
secondary to taxanes.   
Principal Investgator:  Jesús Mauel Poveda Ferriols 
Reference: 20PB-02 
 
I, _____________________________________________________, with ID nº_____________, 
                                                      (name and surname)                                                                                                  (ID) 
● I have read the information sheet and have had sufficient time to consider my decision. 
● I have been able to ask questions and all of them have been answered satisfactorily. 
● I have received sufficient information about the study and understand that my 
participation in the study is voluntary. 
● I have spoken with _______________________________________________________. 
                                                                           (Investigator name and surname) 
 
I understand that I can withdraw from the study: 
• 
Whenever I want. 
• 
Without having to explain. 
• 
Without this affecting my medical care. 
I freely give my consent to participate in the study and, therefore, I give my consent for the 
access and use of my data under the conditions detailed in the information sheet. 
And therefore I sign: 
In_____________ on _________   ___, 20___ 
 (place)                                                                   (date) 
 
 
 
 
 

Reference 20PB-02 
Date: July 2022  
45 
 
Patient signature 
Investigator Signature 
Date: 
Date: 
 
 

Reference 20PB-02 
Date: July 2022  
46 
 
ANNEX IX: INFORMED CONSENT REVOCATION SHEET 
Tittle: Study for the evaluation of the degree of skin satisfaction of cosmetic creams PB-011 and 
PB-012 for sensitive skin in oncological patients affected by a palmoplantar polyneuropathy 
secondary to taxanes.   
Principal Investgator:  Jesús Mauel Poveda Ferriols 
Reference: 20PB-02 
 
I, __________________________________________________, with ID nº_______________, 
revoke the consent given on the date _______________ and I do not wish to continue 
participating in the study entitled: “Study for the evaluation of the degree of skin satisfaction of 
cosmetic creams PB-011 and PB-012 for sensitive skin in oncological patients affected by a 
palmoplantar polyneuropathy secondary to taxanes”.   
 
And therefore I sign: 
In_____________ on _________   ___, 20___ 
 (place)                                                                   (date) 
 
 
 
 
 
 
Patient signature 
Investigator Signature 
Date: 
Date: 
 
 
 
 
 

Reference 20PB-02 
Date: July 2022  
47 
 
ANNEX X: ECONOMIC REPORT 
See attached document