Clinical Trials Register

Summary
EudraCT Number:	2012-004890-25
Sponsor's Protocol Code Number:	BOLD01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2012-004890-25

A.3

Full title of the trial

Botulinum Toxin Serotype A randomized double-blind, placebo controlled multicentre study for degenerative coxarthrosis.

Studio randomizzato, multicentrico, in doppio cieco controllato con placebo sull'impiego di tossina botulinica di tipo A, nel trattamento della coxartrosi degenerativa.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Botulinum Toxin Serotype A randomized double-blind, placebo controlled multicentre study for degenerative coxarthrosis.

Studio randomizzato, multicentrico, in doppio cieco controllato con placebo sull'impiego di tossina botulinica di tipo A, nel trattamento della coxartrosi degenerativa.

A.3.2

Name or abbreviated title of the trial where available

BOLD

A.4.1

Sponsor's protocol code number

BOLD01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZIENDA OSPEDALIERO-UNIVERSITARIA S. MARIA DELLA MISERICORDIA DI UDINE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IPSEN S.P.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Az. Ospedaliero-Universitaria Udine
B.5.2	Functional name of contact point	SOC Neurologia
B.5.3	Address:
B.5.3.1	Street Address	P.le S. Maria della Misericordia 15
B.5.3.2	Town/ city	Udine
B.5.3.3	Post code	33100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0432-552720
B.5.5	Fax number	0432-552719
B.5.6	E-mail	neurologia@aoud.sanita.fvg.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	DYSPORT*SC IM 2FL 500U
D.2.1.1.2	Name of the Marketing Authorisation holder	IPSEN SpA
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BOTULINUM TOXIN TYPE A
D.3.9.1	CAS number	93384-43-1
D.3.9.4	EV Substance Code	SUB13117MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	TOSSINA BOTULINICA

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

coxarthrosis

coxartrosi

E.1.1.1

Medical condition in easily understood language

osteoarthrosis of the hip

artrosi dell'anca

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10028395
E.1.2	Term	Musculoskeletal and connective tissue disorders
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary efficacy variables will be the Harris Hip Score (HHS) at week 4.

Valutare l'efficacia della tossina botulinica sierotipo A 400 UI per migliorare (aumentare) il valore della scala Harris Hip Score (HHS) nei pazienti con osteoartrosi alla settimana 4 post-iniezione.

E.2.2

Secondary objectives of the trial

Secondary efficacy variables will be considered the following :
the Harris Hip Score (HHS) at week 2 and 12; the Subjective reporting of pain intensity (by a Visual Analogue Scale VAS) at week 2, 4, 12; the MRC scale (Scale to evaluate the muscular strength) and the SF-36 Quality of Life questionnaire. at week 2, 4, 12.

- Valutare la riduzione del dolore (scala analogica visiva, VAS) alle settimane 2, 4, 12.
- Valutare la forza muscolare (Medical Research Council scale, scala MRC) e valutare la qualità della vita nei pazienti (Short Form, SF-36) alle settimane 2, 4, 12.
- Valutare la modifica della Harris Hip Score (HHS) alla settimana 2 e 12
- Valutare la tollerabilità e la sicurezza del trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

All patients must fulfil the following criteria:

Subjects with primary or secondary symptomatic painful coxarthrosis, defined by radiographic signs (Rx or MRI or TC Scan) (see Table 1) and quantitative measurement of joint space
- Age between 18 - 80 years
- Written Voluntary Consent of the subject
- Impossibility of surgical treatment or elective surgery after six month to orthopaedic visit
- HHS > 20 (because in the previous study baseline HHS was 40 +/- 21)
VAS > 4 (minimal value defined as “significant pain”)

Coxartrosi di grado ≥ 1, definite in base alla classificazione di Kellgren-Lawrence (K / L) (vedi Tabella 1) VAS del valore> 4 Età tra i 18 - 80 anni Impossibilità di intervenire chirurgicamente causa comorbilità del paziente o possibilità di intervento chirurgico di protesizzazione non prima di 6 mesi in base alle indicazioni dell’ortopedico segnalante il caso. Firma del modulo di consenso informato del soggetto

E.4

Principal exclusion criteria

- Documented systemic allergy - Pregnancy
- Women who plan a pregnancy within six months of the treatment
- Previous treatment with BoNT/A, whatever the indication.
- Physiotherapy or articular injections with analgesic, hyaluronic acid or corticosteroids in the previous 60 days
- History of relevant central or peripheral neurological diseases.
-Patients subjected to a previous THA (total hip arthroplasty)
- In the opinion of the investigator the subject is unable and/or unwilling to comply fully with the protocol and the study instructions
- Apparent remission of coxarthrosis within 3 months- Subject who in the previous 4 weeks have made changes on analgesic oral therapy .

- Documentata allergia sistemica
- Gravidanza
- Le donne che pianificano una gravidanza entro sei mesi dal trattamento
- Un precedente trattamento con BoNT-A, qualunque sia l'indicazione.
- Iniezioni per fisioterapia o articolari con analgesico, acido ialuronico o corticosteroidi nei precedenti 60 giorni
- Storia di rilevanti patologie neurologiche centrali o periferiche.
- Pazienti sottoposti ad un precedente intervento di THA (protesi totale d'anca).
- Secondo il parere del ricercatore e/o del soggetto (incapacità a rispettare pienamente il protocollo e le istruzioni dello studio)
- La remissione apparente di coxartrosi entro 3 mesi precedenti
- Modifiche della terapia orale analgesica nelle 4 settimane precedenti

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variables will be the Harris Hip Score (HHS) at week 4.

end point di efficacia, valutazione del punteggio HHS a 4 settimane

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks

4 settimane

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

2, 4, 12 weeks

2, 4, 12 settimane

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2013-01-11.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

108

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

surgical treatment of hip osteoarthrosis or therapy with analgesic drugs

Protesizzazione d'anca quando indicato o terapia antalgica

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-01-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-04

P. End of Trial
P.	End of Trial Status	Completed

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