Evaluation of the Performance and Safety of a Type I Collagen-Based Medical Device (MD-Small Joints Collagen Medical Device) i the Treatment of RHIZOARTROSIS. "SMAGENART PILOT STUDY"
Phase: NA
Conditions: Trapeziometacarpal Osteoarthritis, Rhizarthrosis, MEDICAL DEVICE, Infiltrate
Sponsor: Guna S.p.a

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CLINICAL INVESTIGATION PLAN (CIP) 
FOR A MEDICAL DEVICE 
“SMAGENART” 
TITLE: EVALUATION OF THE PERFORMANCE AND SAFETY OF A TYPE I COLLAGEN-BASED MEDICAL 
DEVICE (MD-SMALL JOINTS COLLAGEN MEDICAL DEVICE) IN THE TREATMENT OF 
RHIZOARTHROSIS. "SMAGENART PILOT STUDY". 
 
 
IDENTIFICATION CODE: 
MDG20232202 
EUDRACT: 
NA 
CLINICAL INVESTIGATION PLAN VERSION  
AND DATE: 
 
n° 3.0 in 21 September 2023 
ACTORS:  
 
 
Dr. Federico Giarda, Dr. Vincenzo Miranda. 
SIGNATURE OF SCIENTIFIC COORDINATOR: Dr. Federico Giarda 
 
_________________________________________________ 
DATE: 
21-09-2023 
NUMBER OF PAGE 
n° 33 
 
 
This document contains confidential information belonging to GUNA S.p.A. Milan, Italy. 
The information contained in this document may not be disclosed or used by third parties without the written permission of 
GUNA S.p.A. 
The only exceptions to these restrictions are the Investigators participating in this Clinical Investigation. 
 

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GENERAL INFORMATIONS 
 
Scientific Coordinator 
Dr. Federico Giarda 
Specialista in Medicina Fisica e Riabilitativa 
S.C. di Medicina Riabilitativa e 
Neuroriabilitazione 
ASST Grande Ospedale Metropolitano Niguarda 
Piazza dell'Ospedale Maggiore, 3  
20162 Milano, Italia 
 
Sponsor 
Guna S.p.a. 
Via Palmanova, 71 
20132 Milano, Italia 
Tel: +39 02280181 
e-mail: clinical@guna.it 
 
Study ID Name 
“SMAGENART PILOT STUDY” 
 
Study Type 
One sample bicentric pilot Clinical Investigation 
 
Condition 
Rizarthrosis 
Intervention 
MD-Small Joints 
Guna Collagen Medical Device 
Phase 
IV Post 
Market 
 
Operative Units 
ASST Grande Ospedale Metropolitano 
Niguarda 
S.C. di Medicina Riabilitativa e 
Neuroriabilitazione e  
Dipartimento Neuroscienze Testa Collo 
Piazza dell'Ospedale Maggiore, 3  
20162 Milano, Italia 
 
Istituto 
Neurologico Mediterraneo I.R.C.C.S Neuromed  
U.O.S.D. Medicina del Dolore 
Via Atinense, 18  
86077 Pozzilli (IS), Italia 
 
Principal investigators 
Dr. Federico Giarda 
S.C. di Medicina Riabilitativa e 
Neuroriabilitazione 
ASST Grande Ospedale Metropolitano Niguarda 
Tel: +39 0264442414 
e-mail: federico.giarda@ospedaleniguarda.it 
 

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Dr. Massimo Luzi 
Direttore U.O.S.D. Medicina del Dolore 
Istituto 
Neurologico Mediterraneo I.R.C.C.S Neuromed  
e-mail: massimoluzi@libero.it 
 
Co-investigators 
Dr.ssa Luciana Sciume 
S.C. di Medicina Riabilitativa e 
Neuroriabilitazione 
ASST Grande Ospedale Metropolitano Niguarda 
Tel: +39 0264442414 
e-mail: luciana.sciume@ospedaleniguarda.it 
 
Dr. Bruno De Meo 
Responsabile Ambulatorio 
U.O.S.D. Medicina del Dolore 
Istituto 
Neurologico Mediterraneo I.R.C.C.S Neuromed  
Tel: +39 3293974245 
e-mail: bruno.demeo@yahoo.it 
 
Sponsor’s Clinical Research Manager 
Dr. Vincenzo Miranda 
Clinical Research Unit 
Via Palmanova, 71 
20132 Milano, Italia 
Tel: +39 0228018358 
e-mail: v.miranda@guna.it 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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DECLARATION OF CONFORMITY 
 
I agree to conduct this Clinical Investigation in accordance with all the requirements of the 
Investigation Plan, according to the Good Clinical Practice (ICH/GCP) guidelines, the principles set 
forth in the Declaration of Helsinki (Fortaleza 64th, 2013), and the applicable regulations [Regulation 
(EU) 2017/745]. 
 
Principal Investigator 
Name and Surname: 
Federico dr. Giarda 
Title: 
Specialist in Physical and Rehabilitation Medicine 
Institution: 
ASST Grande Ospedale Metropolitano Niguarda, Milano 
 
Date…………………………………………………Signature………………………………………………………………………………… 
 
Co-Investigator 
Name and Surname: 
Luciana dr.ssa Sciumé 
Title: 
Specialist in Physical and Rehabilitation Medicine 
Institution: 
ASST Grande Ospedale Metropolitano Niguarda, Milano 
 
Date…………………………………………………Signature………………………………………………………………………………… 
 
Principal Investigator 
Name and Surname: 
Massimo dr. Luzi 
Title: 
Specialist in Anesthesia and Resuscitation 
Institution: 
Istituto Neurologico Mediterraneo I.R.C.C.S Neuromed 
 
Pozzilli (IS) 
 
Date…………………………………………………Signature……………………………………………………………………………… 
 
Co-Investigator 
Name and Surname: 
Bruno dr. De Meo 
Title: 
Specialist in Anesthesia and Resuscitation 
Institution: 
Istituto Neurologico Mediterraneo I.R.C.C.S Neuromed 
 
Pozzilli (IS) 
 
Date……………………………………………Signature……………………………………………………………………………………. 

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KEY ROLES 
 
Scientific Coordinator and Principal Investigator 
Name and Surname: 
Federico dr. Giarda 
Title: 
Specialist in Physical and Rehabilitation Medicine  
Institution: 
ASST Grande Ospedale Metropolitano Niguarda, Milano 
Tel:  
+39 0264442414 
e-Mail: 
federico.giarda@ospedaleniguarda.it 
 
Date………………………………………………Signature………………………………………………………………………………… 
 
 
Clinical Research Manager Guna S.p.a. 
Name and Surname 
Vincenzo dr. Miranda 
Title: 
Dr in Pharmacist (PharmD) 
Institution: 
Guna S.p.a. Milano, Italia 
Tel:  
+39 0228018358/+39 3351311917 
e-Mail: 
 
vincenzo.miranda@guna.it 
 
Date…………………………………………………Signature………………………………………………………………………………… 
 
 
Pharmacovigilance Manager Guna S.p.a. 
Name and Surname: 
Marco dr. Rossi 
Title: 
Doctor in Chemistry and Pharmaceutical Technologies 
Institution: 
Guna S.p.a. Milano, Italia 
Tel:  
 
+39 0228018458 
e-Mail: 
 
marco.rossi@guna.it 
 
Date…………………………………………………Signature……………………………………………………………………………… 
 
 
Quality Unit Director GUNA S.p.a. 
Name and Surname: 
 
Dr.ssa Patrizia Rossi 
Title:  
 
Doctor in Chemistry and Pharmaceutical Technologies 

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Institution: 
Guna S.p.a. Milano, Italia 
Tel:  
 
+39 0228018418 
e-Mail: 
 
patrizia.rossi@guna.it 
 
Date…………………………………………………Signature……………………………………………………………………………… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
1. 
SYNOPSIS 
2. 
LIST OF ABBREVIATIONS 
3. 
INTRODUCTION 
3.1 
Functional Anatomy of the Trapeziometacarpal Joint 
3.2 
Osteoarthritis of the Trapeziometacarpal Joint 
3.3 
Rationale for the Clinical Investigation 
4. 
SCIENTIFIC REQUIREMENTS 
4.1 
Research Title 
4.2 
Research Objective 
4.3 
Investigation Design 
4.4 
Investigation Duration 
4.5 
Participating Population 
4.6 
Enrollment 
4.7 
Selection Criteria 
4.7.1 
Inclusion Criteria 
4.7.2 
Exclusion Criteria 
4.8 
Subject Coding 
4.9 
Procedures rocedure 
4.9.1 
Evaluation Timepoints 
4.9.2 
Visit Schedule 
4.10 
Materials Required for Conducting the Investigation 
4.11 
Study Group 
4.12 
Infiltration Technique 
4.13 
Efficacy Criteria 
4.14 
Primary Endpoint 
4.15 
Secondary Endpoints 
4.16 
Data Collection 
4.17 
Early Termination of the Investigation 
5. 
STATISTICS 
5.1 
Sample Size 
5.2 
Statistical Analysis Plan 
5.2.1 
Descriptive Statistics 
5.2.2 
Primary Endpoint 

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5.2.3 
Secondary Endpoints 
6. 
ETHICAL REQUIREMENTS 
6.1 
Ethical Authorizations 
6.2 
Amendments to the Investigation Plan 
6.3 
Subject Information 
6.4 
Adverse Events 
6.5 
Privacy Protection 
6.6 
Data Access 
6.7 
Data Ownership 
6.8 
Data Processing and Publication 
6.9 
Funding 
6.10 
Ethical Code of Reference 
6.11 
Subject Insurance 
7. 
PREMATURE INTERRUPTION OF THE INVESTIGATION 
8. 
TRIAL REGISTRATION 
9. 
GLOSSARY 
10. 
ATTACHMENTS TO THE INVESTIGATION PLAN 
11. 
BIBLIOGRAPHY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1. SYNOPSIS 
TITLE 
“Evaluation of the performance and safety of a Type I collagen-based 
medical device (MD-Small Joints Collagen Medical Device) in the 
treatment of rhizoarthrosis. "SMAGENART Pilot Study" 
STUDY DESCRIPTION  
Multicenter pilot study based on a One sample design. The variables 
will be assessed at 4 different time points: at baseline (time T0), after 
3 weeks (T3s), after 6 weeks (T6s), and after 16 weeks (T16s/FU), i.e., 
after 10 weeks from the end of the infiltrative treatment. 
OBJECTIVES 
The purpose of this research is to evaluate, using the Visual Analogue 
Scale (VAS), the performance of an intra-articular and peri-articular 
treatment with a collagen-based medical device in terms of pain 
reduction and joint function recovery in subjects affected by 
symptomatic rhizoarthrosis. The safety of the treatment will also be 
assessed. 
PRIMARY ENDPOINT 
The primary endpoint will consist of the evaluation, through the 
Visual Analogue Scale (VAS), of the performance of MD-Small Joints 
Collagen Medical Device in reducing pain associated with 
trapeziometacarpal osteoarthritis, at time T6 weeks (T6s) compared 
to T0. A reduction in VAS score of at least 30% is considered clinically 
significant. 
POPULATION 
A total of 42 subjects responding to the selection criteria will be 
progressively enrolled at the Clinical Investigation Centers involved. 
SELECTION CRITERIA 
Inclusion Criteria:  
• 
Male and female subjects aged between 18 and 75 years. 
• 
Subjects with clinically diagnosed symptomatic rhizoarthrosis 
confirmed radiographically (Stage I and II according to the 
classification of Eaton and Littler). 
• 
Subjects with a VAS score ≥ 5. 
• 
Subjects with joint pain for at least 1 month. 
• 
Subjects not using trapeziometacarpal orthotic devices. 
• 
Subjects who agree not to take analgesics within 24 hours 
before the scheduled visits. 
• 
Subjects capable of understanding and signing the Informed 
Consent.  

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Exclusion Criteria: 
• 
Subjects with rheumatological pathology involving the hands. 
• 
Subjects who have undergone surgery on the hand affected by 
pathology. 
• 
Subjects who have received HA infiltrations in the 
trapeziometacarpal joint in the last 3 months. 
• 
Subjects who have taken anti-inflammatory drugs in the last 7 
days and/or corticosteroids in the last 30 days. 
• 
Subjects undergoing physical therapy such as X-ray therapy, 
Tecar therapy, shock waves, laser therapy, ultrasound therapy 
in the last 3 months. 
• 
Subjects with neoplastic pathology. 
• 
Subjects with systemic infections. 
• 
Subjects with uncontrolled diabetes. 
• 
Subjects with neurological pathologies that may affect active 
participation in the study. 
• 
Subjects with coagulopathies or taking anticoagulants 
(vitamin K antagonists, heparin). 
• 
Subjects undergoing immunosuppressive therapy. 
• 
Subjects using drugs or abusing alcohol. 
• 
Subjects with allergy to porcine collagen. 
• 
Subjects who are pregnant or breastfeeding. 
• 
Subjects participating in other clinical studies during the same 
period. 
• 
Subjects unable to cooperate or for whom poor compliance is 
expected. 
• 
Any condition that, in the opinion of the investigator, 
recommends the subject's exclusion. 
STUDY PHASE 
Phase IV post market 
NUMBER OF SITE  
2 Clinical Investigation Centers 
DESCRIPTION OF THE  
INVESTIGATIONAL DEVICE  
The MD-Small Joints Collagen Medical Device is an injectable medical 
device composed of Type I porcine collagen. Each unit of the device 
contains 100µg of collagen per 2ml volume. 
DUR4ATION OF THE 
STUDY 
The entire clinical investigation will span over 8 months. It comprises 
a 4-month period for subject selection and recruitment, followed by a 

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4-month period for treatment and observation. 
DURATION OF THE STUDY 
FOR EACH SUBJECT 
The duration of the study for each subject will be 4 months. 
 
 
 
 
 
2. LISTA DELLE ABBREVIAZIONI 
 
 
AE 
Adverse Event 
ALP 
Abductor Pollicis Longus" 
DASH 
Disability of the Arm, Shoulder and Hand 
E-CRF 
"Electronic Case Report Form.’’ 
FIHOA 
Functional Index for Hand OsteoArthritis 
FU 
Follow Up 
GCP 
Good clinical practice 
HA 
Hyaluronic acid 
ICH 
International 
Council for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use 
LIM 
Intermetacarpal Ligament 
MD 
Medical Device 
SAE 
Serious Adverse Event 
TM 
Trapeziometacarpal Joint 
VAS 
Visual Analogue Scale 
 
 
 
 
 
 
 
 
 
 

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3. INTRODUCTION 
 
3.1 
Overview of the Functional Anatomy of the Trapeziometacarpal Joint 
 
The trapeziometacarpal joint (TM) can be considered a "saddle" or reciprocally interlocking joint, 
with movements primarily occurring in two planes: anterior/posterior movement on the sagittal plane 
and abduction/adduction on the frontal plane [1;2]. 
Additionally, the relatively lax joint capsule allows axial rotation of the metacarpal around its 
longitudinal axis [2]. This third degree of articulation enables thumb opposition movement in bi-
digital grips. The most significant movement is the pinch grip between the thumb and index finger, 
which can be distinguished as terminal, more refined and precise for securely grasping small objects, 
and sub-terminal, more recurrent and instinctive, where the thumb and index finger oppose with the 
palmar aspect of the fingertip and can grip objects of various sizes. In this latter grip, significant radial 
tension force is created on the metacarpal base, stretching the joint capsule and the intermetacarpal 
ligament over time, making them increasingly lax. This laxity results in joint instability, causing radial 
subluxation of the metacarpal and joint degenerative processes [1;3]. 
The genesis of rhizoarthritis lies precisely in TM instability, which can be primary or secondary 
(traumatic). In ligamentous laxity, instability is due to excessive range of motion, where the palmar 
ligament, limiting metacarpal hyperextension, and the intermetacarpal ligament (LIM), stretched 
between the base of the first and second metacarpal bones, which normally limits abduction 
movement of the first metacarpal bone, play a key role. Its relaxation is the basis for external 
subluxation of the base of the first metacarpal bone, leading to incongruity of the joint surfaces and 
initiating joint instability [2;3]. 
Another recognized and considered frequent cause is instability due to the absence of insertion of the 
abductor pollicis longus (APL) on the trapezium. In cases where the APL has a double distal insertion 
on the trapezium and the base of the first metacarpal bone, with each contraction of the APL, the entire 
thumb-metacarpal-trapezium column moves into abduction, maintaining normal trapeziometacarpal 
joint relationships. Conversely, if the insertion on the trapezium is absent, all abduction force is 
exerted on the base of the first metacarpal bone, causing significant subluxation tension with a 
deleterious effect on the TM cartilage [4]. 
3.2 
Osteoarthritis of the Trapeziometacarpal Joint 
The term rhizoarthritis refers to the arthritic process involving the TM joint. It is a condition that 
affects approximately 20% of the population over 50 years of age and is more common in females 
(ratio 4:1), typically manifesting around menopause. In 50% of cases, symptoms are bilateral [5; 6; 7]. 
The repeated grasping of small objects results in radial stress on the base of the first metacarpal bone, 

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with a significant increase in the destabilizing force transmitted at this level and progressive laxity of 
the capsulo-ligamentous apparatus [8; 9]. Consequently, joint laxity, altered load distribution, cartilage 
deterioration, and the onset of pain occur [1]. Disease progression is accompanied by a reduction in 
the strength of the thenar muscles and progressive subluxation of the TM joint, which in advanced 
stages can lead to complete dislocation of the base of the first metacarpal bone. As a compensatory 
phenomenon, the first ray metacarpophalangeal joint tends towards hyperextension in an attempt to 
preserve grip function: the thumb assumes a characteristic deformation called "Z-thumb" [12]. 
From a clinical standpoint, patients present with localized pain at the base of the thumb, exacerbated 
by active radial abduction and/or passive rotation-opposition movements [13], resulting in functional 
limitation and a decline in quality of life [10; 11]. 
The diagnosis of rhizoarthritis is clinical, confirmed by the presence of bone deformities and the 
above-described signs and symptoms. Radiographic examination allows instrumental staging of the 
disease. Eaton and Glickel first described a classification of the pathology based on the appearance of 
the joint in standard radiographic projections and under stress [14; 5]. The classification most 
commonly used today is the Eaton-Littler classification modified by Brunelli, which, in addition to the 
radiographic picture, also considers the clinical-functional aspect [5]. 
In the first stage of rhizoarthritis, treatment is usually conservative; in the second stage and early third 
stage, surgical treatment may be indicated using techniques for biological stabilization of the joint [3; 
15; 16]. In Eaton's third stage, prosthetic joint replacement may also be indicated, while in the fourth 
stage, the current trend is to perform a suspension arthroplasty surgical intervention [17]. 
 
Multiple alternatives have been proposed in the conservative management of symptomatic 
rhizoarthritis, with varying degrees of evidence and efficacy. These include: 
 
Orthoses: In a recent meta-analysis, orthosis use has been shown to be beneficial in reducing 
moderate/severe pain in the medium term (3-12 months) and improving function, and can avoid 
surgery in some patients [18; 19]. Additionally, they act as an insulating layer, which can help reduce 
worsening symptoms related to cold. For some patients, taping may be a good alternative [20]. 
Motor rehabilitation: Treatments performed by therapists experienced in hand pathology lead to 
significant improvement in pain and function [21]. Specific manual exercises help increase grip 
strength, reduce pain, and improve thumb joint mobility [22]. 
Pharmacological therapy: The American College of Rheumatology in 2012 and the European League 
against Rheumatism recommended the use of one or more of the following drugs for patients with 
hand osteoarthritis: topical capsaicin, oral NSAIDs, including selective COX2 inhibitors, and oral 
chondroitin sulfate. There is no literature evidence of the superiority of one specific anti-inflammatory 
treatment over another [23; 24]. 

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Infiltrative therapy: Corticosteroid injections into the trapeziometacarpal joint can result in pain 
reduction and functional improvement, but mainly in the short term and with significant side effects 
[25; 26; 27]. Hyaluronic acid injections represent an alternative to anti-inflammatory infiltrative 
therapy [28] and result in reduced resting pain with lasting benefit from 4 to 12 weeks [29]. 
3.3 Clinica Clinical Investigation Rationale 
Collagen is a structural protein biopolymer composed of three polypeptide chains wound together 
to form a right-handed triple helix. Its structure, characterized by the presence of glycine every third 
residue, a high content of proline and hydroxyproline, is stabilized by interchain hydrogen bonds and 
electrostatic interactions, which confer high mechanical strength, incompressibility, and, 
simultaneously, extensibility, plasticity, and flexibility to the molecules, making tissues abundant in 
collagen particularly resistant to stress and load [30]. 
In humans, collagen is particularly present in the skin, subcutaneous tissue, cartilage, bone, joint 
capsule, tendons, muscles, and ligaments [31; 32; 33]. Growing evidence supports the infiltrative use 
of type I collagen in the treatment of musculoskeletal pathologies [34]. In particular, the intra-articular 
and peri-articular use of collagen has been proposed in the treatment of osteoarthritis of various body 
districts with the aim of limiting joint hypermobility, stabilizing the structure of joint and peri-
articular components, reducing pain, and consequently improving function. Several clinical studies 
have demonstrated how its infiltrative intra-articular use, characterized by a series of 5 injections 
spaced one week apart, was able to determine pain reduction and improvement of functionality in 
different cases of knee and hip osteoarthritis [35; 36; 37; 38; 39]. Regarding the conservative 
management of symptomatic rhizoarthritis, some studies, although on limited case series, have shown 
how the use of type I collagen at the joint and peri-articular level in this condition is able to control 
painful symptoms, improve functionality, and reduce joint instability [40]. 
Recently, Randelli F. et al. studied the in vitro effects on tenocytes induced by type I porcine collagen 
(MD-Tissue Collagen Medical Device). In vitro results seem to demonstrate that this medical device 
can induce proliferation and migration of tenocytes and synthesis, maturation, and secretion of type I 
collagen, favoring tendon repair [41]. 
Randelli F. et al. also demonstrated the predominantly mechanical activity of MD-Tissue Collagen 
Medical Device, which is able to induce modifications of the morpho-functional properties of tenocytes 
[42]. 
In this Clinical Investigation, the performance and safety of use of an injectable medical device based 
on type I porcine collagen called MD-Small Joints Collagen Medical Device in the treatment of 
symptomatic rhizoarthritis will be investigated. 
 
4. SCIENTIFIC REQUEST 
 

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4.1 
Research Title 
"Evaluation of the Performance and Safety of a Type I Collagen-Based Medical Device (MD-Small 
Joints Collagen Medical Device) in the Treatment of Rhizoarthritis: The SMAGENART Pilot Study." 
 
4.2 
Research Objective 
The aim of this research is to evaluate, using the Visual Analogue Scale (VAS), the Disability of the 
Arm, Shoulder and Hand (DASH) questionnaire, the Functional Index for Hand Osteoarthritis (FIHOA) 
questionnaire, and the Pinch Strength Test, the performance of an intra-articular and peri-articular 
treatment with a collagen-based medical device in terms of pain reduction and recovery of joint 
function in subjects with symptomatic rhizoarthritis. The safety of the treatment will also be assessed. 
4.3 
Study Design  
This multicenter pilot clinical investigation will be based on a One Sample design. The variables will be 
assessed at 4 different time points: baseline (time T0), after 3 weeks (T3s), after 6 weeks (T6s), and 
after 16 weeks (T16s/FU), which is 12 weeks after the end of the infiltrative treatment. 
4.4 
Duration of Investigation  
The total duration of the investigation will be 8 months. It is expected that the selection and 
recruitment of subjects will take 4 months, followed by a treatment and observation period of 16 
weeks (Figure 1). 
 
 
Fig.1 Study Clinical Design 
 
4.5 
Participant Population 
A total of 42 subjects with thumb carpometacarpal osteoarthritis will be enrolled. The recruitment 
phase will not be closed until the number of subjects specified in the Clinical Investigation Plan is 
reached. 
Only subjects who meet the following criteria will be included: 
• 
Belonging to the Clinical Investigation Centers. 

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• 
Meeting the inclusion criteria and not presenting exclusion criteria. 
• 
Having dated and signed the Informed Consent. 
 
4.6 
Enrollment  
Enrollment will commence only after approval of the Clinical Investigation Plan by the relevant 
Territorial Ethics Committees and notification of the study to the Ministry of Health. 
Enrollment will involve subjects with thumb carpometacarpal osteoarthritis who are eligible 
according to the selection criteria. Diagnosis will be performed by the Principal Investigator of each 
Clinical Investigation Center through clinical and radiological examination. Eligible subjects will be 
briefed by the Principal Investigator or Co-Investigators on the rationale of the Clinical Investigation 
and the planned procedures. Consent to participate in the study will then be requested. 
4.7 
Selection Criteria 
4.7.1 
Inclusion Criteria: 
• 
Male and female subjects aged between 18 and 75 years; 
• 
Subjects with clinically diagnosed symptomatic thumb carpometacarpal osteoarthritis 
confirmed radiographically (stages I and II according to Eaton and Littler's classification); 
• 
[N.B. in case of bilateral symptomatic thumb carpometacarpal osteoarthritis, treatment can be 
unilateral only, at the level of the thumb carpometacarpal joint that is more affected at the time 
of enrollment]. 
• 
Subjects with a VAS score ≥ 5; 
[The request for pain intensity (VAS) from the patient should refer to moments of hand use, nota t rest!]  
 
• 
Subjects with joint pain for at least 1 month; 
• 
Subjects not using thumb carpometacarpal orthotic devices; 
• 
Subjects agreeing not to take analgesics within 24 hours before the scheduled visits; 
• 
Subjects capable of understanding and signing the Informed Consent. 
4.7.2 
Exclusion Criteria  
 
• 
Subjects with rheumatological conditions involving the hands; 
• 
Subjects who have undergone hand surgery for the affected pathology; 
• 
Subjects who have received HA injections in the thumb carpometacarpal joint in the last 3 
months; 
• 
Subjects who have taken NSAIDs in the last 7 days and/or corticosteroids in the last 30 days; 
• 
Subjects undergoing physical therapy such as X-ray therapy, Tecar therapy, shock wave 
therapy, laser therapy, ultrasound therapy in the last 3 months; 
• 
Subjects with neoplastic pathology; 

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• 
Subjects with systemic infections; 
• 
Subjects with uncontrolled diabetes; 
• 
Subjects with neurological conditions that may affect active participation in the study; 
• 
Subjects with coagulopathies or taking anticoagulants (vitamin K antagonists, heparin); 
• 
Subjects undergoing immunosuppressive treatment; 
• 
Subjects using drugs or abusing alcohol; 
• 
Subjects allergic to porcine collagen; 
• 
Female subjects who are pregnant or breastfeeding; 
• 
Subjects participating in other clinical studies during the same period; 
• 
Subjects unable to cooperate or for whom poor compliance is expected; 
• 
Any condition that, in the investigator's judgment, recommends the subject's exclusion. 
4.8 
Subject Coding 
Each Clinical Investigation Center will have a list containing the identification codes to be assigned 
to enrolled subjects. Since enrollment will be competitive, each list will contain 30 identification codes. 
At the time of enrollment, each subject will be sequentially assigned such an identification code. 
Lists with complex alphanumeric identification codes will be generated by GUNA S.p.a. through  
The complex alphanumeric code complies with the current Privacy Regulations regarding the 
coding of subjects participating in clinical studies. 
4.9 
Procedures 
4.9.1 
Evaluations of  Time Points 
Baseline (T0): Enrollment and initiation of infiltrative treatment. 
Week 1 (T1): Second infiltrative treatment. 
Week 2 (T2): Third infiltrative treatment. 
Week 3 (T3): 1st follow-up visit + fourth infiltrative treatment. 
Week 4 (T4): Fifth infiltrative treatment. 
Week 6 (T6): 2nd follow-up visit. 
Week 16 (T16)/FU: 3rd follow-up visit. 
4.9.2 
Visit Schedule 
Baseline (T0): Enrollment 
During routine clinical practice, the Investigators participating in the Clinical Investigation will 
select subjects diagnosed with symptomatic thumb carpometacarpal osteoarthritis. The Principal 
Investigator will be responsible for the correct clinical diagnosis, also utilizing the instrumental exams 
specified in the Investigation Plan. Subjects meeting the selection criteria will be identified. After 
thoroughly explaining the purposes, objectives, and procedures outlined in the Investigation Plan, the 
subject will be invited to participate in the Investigation. The selected subject will be invited to review 
the information sheet and date and sign the Informed Consent and Personal Data Processing Consent 

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form. Female subjects must provide evidence of a negative pregnancy test to be enrolled. The 
examination will then proceed, along with the collection of information required by the electronic Data 
Collection Form (e-CRF) appropriately prepared.  
This will be followed by: 
- 
VAS assessment; 
- 
DASH assessment; 
- 
FIHOA assessment; 
- 
Pinch Strength Test assessment using a dynamometer. 
 
The first intra/peri-articular infiltration of MD-Small Joints Collagen Medical Device (see § 4.12) will 
then be performed, evaluating any Adverse Events in the moments following administration. Any 
previous or ongoing pharmacological treatments of any kind (concomitant medications) will be 
documented in the annotations section of the e-CRF. During the study, systemic and topical analgesic 
medications may be used in case of severe pain. Investigators will explain to enrolled subjects that 
such medications should only be used if absolutely necessary and will provide each subject with 1 
package of oral analgesic medication and 1 package of topical analgesic medication among those 
permitted (see table 1), explaining the possible adverse events associated with intake or application 
and ensuring, under their responsibility, that the subject can take or apply the provided medication. To 
monitor its consumption, each subject will be given a clinical diary in which to record the day and dose 
of medication used, reminding them that such medications should not be taken or applied within 24 
hours before each visit. 
 
PERMISSIBBLE ORAL MEDICATIONS  
PERMISSIBLE TOPICAL MEDICATIONS 
Paracetamol 1000 mg. cpr. 
Diclofenac 2% gel 
Etoricoxib 60 mg. cpr. 
 
 
Tab. 1 Permissible topical analgesic medications 
 
The enrolled subject will be assigned a complex alphanumeric identification code. The collected data 
must be entered into the e-CRF within the following 48 hours. 
 
T1 settimana (±1gg): 
At one week from T0, the second intra/peri-articular infiltration of MD-Small Joints Collagen 
Medical Device will be performed (see § 4.12), and the use of the analgesic medication will be 
evaluated through the analysis of the clinical diary. Any adverse events occurring after the first 
administration will also be assessed. 

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T2 weeks (±1 day): 
At two weeks from T0, the third intra/peri-articular infiltration of MD-Small Joints Collagen 
Medical Device will be performed (see § 4.12), and the use of the analgesic medication will be 
evaluated through the analysis of the clinical diary. Any adverse events occurring after the second 
administration will also be assessed. 
 
T3 weeks (±1 day): 
At three weeks from T0, the fourth peri-articular infiltration of MD-Small Joints Collagen Medical 
Device will be performed (see § 4.12), and the use of the analgesic medication will be evaluated 
through the analysis of the clinical diary. The evaluation of VAS will be conducted. Any adverse events 
occurring after the third administration will also be assessed. The collected data must be entered into 
the e-CRF within the subsequent 48 hours. 
 
T4 weeks (±1 day): 
At four weeks from T0, the fifth and final peri-articular infiltration of MD-Small Joints Collagen 
Medical Device will be performed (see § 4.12), and the use of the analgesic medication will be 
evaluated through the analysis of the clinical diary. Any adverse events occurring after the fourth 
administration will also be assessed. 
 
6 weeks (±2 days): 
At six weeks from T0, and two weeks after the end of infiltrations, the following evaluations will 
be performed: 
- 
VAS assessment; 
- 
DASH assessment; 
- 
FIHOA assessment; 
- 
Pinch Strength Test evaluation using dynamometer; 
- 
evaluation of the use of analgesic medication through the analysis of the clinical diary; 
assessment of any adverse events occurring after the fifth administration. The collected data must be 
entered into the e-CRF within the subsequent 48 hours. 
T16 weeks/FU (±7 days): 
At four months from enrollment, and twelve weeks after the end of infiltrations, the following 
evaluations will be performed again: 
- 
VAS assessment; 
- 
DASH assessment; 
- 
FIHOA assessment; 

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- 
Pinch Strength Test evaluation using dynamometer; 
- 
evaluation of the use of analgesic medication through the analysis of the clinical diary; 
assessment of any adverse events occurring between T6s and T16s/FU. The collected data must be 
entered into the e-CRF within the subsequent 48 hours. 
The scales, questionnaires, and tests used to determine the performance of the medical device under 
investigation (VAS, DASH, FIHOA, and Pinch Strength Test) will be administered to the subject by the 
Principal Investigators or Co-Investigators. The recording of data from the clinical diary regarding the 
intake of analgesic medication will be carried out by them. 
In the e-CRF, the medications taken for the treatment of any co-morbidities that emerge during the 
Clinical Investigation must also be recorded. 
At each visit, the occurrence of Adverse Events will be carefully evaluated. All Adverse Events (AE) and 
Serious Adverse Events (SAE) appearing between the date of Informed Consent signature and the end 
of the Clinical Investigation will be recorded and reported. 
All data collected must be entered into the electronic Data Collection Form (e-CRF) provided by Guna 
S.p.a. Principal Investigators, Co-Investigators, or designated Data Managers will be responsible for the 
correct entry of the collected data into the e-CRF. 
In particular, it is expected to obtain a data collection that is schematically described in the following 
table (tab. 2), which lists the registrations to be made at each visit. 
 
 
EXPERIMENTAL PROCEDURES 
“SMAGENART PILOT STUDY” 
VISIT 
T0 
Enrollme
nt  
VISIT 
T1s. 
± 1day 
VISIT 
T2s. 
± 1day 
VISIT 
T3s. 
± 1day 
VISIT 
T4s. 
± 1day 
VISIT 
T6s. 
± 2day 
VISIT 
T16s/ 
FU 
± 7day 
Clinical diagnosis of rhizarthrosis 
confirmed radiographically 
X 
 
 
 
 
 
 
Evaluation of selection criteria 
X 
 
 
 
 
 
 
Sign Informed Consent 
X 
 
 
 
 
 
 
Sign Privacy Consent 
X 
 
 
 
 
 
 
Collection of socio-demographic data 
X 
 
 
 
 
 
 
Medical history collection 
X 
 
 
 
 
 
 
VAS assessment 
X 
 
 
X 
 
X 
X 
DASH assessment 
X 
 
 
 
 
X 
X 
FIHOA assessment 
X 
 
 
 
 
X 
X 
Pinch Strength Test Evaluation 
X 
 
 
 
 
X 
X 
Infiltrative treatment 
X 
X 
X 
X 
X 
 
 
Clinical diary evaluation of analgesic 
consumption. 
 
X 
X 
X 
X 
X 
X 
Concomitant treatment for ongoing 
X 
X 
X 
X 
X 
X 
X 

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comorbidities 
Adverse Event Assessment (AE/SAE) 
X 
X 
X 
X 
X 
X 
X 
 
Tab.2 Procedures and data collection during the Clinical Investigation  
 
4.10 
Material necessary for conducting the Clinical Investigation  
The medical device necessary to conduct the investigation is MD-Small Joints Collagen Medical 
Device (GUNA, Milan-Italy) marketed in 2ml vials.  
This device and the auxiliary drugs provided will be sent by Guna S.p.a. to the pharmacy of the Clinical 
Investigation Centers with shipment at a controlled temperature (range 4°-25°C) and monitored 
through dataloggers, in quantities suitable for conducting the Investigation.  
Medical devices and auxiliary drugs must be stored by the pharmacy of the Clinical Investigation 
Centers within the same temperature range. Each Clinical Investigation Center will be equipped with a 
datalogger provided by the Sponsor for temperature monitoring. 
The pregnancy tests will be sent, in suitable quantities, to the pharmacy of the Clinical Investigation 
Centers together with the medical devices and auxiliary drugs. 
4.11 
Group in the study  
The Investigation Plan envisages a single experimental group which will be treated with infiltrations 
of: MD-Small Joints Collagen Medical Device (GUNA, Milan-Italy). 
Composition per 2ml: collagen of porcine origin 100 µg 
Excipients: Violet, NaCl, Water for injection. 
The subjects will be treated with 1 infiltration with a volume of 2ml at the time of enrollment (T0) and 
on a weekly basis for a total of 5 infiltrations. 
4.12 
Infiltration Technique  
The infiltrations will be performed using 2.5ml syringes and 26 gauge/13mm needles under 
complete aseptic conditions. The first 3 infiltrations will be carried out at both intra- and peri-articular 
levels by injecting MD-Small Joints Collagen Medical Device into the trapeziometacarpal joint until a 
counter-pressure is felt, preventing further penetration of the liquid; the remaining quantity (usually 
about 1ml) will be injected at the peri-articular level by retracting the needle tip. 
The fourth and fifth infiltrations will be performed only at the peri-articular level. 
4.13 
Efficacy Criteria 
4.13.1 Primary Endpoint 
The primary endpoint will consist of evaluating, through the Visual Analogue Scale (VAS), the 
performance of MD-Small Joints Collagen Medical Device in reducing pain associated with 
trapeziometacarpal osteoarthritis at T6 weeks (T6s) compared to T0. A reduction in VAS score of at 
least 30% is considered clinically significant. 

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4.13.2 Secondary Endpoints 
The secondary endpoints will include evaluating the performance of MD-Small Joints Collagen 
Medical Device through: 
- 
VAS at T3s and T16s/FU compared to T0; 
- 
DASH at T6s and T16s/FU compared to T0; 
- 
FIHOA at T6s and T16s/FU compared to T0; 
- 
Pinch Strength Test at T6s and T16s/FU compared to T0; 
- 
Consumption of analgesics during various stages of the study; 
- 
Incidence of Adverse Events. 
 
4.13 
Data Collection   
All data resulting from the Clinical Investigation must be entered, within two days of their 
collection, into the electronic Data Collection Form (e-CRF) "Pheedit Dedagroup" provided by the 
Sponsor. Radiographic data will be collected and stored digitally on the hospital portal. Data entry 
procedures will be performed by the Principal Investigators, Co-Investigators, or the designated Data 
Manager. 
 
4.14 
Early Termination of the Investigation 
 
Subjects may terminate the Investigation prematurely for the following reasons: 
a. at their request (even without providing a reason); 
b. at the discretion of the investigator; 
c. if they experience an Adverse Event. 
The reason for termination will be recorded in the e-CRF. 
 
4 STATISTICS 
 
5.1 
Sample Size  
It is assumed that the fraction of subjects who will spontaneously reduce the VAS scale value by 
30%, given their clinical characteristics, cannot exceed 20% of those enrolled (null hypothesis: 
p_0≤0.2). Additionally, it is assumed that to consider the treatment with MD-Small Joints Collagen 
Medical Device clinically effective, the fraction of subjects who will reduce the VAS scale value by at 
least 30% should be at least 50% (alternative hypothesis: p_a≥0.5). 
With these assumptions, using a two-tailed binomial test, the sample size will be 33 subjects, with a 
power of 95.99% and an alpha error of 2.75%. Assuming that dropouts are approximately 20%, the 
number of subjects to be recruited will be approximately 42 (
33
(1−0.2) =
33
0.8 ≈42.  

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Incidentally, the null hypothesis can be rejected after obtaining 12 or more clinical successes, and the 
alternative hypothesis can be rejected with 1 or fewer clinical successes. 
 
 
 
 
 
 
 
5.1.1 
Statistical Analysis Plan 
5.1.2 
Descriptive Statistics 
All data will be validated according to appropriate rules based on their characteristics and then 
subjected to normal descriptive analyses (mean, median, mode, standard deviation, standard 
error of the mean, minimum and maximum values, interquartile range). Continuous variables 
with Gaussian distribution will be represented by mean ± standard deviation, while non-Gaussian 
variables will be represented by median and interquartile range. Categorical variables will be 
described using tables of relative and absolute frequencies. 
5.1.3 Primary Endpoint 
Tutti i dati saranno validati con delle opportune regole in base alle loro caratteristiche, e quindi 
sottoposti alle normali analisi descrittive (media, mediana, moda, deviazione standard, errore 
standard della media, valore minimo e massimo, range interquartile). Le variabili continue distribuite 
in modo Gaussiano saranno rappresentate da media ± deviazione standard, mentre quelle non 

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Gaussiane saranno rappresentate da mediana e range interquartile. Le variabili categoriche saranno 
descritte con tabelle di frequenza relativa ed assoluta. 
The primary endpoint will be determined by the fraction of enrolled subjects who reduce the VAS 
scale value by at least 30% after 6 weeks (T6s) from the start of treatment. The percentage fraction 
will be calculated with its 95% confidence interval according to Clopper-Pearson. 
5.1.4 Secondary Endpoints 
The secondary endpoints will consist of evaluating the performance of MD-Small Joints Collagen 
Medical Device through: 
- 
VAS at T3s and T16s/FU compared to T0; 
- 
DASH at T6s and T16s/FU compared to T0; 
- 
FIHOA at T6s and T16s/FU compared to T0; 
- 
Pinch Strength Test at T6s and T16s/FU compared to T0: using repeated measures ANOVA 
within subjects, or with the Friedman test, depending on the distribution of the data. 
- 
Consumption of analgesics in various stages of the study: through quantitative and qualitative 
counting of the drugs used. 
- 
Incidence of Adverse Events: as incidence and incidence rate for each individual type of 
Adverse Event and cumulatively for all. 
 
6 ETHICAL REQUIREMENTS 
6.1 
Ethical Authorizations 
Il Piano di Indagine Clinica sarà sottomesso ai Comitati Etici Territoriali di riferimento dei Centri di 
Indagine Clinica per l’espressione di parere. 
 
6.2 
Amendments to the Clinical Investigation Plan 
Qualsiasi modifica al presente Piano di Indagine sarà sottomessa dallo Sponsor, in forma di 
emendamento, ai Comitati Etici Territoriali di riferimento dei Centri Sperimentali per opportuna 
approvazione. 
 
6.3 
Subject Informationo 
The purposes and methods of the Investigation will be explained to each subject through an 
informative document (Informed Consent), containing what has been verbally explained by the 
clinician. The subject must personally date and sign the consent document. 
A copy of the document will be provided to the subject while the original will be kept by the 
investigator. 
No activity related to the Clinical Investigation can commence before the subject signs the Informed 
Consent. 

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6.4 
Adverse Events 
An Adverse Event is defined as any harmful clinical event that occurs during the Clinical 
Investigation in one of the subjects participating in the study population who has undergone the 
treatment specified by the Investigation Plan. 
Adverse events will be classified as serious (SAE) or non-serious (AE). 
An Adverse Event is defined as serious if (ICH-GCP DM 15/07/1997): 
• it results in the death of the subject involved in the Investigation; 
• it places the subject's life in jeopardy; 
• it requires hospitalization; 
• it requires prolonged hospitalization; 
• it results in permanent or temporary disability; 
• it results in a congenital anomaly or birth defect. 
In all other cases, the Adverse Event will be non-serious and will be classified as: 
• mild: does not interfere with normal daily activities and resolves spontaneously; 
• moderate: interferes with daily activities but resolves spontaneously; 
• serious: prevents daily activities and does not resolve spontaneously. 
All personnel participating in the study who come into contact with enrolled subjects must report 
Adverse Events communicated by the subjects to the Principal Investigator, who is responsible for 
collecting all possible data regarding them. 
 
Per Evento Avverso si intende qualsiasi evento clinico dannoso che si manifesterà nel corso 
dell’Indagine Clinica in uno dei soggetti che compongono la popolazione in studio che è stato 
sottoposto al trattamento previsto dal Piano di Indagine.  
Gli eventi avversi saranno classificati in serio (SAE) non-serio (AE). 
Un Evento Avverso viene definito serio se (ICH-GCP DM 15/07/1997): 
• 
provoca il decesso del soggetto coinvolto nell’Indagine; 
• 
pone il soggetto in pericolo di vita; 
• 
é tale da richiedere il ricovero in ospedale; 
• 
é tale da richiedere il prolungamento del ricovero ospedaliero; 
• 
é tale da provocare un’invalidità permanente o momentanea; 
• 
porti ad un’anomalia congenita o ad un difetto alla nascita. 
 
In tutti gli altri casi l’Evento Avverso sarà non-serio e verrà classificato in:  
• 
lieve non interferisce con le normali attività di vita quotidiane e si risolve spontaneamente;  
• 
moderato, interferisce con le attività di vita quotidiane ma si risolve spontaneamente;  

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• 
grave, impedisce le attività di vita quotidiane e non si risolve spontaneamente.  
 
Tutto il personale, partecipante allo studio, che viene a contatto con i soggetti arruolati deve riferire 
gli Eventi Avversi comunicati dagli stessi al Principal Investigator, il quale ha il dovere di raccogliere 
tutti i dati possibili in merito.  
 
All Adverse Events (AE) must be reported by the Principal Investigator to the Guna S.p.a 
Clinical Research Unit within 24 hours through telephone, email, specific form, and 
simultaneously through the e-CRF. AE must also be reported to the Pharmacovigilance Office of 
Guna S.p.a. 
Serious Adverse Events (SAE) must be reported to the Guna S.p.a Clinical Research Unit 
immediately (within 24 hours at most) by the Principal Investigator through telephone, email, 
specific form, and simultaneously through e-CRF. SAE must also be reported to the 
Pharmacovigilance Office of Guna S.p.a. These events will be promptly communicated to the 
Ethics Committee and the Ministry of Health. 
Guna S.p.a Clinical Research Unit: 
Tel: 02.28018358 / 02.28018359 
mail:  
v.miranda@guna.it 
k.laarej@guna.it 
clinical@guna.it 
Guna S.p.a Pharmacovigilance Office: 
Tel: 02.28018459 / 345.5884590 
mail:  
m.rossi@guna.it 
vigilanza@guna.it 
 
The Principal Investigator must implement all procedures to ensure the resolution of the event. In 
the case of Adverse Events (AE), it is necessary to consider that these may still give rise to Serious 
Adverse Events (SAE), which is why every Adverse Event must be monitored. Adverse Events not 
resolved at the end of the study will be followed up by the Investigators; every subject who has 
experienced an Adverse Event will be contacted at least once a month after the conclusion of the study 
for a number of months deemed appropriate. 

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6.5 
Privacy Protection 
The identities of the individuals involved will be known only to the Investigators and the Clinical 
Monitor responsible for monitoring the Investigation. Reference will be made to Regulation (EU) 
2017/745. 
Full respect for the anonymity of the subjects participating in the Investigation will be ensured. Data 
collection, processing, any scientific publications, or presentations at congresses of the results of the 
Clinical Investigation will be conducted in accordance with the current privacy regulations – 
Regulation (EU) 2016/679. 
6.6 
Data Access 
In compliance with the current regulations regarding Clinical Investigations on medical devices 
[Regulation (EU) 2017/745] and the Good Clinical Practice Guidelines (ICH/GCP), the Clinical 
Investigation Centers and Investigators will allow monitoring of the study according to the monitoring 
plan developed by the Sponsor. Furthermore, they will allow the Competent Authorities direct access 
to the documentation related to the study during audits. 
 
6.7 
Data Ownership 
All collected data will belong to Guna S.p.a. Milano, Italy, the Sponsor of the Clinical Investigation. 
Further information regarding data ownership is provided in the Contract. 
6.8 
Data Processing and Publication 
The results of this study will be summarized and presented in a final report aimed at drawing 
reliable conclusions regarding the performance of the injectable medical device MD-Small Joints 
Collagen Medical Device in the treatment of trapeziometacarpal osteoarthritis. The scientific article 
will then be drafted and submitted to a peer-reviewed journal in the field for publication to 
disseminate the obtained results to the scientific community. 
6.9 
Financing  
This research is funded by Guna S.p.a.  
For further information, please refer to the Contract. 
6.10 
Reference Ethical Code 
Reference is made to the Helsinki Declaration (Fortaleza 64th 2013), and the principles of Good 
Clinical Practice (GCP) (Legislative Decree 24 June 2003 – no.211 in G.U. no.184 of 09/08/2003) will 
be followed. 
6.11 
Subject Insurance 
For the entire duration of the Investigation project, insurance coverage will be provided by Guna 
S.p.a. for all enrolled subjects. 
 

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7 PREMATURE INTERRUPTION OF THE INVESTIGATION  
 
The Principal Investigators, reserve the right to prematurely terminate the Clinical Investigation at 
any time for reasonable medical and/or administrative reasons. The reasons for the interruption will 
be documented, and the Ethics Committees and the Ministry of Health will be informed of the decision. 
 
 
8 TRIAL REGISTRATION 
Guna S.p.a., Sponsor of the Clinical Investigation, will register the study on the Clinicaltrials.gov 
portal. 
 
9 GLOSSARY 
 
Medical device: any instrument, apparatus, implant, substance, or other article, whether used alone or 
in combination, including software, intended by the manufacturer to be used on humans for the 
purpose of diagnosis, prevention, monitoring, treatment, or alleviation of disease; diagnosis, 
monitoring, treatment, alleviation, or compensation for injury or disability; investigation, replacement, 
or modification of the anatomy or of a physiological process; intervention in conception, which does 
not achieve its principal intended action by pharmacological, immunological, or metabolic means, but 
which may be assisted in its function by such means. 
 
10 ANNEXES TO THE INVESTIGATION PLAN 
 
A. 
Informed Consent (information and consent)  
B. 
Consent for the processing of personal data (information and consent) 
C. 
Clinical Diary 
D. 
Visual Analogue Scale (VAS) 
E. 
Disability of the Arm, Shoulder and Hand (DASH) 
F. 
Functional Index for Hand OsteoArthritis (FIHOA) 
 
 
11 BIBLIOGRAPHY 
 
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